- lauraclark849
- Mar 24
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Updated: 6 days ago
Technical Review Article | Open Access | Published 26th March 2026
Biodegradable Polymeric Nanoparticles Based Drug Delivery Systems
Vibha Saxena¹,³*, Adarsh Kamble¹, Rushikesh Kejkar¹, Prathamesh Salunkhe¹, Sana Bagwan¹,
Rupesh Saknure¹, Hemant Swami³ https://doi.org/10.37521/ejpps31107
Abstract
Biodegradable polymeric nanoparticles have revolutionized the pharmaceutical industry by offering innovative drug delivery system alternatives. The therapeutic agents delivered by these materials result in non-toxic by-products during degradation which helps decrease environmental impact. Biodegradable nanoparticles reduce long-term body and environmental accumulation risks unlike traditional drug carriers thus supporting worldwide sustainability objectives & delivering ecological advantages. By delivering medications at controlled rates, these designed nanoparticles help minimize side effects while ensuring optimal therapeutic outcomes. Targeted medicines improve patient safety profiles and dosage schedules, which improves patient adherence and therapeutic results. As they can encapsulate drugs, which reduces systemic side effects and enhances therapeutic outcomes, they are safer and more effective for therapy. This study reviews the design concepts, manufacturing processes, and the therapeutic use of biodegradable polymeric nanoparticles in contemporary drug delivery systems., emphasizing how they have the potential to completely transform precision and customized medicine.
Keywords: Biodegradable, polymer, nanoparticles, drug delivery, tissue engineering, biocompatibility.
1 Introduction
Nanotechnology has grown in importance recently in a number of domains. Because of their "size effect," materials that range in size from 1 to 100 nm are referred to as nanostructured materials. Protein complexes, membranes, and viruses are examples of biological systems that are naturally occurring nanostructures. Consequently, materials at the nanoscale can be used in biomedical devices.¹
The medication enclosed in Nanoparticle matrix, can yield Nanospheres, or Nano capsules. Nanospheres serve as matrix structures where the drug is evenly and physically distributed, On the other hand, Nanocapsules are vesicular systems. where a unique synthetic membrane encloses a cavity that contains the drug.² Biodegradable polymers that are both natural and artificial have a number of benefits, including low toxicity, tissue compatibility, biodegradability, prolonged release, and targeted delivery methods.³,⁴. Nanocapsules and Nanospheres are both considered "nanoparticles," however they differ in their form.⁵ Biodegradable sutures, which were initially authorized in the 1960s, were the first of many applications for polymers in the medical field.⁶ As biodegradable polymeric biomaterials, manufactured and biologically produced polymers have both been thoroughly studied. Polymer erosion results from the breaking of enzymatic or hydrolytically sensitive linkages in polymeric biomaterials during biodegradation Depending on the degradation process, polymeric biomaterials can be further classified as hydrolytically or enzymatically degradable polymers. The majority of ring polymers found in nature degrade enzymatically⁷.
Biodegradation is the natural process by which organic substances are broken down into simpler molecules and mineralized through elemental cycles such as carbon, nitrogen, and sulphur. This occurs only within the biosphere, as microbes are essential to the process.⁸ Recent decades have seen rapid growth in the study of polymer nanoparticles (PNPs), with applications in photonics, electronics, sensors, biotechnology, medicine, environmental technology, pollution control, and nanotechnology across textiles, agriculture, forensic science, and space research. Biodegradable polymers, which can be either natural (e.g., polysaccharides, collagen, silk, soy, fibrin gels) or synthetic, degrade mainly through enzymatic or chemical pathways linked to living organisms.⁹,¹⁰,¹¹,¹²,¹³,¹⁴ The degradation typically involves two stages: initial abiotic or biotic reactions such as oxidation, hydrolysis, or microbial activity that reduce polymers to smaller molecular species, followed by further breakdown. These polymers are increasingly recognized as sustainable alternatives to petrochemical-based materials, with potential to support green energy initiatives and reduce CO₂ emissions.¹⁵,¹⁶
In vivo, biodegradable polymers retain their characteristics for a short period of time before gradually breaking down into soluble or digestible chemicals released out of the body. In order for these frameworks to be utilized for in vivo applications, the polymers used must possess the best qualities possible in terms of shelf life, sterilizing capacity, process ability, and biocompatibility. It is essential to evaluate the characteristics of the system (drug and particle) for every application and drug in order to ascertain whether a particular formulation is the most efficient for a given drug delivery application.¹⁷ Biodegradable nanoparticles efficiently transport the medication to the intended location, maximizing therapeutic value and reducing adverse effects. However, they give pharmacologically active substances a controlled release at the designated location at the ideal pace and dosage.¹⁸
2.PREPARATION OF BIODEGRADABLE NANOPARTICLES (NPs)
Biodegradable polymeric nanoparticles can be fabricated using various approaches. Their formulation may involve the direct use of a macromolecule or a pre-synthesized polymer or alternatively require a polymerization process. Traditionally, two major strategies have been employed for nanoparticle preparation:
2.1 Dispersion of the preformed polymers,
2.2 Monomer polymerization
2.1 Dispersion of preformed polymers
PLGA (Poly (lactic-co-glycolic acid), PLA (Polylactic acid), poly(e-caprolactone), and PLG (Poly D, L-glycolide) can be converted into biodegradable nanoparticles using a variety of techniques.¹⁹
2.1.1 Solvent evaporation method
Solvent evaporation was the first method developed to manufacture polymeric NPs from a synthesized polymer. In this technique, making an oil-in-water (o/w) emulsion is the initial stage. ²⁰ This procedure involves dissolving the polymer in an organic solvent, such as dichloromethane, Ethyl acetate or chloroform, to create Nanospheres. The medication is dissolved or dispersed into the prepared polymer solution to form an oil (O) in water (W), or O/W, emulsion. A surfactant or emulsifying agent, such as gelatin, poly (vinyl alcohol), polysorbate-80, poloxamer-188, etc., is then used to emulsify this combination into an aqueous solution. The organic solvent is removed by raising the temperature, applying pressure, or stirring constantly after a stable emulsion has formed. ²¹ The water-soluble drug-loaded NPs have also been made using the W/O/W technique.²² Both of the above listed methods make use of high-speed homogenization or sonication. Nonetheless, these methods work well at the laboratory level, but new techniques utilizing low-energy emulsification are needed for a large-scale pilot production. The following strategies have been tried in this quest.
2.1.2 Solvent diffusion method
By combining an aqueous solution of the drug with a surfactant and a somewhat water-miscible solvent that contains a polymer and medication, this technique produces an o/w emulsion.²³,²⁴ An organic solvent that is somewhat hydro-miscible, like benzyl alcohol or ethyl acetate, and has been saturated with water to establish a preliminary thermodynamic equilibrium between the internal phase of this emulsion is composed of the two phases at room temperature. ²⁵ Colloidal particles are created as a result of solvent dilution entering the exterior phase from the scattered droplets caused by the following dilution with a significant volume of water. This process is typically used to create Nanospheres, but it is also possible to create Nanocapsules by adding a small quantity of oil to the organic phase, such as triglycerides C6, C8, C10, and C12. Finally, this last step can be removed by filtration or evaporation, depending on the organic solvent's boiling point. ²⁶. NPs having dimensions between 80 and 900 nm can ultimately be obtained. The solvent diffusion method is extensively applied for the fabrication of polymeric nanoparticles. However, it requires the elimination of a considerable volume of aqueous medium, as there is a risk of hydrophilic drug diffusion from the colloidal system into the external aqueous phase. ²⁷,²⁸
2.1.3 Salting out method
The emulsification/reverse salting-out technique can be combined with the emulsification/solvent fusion technology previously mentioned. The salting-out strategy is based on the separation. extracting a solvent that is hydro-miscible from an aqueous solution utilizing the salting-out phenomena, which may lead to the formation of Nanospheres. ²⁹ The main distinction is that the aqueous phase consists of a gel, a colloidal substance, whereas the o/w emulsion is composed of a water-miscible polymer solvent such as ethanol or acetone. salting-out agent and stabilizer. ³⁰ Examples of suitable salting-out agents include electrolytes such as magnesium chloride (MgCl2), calcium chloride (CaCl2), or magnesium acetate [Mg(CH3COO)2], as well as non-electrolytes like sucrose. ³¹ When the aqueous phase is saturated, acetone and water become less miscible, allowing the other miscible phases to mix to form an o/w emulsion. ³². The o/w emulsion is made at room temperature while being vigorously swirled to enable the organic solvent to diffuse to the outer phase, the polymer to precipitate, and ultimately the creation of Nanospheres. After that, a suitable volume of deionized water or aqueous solution is added to dilute it. The residual cross-flow filtering removes the salting-out agent and solvent. Although it is not necessary, the organic solvent and water must be completely miscible for the process to function. ²⁹
2.2 Polymerization of monomers
Another possibility is that monomers are polymerized to create nanoparticles. ³¹ There are two ways to encapsulate vaccines or medications in nanoparticles: first, the drug is dissolved in the polymerization solution; second, the therapeutic agent is adsorbed or conjugated onto the polymerized and generated nanoparticles. By eliminating stabilizers, the obtained nanoparticle suspension is refined. The utilized surfactants are recyclable for subsequent polymerization. ³³ This process for creating biodegradable polymeric nanoparticles is easy and efficient. ³⁴ This method requires evaluating the impact of variables such as the amount of monomer used in polymerization, the kind of surfactant, and the concentration of organic solvent. ³⁵
3.CLASSIFICATION OF BIODEGRADABLE POLYMERS
3.1 NATURAL BIODEGRADABLE POLYMER
These polymers are typically found in nature in the form of plants and animals and include cellulose, proteins, starches, resins, etc.³⁶
Polysaccharides
Cellulose
Cellulose is a polysaccharide composed of D-glucose units arranged in a linear chain. These glucose units are linked together by condensation reactions through β-glycosidic bonds. ³⁷ Enzymatic breakdown of polymers into D-glucose units is possible using glycoside hydrolases. Studies have been conducted on it as a hydrogel base, drug delivery matrix, and wound dressing. ³⁸,³⁹. About 150 years ago, cellulose was first isolated. in certain ways, cellulose is different from other plant-produced polysaccharides. Its lengthy molecular chain is made up of a single repeating unit called cellobiose. It is found in a crystalline form. Cellulose is chemically extracted in micro fibrils from the cell walls. N-methyl morpholine-N-oxide (NMMO) is one of the most powerful solvents capable of dissolving cellulose, a high-molecular-weight, highly crystalline polymer that is otherwise resistant to breakdown. Since cellulose is insoluble and infusible, it is usually converted into derivatives to facilitate its processing [40]. Furthermore, certain bacteria secrete endo- and exo-enzymes, some of which act synergistically to form complexes that enable cellulose degradation and the production of carbohydrates essential for microbial survival. ⁴¹,⁴².
Starch
One type of polymer that is found in many plants is starch. Rice, corn, and potatoes are the main crops utilized to produce it. Granules of starch are produced by all of these plants however their sizes and compositions differ slightly. Since traditional film-forming resins are becoming more expensive and harder to get, starch has gained popularity as a raw material in the filmmaking industry. ⁴³.For many years, starch has been added to plastic for a variety of uses. Starch was added to a number of resin technologies to create water-vapour-permeable yet water-impermeable films. In LDPE, it was used as a biodegradable filler. ⁴⁴,⁴⁵,⁴⁶.Starch's ease of processing makes it suitable for a number of additional uses, such as a fibre, a porous matrix, and a film forming. ⁴⁷,⁴⁸.Granules of starch with size varying from 1 to 100 µm are isolated from a various plant tissues. ⁴⁹ Granules vary in size and shape depending on where they come from. ⁵⁰ Amylose and amylopectin are two polysaccharides found in starch. Depending on source of the starch, the proportion of these two polysaccharides varies. It also contains proteins and lipids, but in trace amounts.⁵¹.
Alginic Acid (AA)
It is possible to extract the naturally occurring anionic polysaccharides, also referred to as algin or alginates, derived from the cell walls of several bacterial strains, Laminaria hyperborea, and Ascophyllum nodosum, as well as brown algae. ⁵² A naturally occurring hydrogel, alginate extract is derived from brown algae that are present in the ocean. The Phaeophyceae family, which includes a variety of seaweeds, is mainly made up of multicellular algae. ⁵³.These species are comparable to cement because of their abundance and gel-like quality. They work well as polymers, fillers, binders, and viscosity enhancers because of their thickening and gelling properties. This property may serve as an epoxy primer to cement concrete and other composite materials together. ⁵⁴. The fresh alginate is made from Sargassum plagyophyllum biopolymers, which are frequently utilized in commercial applications, and comes in gel, fiber, and powder form.⁵⁵
Protein
Collagen
This has numerous biomedical uses and can originate from humans as well as several other species, horses, bovines, and pigs. Fibroblasts are the cells that produce collagen, and they often come from reticulum cells or pluripotent adventitial cells.⁵⁶,⁵⁷. The (ECM) extracellular matrix of many tissues contains the structural protein collagen, which is widely distributed in human body. It is composed of triple-helix-shaped polypeptide chains that provide tissues with their remarkable mechanical qualities and durability. ⁵⁸. The human body contains collagen which comes in about twenty-two varieties, with Type I–IV being the most prevalent. The most prevalent protein found in mammals and the one that has been investigated the most is type I collagen. ⁵⁹. The body uses enzymes such as collagenases and metalloproteinase to break down collagen enzymatically and produce the necessary amino acids. ⁶⁰.
Gelatin
A blend of proteins and peptides known as gelatin is created when collagen has been partially hydrolyzed from cooked bones, organs, connective tissues, and guts of some animals. Collagen hydrolyzes irreversibly to generate gelatin, which is made up of single-strand molecules that have lost their original triple-helix shape. ⁶¹. The primary protein present in fish, bones, and connective tissue is collagen. It can be hydrolysed by enzymes, acids, or alkalis to create this product. While Type B gelatin is made by treating a process with an alkali, Type A gelatin is made by treating a precursor with acid. ⁶²,⁶³. For biomedical projects, it is a preferred choice because it is biocompatible and biodegradable in physiological settings and when it comes into contact with living tissues. ⁶⁴.
Albumin
Albumin is the most prevalent globular protein belonging to the albumin family. Albumins are not glycosylated like other blood proteins, which is why they are frequently detected in blood plasma. Materials termed albuminoids include albumins, such egg white. ⁶⁵,⁶⁶. The molecular weight of albumin is 66 k Dalton, making it a water-soluble protein. Transporting hydrophobic fatty acids is albumin's primary function in maintaining blood pH and the presence of acid molecules in the blood. ⁶⁷. The FDA has also authorized albumin-based surgical adhesives for reattaching the layers of major vessels, including the carotid, femoral, and aortic arteries. They consist of albumin from bovine serum, gelatin, and glutaraldehyde. ⁶⁸.
3.2 SYNTHETIC BIODEGRADABLE POLYMERS
Synthetic polymers are fibres that are created in a lab by polymerizing basic chemical components. Synthetic polymers include Teflon, PVC, synthetic rubber, nylon, polyethene, and polystyrene, among others.
Polyesters
Poly (α-hydroxy acids)
This polyester family's excellent biocompatibility and variable degrading properties have led to the most research into its potential for use in biomedical applications. The base was established by them. Polyglycolide was used to create the first synthetic suture material. Depending on the initial monomer units, either ring opening or condensation polymerization is used to create these polymers. ³⁸,⁶⁹,⁷⁰. The matrix's porosity, crystallinity, and polymer molecular weight all affect how quickly things break down. It degrades more slowly than polyglycolide because it is more hydrophobic. ⁷¹,⁷²,⁷³.
Polylactones
The semi crystalline polymer polycaprolactone (PCL) is easily processed since it dissolves in ordinary solvents. It breaks down due to hydrolytically labile ester linkages. By altering the rate of decomposition and further characteristics, polycaprolactone's potential for a variety of uses is increased by copolymer blends and combinations with macromers, low molecular weight polyols, and other polymers.⁷⁰,⁷⁴,⁷⁵. Poly (p-dioxanone), another polylactone, was utilized to make the first monofilament suture in the 1980s. An extremely low Tg semi crystalline polymer that ranges from roughly 10°C to 0°C. ⁷⁶,⁷⁷.
Poly(anhydrides)
Poly(anhydrides) are surface-eroding polymers that Langer and associates created for drug delivery applications. ⁷⁸,⁷⁹. Injection moulding or compression moulding can be used to create delivery systems for poly(anhydrides). If injection moulding is utilized, the amine groups on a drug may react with the anhydride bond with readily denatured proteins since it demands temperatures greater than room temperature.⁸⁰. After thorough testing of the material's biocompatibility and release of drugs both in vivo and in vitro, the US FDA authorized it as a pharmaceutical delivery device in 1996.⁸¹. Polyanhydrides experience erosion that results in a linear mass loss, which leads to their general classification as surface eroding polymers. Still, research has demonstrated that their disintegration occurs beyond the surface of the polymer matrix, and further research has attempted to clarify additional factors influencing polyanhydride degradation. ⁸²,⁸³.
Poly (amino acids)
Numerous biological applications have been extensively studied due to the structural resemblance of this family of polymers to real proteins. But because of their poor mechanical properties and immunogenicity, these polymers changed into pseudo-amino acid polymers. Amino acid-based polymers were created by copolymerizing amino acids with other monomers and grafting amino acids onto synthetic polymers, employing amino acid sequences and PEG to create building block copolymers, and producing pseudo poly (amino acids). Examples of non-amide bonds that bind amino acids together to create the pseudo poly (amino acids) include carbonates, esters, and immuno-carbonates. ⁸⁴,⁷⁰,⁸⁵ .
Polyphosphazenes
They are of the class of inorganic polymers that have two supporting groups connected to both sides of phosphorus atoms of a backbone made up of nitrogen and phosphorus atoms. Since its successful synthesis, poly dichlorophosphazene has been utilized as a starting point for the substitution procedure to create various polyphosphazenes. Alkoxide, aryloxide, and other groups were used to substitute the Cl group in poly (dichlorophosphazene) due to the high reactivity of the P–Cl bond. They become biodegradable when groups such as glyceryl units, lactate, amines, glucosyl, and amino acid esters are substituted on phosphorus. ⁸⁶,⁸⁷. Hydrolytically stable phosphorus and nitrogen make up the backbones of the more than 500 distinct types of polyphosphazenes have been created to date. ⁸⁸.
3.3 MICROBIAL BIODEGRADABLE POLYMERS
Poly hydroxy alkanoates
A type of intracellular biopolymer, these granules store energy and carbon and are made by a variety of bacteria. They are made up of β-hydroxy fatty acids, where the R group is tridecyl instead of methyl. PHB, or polyhydroxybutyrate, is the primary PHA family biopolymer. This PHB was utilized to create several copolymers, including poly (hydroxybutyrate-co-hydroxyoctanoate) and poly(hydroxybutyrate-co-hydroxyvalerate). ⁸⁹.
Poly (γ-glutamic acid)
Through microbial fermentation, this anionic, water-soluble, biodegradable polymer is created. In reality, different proportions of D and L-glutamic acid make up this copolymer. There are several forms of amide links that use β- and γ-carboxylic groups in addition to ε-amino groups, and α-amide connections between α-amino and γ-carboxylic acid groups are known to exist. A thermosensitive polymer, scaffolds for tissue engineering applications, and a drug delivery system (Taxol is provided using the covalent immobilization technique) have all been studied thus far. Poly (glutamic acid) and gelatin have been used to make surgical adhesives and haemostasis. ³⁸,⁸⁵,⁹⁰
4. BIODEGRADATION (MECHANISM OF ACTION)
Natural elemental cycles like the C, N, and S cycles cause organic compounds in the environment to spontaneously decompose into smaller molecules, mineralize, and redistribute. this process is known as biodegradation. Because microorganisms are essential to the biodegradation process, biodegradation can only take place within the biosphere. ⁹¹.
There are two phases to this process. First, the polymers discontinue into lower subatomic mass species due to either biotic (such as microbial corruption) or abiotic (such as oxidation, photo degradation, or hydrolysis) reactions. ⁹²
An irreversible alteration in the physico-chemical properties, and visual appearance of a polymer resulting from the chemical breakage of its constituent macromolecules by one or more mechanisms is known as polymer degradation. ⁹³ External circumstances can cause multiple mechanisms to operate simultaneously, and at any given time, one mechanism may be more prominent than the others. ⁹⁴. Acidic or alkaline conditions, heat, humidity, and radiation are examples of external environmental factors that can change the pace of degradation. The degradation process can change the mechanical, optical, and electrical qualities of polymers, as well as their colour, wear, cracking, crazing, and phase separation or de-lamination. ⁹³. The four primary abiotic processes linked to the breakdown of polymers are hydrolytic (chemical), mechanical, thermal (or thermo-oxidative), and photo oxidative. Catalysis can also help with some of these processes. Furthermore, ozone degradation (chemical) is regarded as a polymer degradation mechanism, albeit it is less frequent. Enzymatic activity by microorganisms is a component of biotic degradation.
4.1 ABIOTIC DEGRADATION
Mechanical degradation
Mechanical degradation occurs when a polymer is exposed to a harsh environment or mechanical forces, resulting in the decline in mechanical characteristics that manifests in the performance of the polymer. When a polymer is subjected to shear, tension, and/or compression, mechanical deterioration may result. Although mechanical forces don't usually play a significant part in the biodegradation process, they can cause harm before microorganisms activate or speed up the process. [95] Polymeric materials subjected to mechanical stress, like biomaterials in the medical profession, frequently undergo mechanical degradation as a result of loading while in use.¹⁵ However, physical forces including heating, cooling, wetting, and drying, in addition to water or air-induced surface turbulence, can lead to mechanical deterioration because to stress cracking. ⁹⁴. For example, there is a connection between mechanical and biotic deterioration when assessing the rate at which biodegradable films degrade in industrial settings and many films in agricultural environments. ⁹⁶. The scientific literature commonly reports the even if these characteristics can be an addition to biodegradation monitoring rather than the best ones, loss of mechanical qualities as a sign of the final biodegradation process. The primary results of mechanical degradation are the reduction of hardness, impact resistance, tensile and flexural characteristics. ⁹⁵,⁹⁷,⁹⁸
Thermal degradation
When a polymer is heated for an extended length of time, it undergoes thermal degradation, sometimes referred to as thermo-oxidative degradation at oxygen (O2). As heat degradation begins, macromolecular connections are broken, releasing radicals or monomeric units that can react with oxygen to create peroxide radicals. ⁹⁷
Thermal degradation causes distinct alterations in the polymer structure depending on the thermal energy and exposure duration: (1) Thermal breakdown occurs when the structure of the polymer is altered at temperatures lower than the glass transition point, leading to physical aging. (2) Changes include the loss of dimensions and original shape, crystallization processes, and the thermal degradation of low molecular weight (MW) additives. (3) At temperatures higher than Tm, the crystalline region loses its structure, resulting in chaotic melt and loss of structure. (4) At temperatures significantly above the breakdown temperature, the material burns, and energy can be recovered. ⁹⁸. (5) Four distinct reactions that can happen simultaneously make up thermal degradation, which happens throughout the polymer's bulk. (6) cyclic and linear oligomer recombination processes, such as PLA (7) randomly generated chain scission that lowers. (8) deterioration due to replacement procedures. (9) volatile compounds produced by C-C bond chain-end scission or chain depolymerisation. ⁹⁷,⁹⁹
At high temperatures, thermal degradation dominates because its rate is faster than that of mechanical, light, and hydrolysis degradation. On the other hand, it can cause the polymer to age at temperatures below Tg, increasing the process of biodegradation efficiency.
Thermal degradation of biodegradable polymers takes place in the melting temperature range, which encompasses temperatures much higher than the range where the biodegradation process mostly takes place. The Tm for PLA and PHB is approximately 155 ◦C and 175 ◦C, respectively, suggesting that heat degradation will not impact or quicken the biodegradation process. Thermal degradation can actively engage in the biodegradation process because Tm
for certain thermoplastic polymers, such as PCL, is in the vicinity of the thermophilic range. ⁹⁵ By increasing mobility, the energy can change the arrangement of macromolecules and enhance the biodegradation process. reorganization and creation of polymeric chains' free volume ⁹⁵
Photo degradation
When in contact with gamma radiation, infrared (IR), visible and ultraviolet (UV) spectra, polymers can degrade both photo degradative and radiationally. Photo degradation, which can occur with or without oxygen (photolysis) or with oxygen present (photo oxidative degradation), leads to reorganization cross-linking and chain scission. the wavelengths of visible light, UV light, and infrared (IR) radiation present in sunshine are linked to the level of photo degradation. The radiation that reaches the earth's surface has wavelengths that vary from from UV-C to infrared, or 295 to 2500 nm. ¹⁰⁰
Because of electron activation at higher energies, polymers that absorb a lot of UV light are prone to oxidation and cleavage. ⁹³,¹⁰¹ In addition to breaking polymer chains and producing radicals, photo degradation can alter physical and optical characteristics, cause a yellowing effect, cause mechanical capabilities to be lost, and lower MW, all of which can result in a worthless content. ⁹⁷,¹⁰²
Chemical degradation
With the exception of polytetrafluoroethylene (PTFE) and polyether ketone (PEEK), most polymers can be impacted by the chemical breakdown of corrosive gases and liquids. Most polymers will be attacked and degraded by ozone, air pollutants (including sulphur and nitric oxides), and acids like sulphuric, nitric, and hydrochloric.¹⁰³
4.2 BIOTIC ENZYMATIC DEGRADATION
The process by which bacteria break down organic molecules using enzymatic processes is known as "biotic enzymatic degradation." The primary result of biotic degradation is the disintegration of the polymer structure into tiny molecules that the bacteria consume as a source of carbon and energy. When aerobically conducted, this process yields final compounds such as H2O and CO2. Fungi and bacteria are examples of microorganisms that actively take part in the biodegradation process. Because these microbes have unique development requirements, biotic degradation is a complicated process involving a number of variables related to the polymer, microbes, and environment. ¹⁰⁴.
4.3 FACTORS THAT INFLUENCE BIODEGRADATION
Polymer structure impact
Common macromolecules in organic frameworks are usually harmed by hydrolysis and oxidation. Thus, it is not unexpected that a sizable portion of the intended biodegradable polymers that have been reported include hydrolysable bonds along the polymer chain; for instance, hydrolytic proteins and microbes are unable to biodegrade amide enamine, esters, urea, or urethane links. Because the majority of compound-catalysed reactions take place in fluid conditions, they are hydrophilic. The biodegradability of synthetic polymers is greatly influenced by their characteristics. Polymers with a combination of hydrophobic and hydrophilic components appear to be more biodegradable than those with only hydrophobic or hydrophilic structures. ¹⁰⁵.
Effect of polymer morphology
The short repeating units found in most synthetic polymers promote crystallisation and prevent enzymes from accessing the hydrolysable groups. Long repeating units in synthetic polymers were believed to have a lower crystallization rate and so be possibly biodegradable. In fact, it was demonstrated that subtilisin could easily break down a number of poly (amide-urethane) polymers. ¹⁰⁶
Radiation and chemical therapy effects
The production of particles and/or radicals by UV photolysis and Ô-beam illumination of polymers frequently results in cleavage and cross-linking. Additionally, oxidation takes place, which makes matters more difficult because light exposure might occasionally happen without oxygen. This mostly makes the material more vulnerable to biodegradation. The observed rate of debasement is originally expected to increase until most of the divided polymer has been consumed, at which point the rate of corruption of the cross-linked component of the polymer should be slower. This was corroborated by a study on how UV irradiation affects hydrolysable polymers. ¹⁰⁷ As expected, ray exposure significantly affects the rate at which polyesters degrade in vitro. Oxidation of polyalkenes by photo exposure encourages (in most situations, marginally) the biodegradation. ¹⁰⁸,¹⁰⁹
Other factors include
Unexpected units or chain flaws are present.
Structure of configuration.
Conditions of processing
Annealing,
Sterilisation procedures
Storage history
Shape
Implantation site
Absorbed and adsorbed substances (such as ions, lipids, and water)
Physical-chemical elements (pH, ionic strength, and ion exchange)
Physical elements (diffusion fluctuations, changes in size and shape)
Coefficients mechanical stresses cracking caused by solvents and stress, etc.
The hydrolysis mechanism (water versus enzymes). ⁹².
5. RECENT DEVELOPMENTS IN BIODEGRADABLE POLYMERIC NANOPARTICLES
First half table:
Polymer Types | Formulated Drug | Method | Applications | Reference |
PLC, PLA, PLGA | Coumarin | Solvent displacement technique | Drug delivery, Microplastic detection | [110] |
AcDex | Hyperforin | Single emulsion solvent evaporation technique | Drug delivery, vaccine development, and antitumor therapy | [111] |
EudragitⓇ L100 | Fenofibrate | solvent displacement | Enteric Coating, Controlled Release | [112] |
PCL, PLGA | Ciprofloxacin | Solvent displacement | Sustained release, Targeted delivery, Bone infections | [113] |
PEG-PPG | Curcumin | Double emulsion/multiple emulsion method | Anticancer | [114] |
PEG | Pegademase bovine | PEGylation method | To treat severe combined immunodeficiency disease (SCID) in children | [115] |
PCL-PEG | Paclitaxel | Ring-opening polymerization method | Management of one of the most dangerous and common diseases called ovarian cancer | [116] |
PLGA-PEG | Paclitaxel | Nanoprecipitation method | Drug delivery system used to treat cancer | [116] |
Eudragit® RS100, Eudragit® L100-55, Eudragit® | Volatile oils | Solvent displacement | Food, cosmetics, pharmaceuticals, and aromatherapy | [117] |
PLGA Poly (lactic-co-glycolic acid) | Taxol | Solvent removal / liquid-liquid extraction (LLE) | To treat cancer, particularly for cancers like ovarian, breast, and lung cancer | [118] |
PLGA Poly (lactic-co-glycolic acid) | Paclitaxel | Interfacial deposition method | Drug delivery system for cancer treatment, particularly for cancers like ovarian, breast, and lung cancer | [119] |
PLGA Poly (lactic-co-glycolic acid) | Taxol | Nanoprecipitation | Drug delivery system for cancer treatment, particularly for cancers like ovarian, breast, and lung cancer | [120] |
PLGA Poly (lactic-co-glycolic acid) | Oestradiol | Emulsion diffusion | Treating symptoms of menopause, osteoporosis, and other condition | [121] |
PLGA Poly (lactic-co-glycolic acid) | 9-Nitrocamptothecin | Nanoprecipitation | Drug delivery, anticancer drug | [122] |
PLGA Poly (lactic-co-glycolic acid) | Xanthones | Solvent displacement technique | Cancer therapy, drug delivery, vaccination | [123] |
PLGA Poly (lactic-co-glycolic acid) | Docetaxel | Emulsion solvent diffusion | Anticancer drug | [124] |
PLGA Poly (lactic-co-glycolic acid) | Thymopentin | Double emulsion solvent evaporation method | Delivery of drugs | [125] |
PLGA Poly (lactic-co-glycolic acid) | Dexamethasone | Solvent evaporation method | Otology, Sensor functionality, Anti-inflammatory | [126] |
PLGA Poly (lactic-co-glycolic acid) | Rapamycin | Emulsification diffusion method | Osteoarthritis (OA) Treatment | [127] |
PLGA Poly (lactic-co-glycolic acid) | Fenofibrate | Direct membrane emulsification | To treat ischemic stroke | [128] |
PLGA Poly (lactic-co-glycolic acid) | Curcumin | Solvent evaporation, Nanoprecipitation | Antibacterial activity, pancreatic cancer | [129] [130] |
PLA (Polylactic acid) | Haloperidol | Solvent removal | Treat nervous, emotional and mental condition | [131] |
PLA (Polylactic acid) | Haemoglobin | Double emulsion method | To create artificial red blood cells (RBCs) | [132] |
PLA (Polylactic acid) | Dexamethasone | Spray drying | Ophthalmology, Wound healing, Arthritis treatment, Cancer treatment | [133] |
PLA (Polylactic acid) | Ellagic acid | Emulsion diffusion evaporation method | Antioxidant activity, Improved thermal stability, UV protection | [134] |
PLA (Polylactic acid) | Protein-C | Double emulsion method | Anticoagulant function | [135] |
PLA (Polylactic acid) | Zidovudine | Solvent evaporation | Treatment HIV, combination therapy | [136] |
PLA (Polylactic acid) | Oridonin | Modified SESD method | Anti-inflammatory, antibacterial | [137] |
PLA (Polylactic acid) | Neurotoxin-I | Double emulsions or multiple emulsions | To smooth dynamic wrinkles | [138] |
PLA (Polylactic acid) | Savoxepine | Salting out | Drug delivery | [139] |
PLA (Polylactic acid) | Progesterone | Solvent evaporation | Used in various contraceptive preparation to prevent ovulation and fertilization | [140] |
Second half of Table:
PCL (Poly-caprolactone) | Tamoxifen | Solvent displacement | Targeted delivery, enhanced efficacy, control release | [141] |
PCL (Poly-caprolactone) | Clonazepam | Solvent evaporation method | To treat certain type of seizures | [142] |
PCL (Poly-caprolactone) | Saquinavir | Solvent displacement method | To treat human immunodeficiency virus (HIV) infection | [143] |
PCL (Poly-caprolactone) | Taxol | Micelles | As a drug delivery system | [144] |
PCL (Poly-caprolactone) | Docetaxel | Nanoprecipitation method | Drug delivery, tumour targeting | [145] |
PCL (Poly-caprolactone) | Vinblastine | Emulsion method | To treat breast cancer, neuroblastoma, mycosis fungoides | [146] |
PCL (Poly-caprolactone) | Amphotericin B | Solvent displacement | To treat serious and potentially life-threatening fungal infections | [147] |
Gelatin | Paclitaxel | Desolvation method | To treat cancer | [148] |
Gelatin | Didanosine | Double desolvation technique | Treatment of HIV infection | [149] |
Gelatin | Chloroquine phosphate | Solvent evaporation method | To prevent and treat malaria | [150] |
Gelatin | Insulin | Ionotropic gelation method | Drug delivery, diabetes treatment | [151] |
Chitosan | Cyclosporin A | Ionic gelation method | Improve drug delivery, topical treatment | [152] |
Chitosan | Ammonium glycyrrhizinate | Ionic gelation method | Anti-inflammatory skin care, Acne treatment, wound healing, sun protection, | [153] |
Table 1: Drug components loaded in Polymeric nanoparticles
6. APPLICATIONS AND CHALLENGES OF BIODEGRADABLE POLMERS
6.1 Industry
Biodegradable polymers are extensively utilized due to their great heat resistance, waterproof characteristics, resistance to chemical erosion, dirt resistance, and potent colouring power to produce leather, fibre, and packaging film. In particular, packaging films that decompose naturally are gaining more and more attention. Poly-ε-caprolactones (PCL), It is widely applicable as an eco-friendly substance, are easier to find and less expensive than other biodegradable polyesters. Pullulan, starch, chitosan, and other biopolymers based on polysaccharides have been studied and employed as packaging films. Packing goods and disposable items can be made from poly-3-hydroxybutyrate (PHB), another biodegradable polymer ¹⁵⁴
6.2 Biomaterial
A range of polymers have been employed in clinical examinations, therapeutic procedures, and preventative medicine. When employed directly with living cells in our bodies for medical purposes, a particular class of polymers is referred to as polymeric biomaterials. Disposable items (such as syringes, blood bags, and catheters), surgical aids (like stitches, sealants, and adhesives), tissue replacement devices (such as dental, breast, and intraocular implants), and artificial organs for either short-term or long-term support (like vascular grafts, artificial kidneys, and artificial hearts). are typical uses of biomaterials in medicine. Biodegradable medicinal polymers have garnered a lot of interest. This new trend can be attributed to at least two factors.
6.3 Therapeutics and Clinical Practice
A variety of polymers have been used in clinical examinations, therapeutic procedures, and preventative medicine. One class of polymers, known as polymeric biomaterials, is used directly with living cells in our bodies for medical purposes. Some common applications of biomaterials in medicine include tissue replacement prostheses, surgical aids, and disposable items like syringes, blood bags, and catheters; surgical aids, such as sutures, adhesives, and sealants; and artificial organs for short-term or long-term assistance, such as vascular graft, prosthetic heart, and artificial kidney.
6.4 Pharmacy and Medicine
The three key features of biodegradable polymers as biomaterials are biocompatibility, biological absorbability, and mechanical resistance, which makes them most suitable to use in pharmacy and medicine. Biodegradable polymers are mostly utilized in orthopaedic surgery, tissue engineering, absorbable sutures, and as medication release agents. PLA, PHB, etc. have been extensively employed as drug carriers in drug-releasing delivery systems. In order to create absorbable sutures that can naturally break down and When wounds heal, PGA, PLA, and their copolymers are used by the organisms that absorb them. One promising material for bone and cartilage restoration is polybutylene succinate.¹⁵⁵
6.5 Dental Care
It has been established that chitin and chitosan help prevent excessive scarring, speed up wound healing, and produce an attractive skin surface. Additionally, chitin/chitosan is utilized in dentistry as a bandage for oral mucosal ulcers and as a tampon after receiving extensive therapy for maxillary sinusitis. Additionally, its potential as an absorbent membrane in periodontal surgery is being investigated. Chitin and chitosan are touted as a wholesome food that might aid because of their diverse biological functions, treat and/or improve a number of illnesses, including hepatitis, diabetes, cancer, arthritis, and more.
6.6 Surgical Sutures
A fractured bone or a deep incision in soft tissue are examples of tissue injury that cause a loss of structural integrity and may not be able to heal on their own without assistance. The healing process could be aided by the implantation of a substance or tool to hold the tissue together. The sutures used to keep superficial and severe wounds together are classic examples. The suture becomes unnecessary when the healing process is finished and may put the healing tissues under unwelcome restrictions. Removing the substance from the place, either physically or through degradation, is desirable. Since their development in the 1960s, synthetic absorbable sutures have become popular in both general and tracheobronchial surgery due to their high biocompatibility with tissues. Since their development in the 1960s, synthetic absorbable sutures have become popular in tracheobronchial surgery and general surgery due to their high biocompatibility with tissues surgery.
They are sutures of the multifilament kind, which are manageable. The most widely used and currently marketed substances are polyglycolide (PGA), polylactin, poly-l-lactide (PLA) and its copolymers, and polyglactin are the substances in question. However, braided sutures with uneven surfaces are useless for continuous suturing. Sutures made of monofilament have flat surfaces and can be used continuously When it comes to monofilament sutures PLA and PGA are too rigid and unyielding. Due to their lower bending moduli, polydioxanones and polyglyconates are more pliable and suitable for use as sutures. For possible clinical applications, bioabsorbable elastic materials like copolymers of l-lactide and e-caprolactone-poly (CL-LA) have also been investigated. ¹⁵⁶
6.7 Grafts of the Vascular System
A lot of research has been done to create vascular prostheses with small diameters that are acceptable. Small-diameter vascular prostheses with integrated matrices are designed to be incorporated into the developing neointima at the anastomotic site. It was demonstrated that a compound of heparin and gelatin, when sufficiently cross-linked, might serve as both a great substructure for an anastomotic neointima and a transient antithrombogenic surface. ¹⁵⁷
6. CHALLENGES IN THE BIOMEDICAL APPLICATION OF POLYMERIC
NANOPARTICLES
Some of the common challenges with nanoformulations are illustrated in Figure 7. Due to the nano size formulation excessive aggregation or degradation of nanoparticles could lead to stability challenges. BPNP’s entrapment efficiency and release kinetics are always based on the environmental factors which play a part in drug efficacy. Hydrophilicity or lipophilicity of drug helps to decide on the route of administration of nanoformulations along with physiological interference. High Dose, poor solubility, bioavailability, toxicity and cost are the other factors that need consideration before commercialization. The repeatability of the procedure used to create nanoparticles is another problem. It is still difficult to produce uniform nanoparticles on a large scale. There are few research articles that address the BPNPs’ in vitro properties, and future scope for in vivo research is still there, to enhance the drug encapsulation capacity of BPNPs.¹⁵⁸
Conclusion
Biodegradable polymers, particularly in the form of nanoparticles, have revolutionized various fields, including drug delivery, biomedical applications, and environmental sustainability. Their ability to control drug release, enhance bioavailability, and reduce toxicity makes them an essential component in modern pharmaceutical formulations. Additionally, their role in agriculture, industry, and medicine highlights their versatility and growing significance. Despite some limitations, ongoing research and advancements in polymer technology continue to enhance their functionality, making them a promising solution for future biomedical and environmental challenges.
References
1. Xu T, Zhang N, Nichols HL, Shi D, Wen X. Modification of nanostructured materials for biomedical applications. Mater Sci Eng C 27 (3): 579-594, 2007.
2. Kumaresh S. Soppimath, Tejraj M. Aminabhavi, Anandrao R. Kulkarni,Biodegradable polymeric nanoparticles as drug delivery devices,Walter E. Rudzinski b
3. Mir M, Ahmed N, ur Rehman A. Recent applications of PLGA based nanostructures in drug delivery. Colloids and Surfaces B: Biointerfaces. 2017;159:217-31
4. Tsai C-H, Wang P-Y, Lin I, Huang H, Liu G-S, Tseng C-L. Ocular drug delivery: Role of degradable polymeric nanocarriers for ophthalmic application. International journal of molecular sciences. 2018;19(9):2830
5. Scha azick, S.R.; Pohlmann, A.R.; Dalla-Costa, T.; Guterres, S.l.S. Freeze-drying polymeric colloidal suspensions: Nanocapsules, nanospheres and nanodispersion. A comparative study. Eur. J. Pharm. Biopharm. 2003, 56, 501–505.
6. J. C. Middleton, A. J. Tipton,Synthetic biodegradable polymers as orthopedic devices, Biomaterials 2000, 21, 2335
7. Katti DS, Lakshmi S, Langer R, Laurencin CT. Toxicity, biodegradation and elimination of polyanhydrides. Adv Drug Deliv Rev 2002;54:933–61
8. R. Chandra, Renurustgi, Biodegradablepolymers Department of Polymer Technology and Applied Chemistry, Delhi College of Engineering
9. Schmid G. Nanoparticles: from theory to applications. Weinheim, Germany: Wiley-VCHPublishers;2004.
10. Zhang Q, Chuang KT. Adsorption of organic pollutants from effluent so fakraftpulpmillonactivatedcarbonandpolymerresin.Adv EnvironRes2001; 5:251–8.
11. I. Perelshtein, et al., Sonochemical coating of silver nanoparticles on textile fabrics (nylon, polyester and cotton) and their antibacterial activity, Nan otechnology 19 (2008) 245705
12. B.Speiser,Nanoparticlesinorganicproduction?in:IssuesandOpinions,16th IFOAMOrganic World Congress, Modena, Italy, 2008.
13. Reis, R.L.; Cunha, A.M.; Allan, P.S.; Bevis, M.J. Mechanical be havior of injection-molded starch-based polymers. Polym. Adv. Technol., 1996, 7, 784-90.
14. Mohanty, A.K.; Misra, M.; Hinrichsen, G. Biodegradable polymers and biocomposites: An overview. Macromol. Mater. Eng., 2000, 276-277, 1-24.
15. Lucas, N.; Bienaime, C.; Belloy, C.; Queneudec, M.; Silvestre, F.; Nava-Saucedo, J.E. Polymer biodegradation: mechanisms and estimation techniques. Chemosphere 2008, 73, 429-442.
16. Narayan R (2001) Drivers for biodegradable/compostable plastics and role of composting in waste management and sustainable agriculture. Orbit J 1(1):1–9
17. Meredith L (2005) Hans Synthesis, characterization, and application of biodegradable polymeric prodrugs micelles for long-term drug delivery Doctor of Philosophy page no 8 A Thesis Submitted to the Faculty of Drexel University.
18. Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE. Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release 70: 1-20, 2001
19. . Vauthier, S. Beanabbou, G. Spenlehauer, M. Veillard, P. Couvreur, Methodology of ultradispersed polymer system, S.T.P. Pharm. Sci. 1 (1991) 109–116.
20. Desgouilles, S.; Vauthier, C.; Bazile, D.; Vacus, J.; Grossiord, J.-L.; Veillard, M.; Couvreur, P. The design of nanoparticles obtained by solvent evaporation: A comprehensive study. Langmuir 2003, 19, 9504–9510
21. P.D. Scholes, A.G.A. Coombes, L. Illum, S.S. Davis, M.Vert, M.C. Davies, The preparation of sub-500 nm poly(lactide co-glycolide) microspheres for site-specific drug delivery, J. Control. Rel. 25 (1993) 145–153.
22. M.F. Zambaux, F. Bonneaux, R. Gref, P. Maincent, E. Dellacherie, M.J. Alonso, P. Labrude, C.Vigneron, Influence of experimental parameters on the characteristics of poly(lac tic acid) nanoparticles prepared by double emulsion method, J. Control. Rel. 50 (1998) 31–40.
23. Kumar,S.;Dilbaghi,N.; Saharan, R.; Bhanjana, G. Nanotechnology as Emerging Toolfor EnhancingSolubility of Poorly Water-Soluble Drugs. BioNanoScience 2012, 2, 227–250.
24. Souto, E.B.; Souto, S.B.; Campos, J.R.; Severino, P.; Pashirova, T.N.; Zakharova, L.Y.; Silva, A.M.; Durazzo, A.; Lucarini, M.; Izzo, A.A.; et al. Nanoparticle Delivery Systems in the Treatment of Diabetes Complications. Molecules 2019, 24, 4209.
25. Souto,E.B.; Severino, P.; Santana, M.H.A. Preparação de nanopartículas poliméricas a partir da polimerização de monômeros: Parte I. Polímeros 2012, 22, 96–100.
26. Guterres, S.S.; Alves, M.P.; Pohlmann, A.R. Polymeric nanoparticles, nanospheres and nanocapsules, for cutaneous applications. Drug Target Insights 2007, 2, 117739280700200002.
27. Quintanar-Guerrero,D.; Allemann,E.; Doelker, E.; Fessi, H. Preparation and characterization of nanocapsules from preformed polymers by a new process based on emulsification-di usion technique. Pharm. Res. 1998, 15, 1056–1062.
28. Vasile, C. Polymeric Nanomaterials in Nanotherapeutics; Elsevier: London, UK, 2018.
29. Wang,Y.; Li, P.; Truong-Dinh Tran, T.; Zhang, J.; Kong, L. Manufacturing techniques and surface engineering of polymer based nanoparticles for targeted drug delivery to cancer. Nanomaterials 2016, 6, 26.
30. Lim, K.; Hamid, Z.A.A. 10—Polymer nanoparticle carriers in drug delivery systems: Research trend. In Applications of Nanocomposite Materials in Drug Delivery; Inamuddin, Asiri, A.M., Mohammad, A., Eds.; Woodhead Publishing: Cambridge, UK, 2018; pp. 217–237.
31. Reis,C.P.; Neufeld, R.J.; Ribeiro, A.J.; Veiga, F.; Nanoencapsulation, I. Methods for preparation of drug-loaded polymeric nanoparticles. Nanomed. Nanotechnol. Biol. Med. 2006, 2, 8–21
32. Vauthier, C.; Bouchemal, K. Methods for the preparation and manufacture of polymeric nanoparticles. Pharm. Res. 2009, 26, 1025–1058.
33. Mahapatro A, Singh DK. Biodegradable nanoparticles are excellent vehicle for site directed in-vivo delivery of drugs and vaccines. J Nanobiotech 9 (1): 55, 2011.
34. Zhang Y, Zhuang X, Gu W, Zhao J. Synthesis of polyacrylonitrile nanoparticles monomer concentrations by AIBN-initiated semi continuous emulsion polymerization method. Eur Polym J 67: 57-65, 2015
35. Puglisi G, Fresta M, Giammona G, Ventura CA. Influence of the preparation conditions on poly(ethylcyanoacrylate) nanocapsule formation. Inter J Pharm 125: 283-287, 1995.
36. Saripilli Rajeswari, Teella Prasanthi, Navya Sudha, Ranjit Prasad Swain1 Satyajit Panda and Vinusha Goka, NATURAL POLYMERS: A RECENT REVIEW, WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES, 2017, Volume 6, Issue 8, 472-494.
37. Sindhu Doppalapudia,Anjali Jaina, Wahid Khana,b and Abraham J. Dombb, Biodegradable, polymers—an overview, Special issue: Review,2014,1-9.
38. L. S. Nair, C. T. Laurencin, Tissue Engineering I. Springer, Verlag Berlin Heidelberg, 2006, 102, pp. 47.
39. D. Klemm, B. Heublein, H. P. Fink, A. Bohn, Angew. Chem. Int. Ed. 2005, 44, 3358.
40. R.Chandra, Renurustgi, Biodegradable polymers,Prog.Polym.Sci.,Vol.23,1273–1335,1998.
41. Liungdahl, K. E. Erisksson, in Advances in Microbial Ecology, Vol. 8, ed. K. C. Marshall. Plenum, New York, 1985, p. 237.
42. Aubert, J. P., Beguin, P. and Millet, J., Biochemistry and Genetics of Cellulose Degradation. Academic, New York, 1988.
43. Otey, F. H., Westhoff, R. P. and Russell, C. R., Ind. Eng. Chem. Prod. Res. Dev., 1977, 16, 305.
44. Shulman, J. and Howarth, J. T., US Patent No. 3,137,664, 16 June 1964.
45. Griffin, G. J. L., Am. Chem. Soc. Div. Org. Coat, Chem. Soc. Div. Org. Coat. Chem, 1973, 33 (2), 88.
46. Griffin, G. J. L. and Turner, R. D., International Biodeterioration Conference, Berlin, 1978.
47. D. Lu, C. Xiao, S. Xu, Express Polym. Lett. 2009, 3, 366.
48. K. Pal, A. Banthia, D. Majumdar, Afr. J. Biomed. Res. 2006, 9(1), 23–29.
49. Sugih, A.K., Picchioni, F., Janssen, L.P.B.M. And Heers, H.J. 2009. Synthesis of poly-(epsilon)-caprolactone grafted starch co-polymers by ring-opening polymerization using silylated starch precursors. Carbohydr. Polym. 77, 267–275
50. BUCKNOW, R., JANKOWIAK, L., KNORR, D. and VERSTEEG, C. 2009. Pressure–temperature phase diagrams of maize starches with different Amylose contents. J. Agr. Food Chem. 57, 11510–11516.
51. LIU, H., XIE, F., YU, L. and CHEN, L. L.I., L., 2009a. Thermal processing of starch-based polymers. Prog. Polym. Sci. 34, 1348–1368.
52. Szekalska, M.; Puciłowska, A.; Szymańska, E.; Ciosek, P.; Winnicka, K. Alginate: Current Use and Future Perspectives in Pharmaceutical and Biomedical Applications. International Journal of Polymer Science 2016, 2016, 1-17,
53. K. Venkataraman, M. Wafar, Coastal and marine biodiversity of India, Indian J. Mar. Sci. 34 (1) (2005) 57–75,
54. R.M.I.R. Susilorini, H. Hardjasaputra, S. Tudjono, G. Hapsari, S.R. Wahyu, G. Hadikusumo, J. Sucipto, The advantage of natural polymer modified mortar with seaweed: Green construction material innovation for sustainable concrete, Procedia Eng. 95 (2014) 419–425,
55. E. Anwar, H. Erianto, K.S.S. Putri, Preparation of powder from brown seaweed (Sargassum Plagyophyllum) by freeze-drying with maltodextrin as a stabilizer, Int. J. Appl. Pharm. 10 (2018) 348–353.
56. W. Friess,Collagen--biomaterial for drug delivery, Eur. J. Pharm. Biopharm. 1998, 45, 113.
57. W. Khan, D. Yadav, A. J. Domb, N. Kumar, Biodegradable Polymers in Clinical Use and Clinical Development 2011, 59–89, DOI: 10.1002/ 9781118015810.
58. Moncal, K.K., Ozbolat, V., Datta, P., Heo, D.N., Ozbolat, I.T., 2019. Thermally-controlled extrusion-based bioprinting of collagen. J. Mater. Sci. Mater. Med. 30.
59. Altman GH, Diaz F, Jakuba C, Calabro T, Horan RL, et al. Silk based biomaterials. Biomaterials 2003;24:410–6.
60. Vin F, Teot L, Measume S. The healing properties of Promogran in venous leg ulcers. J Wound Care 2002;11: 335–7.
61. Kiran Sharma, Vijender Singh, Alka Arora, Natural Biodegradable Polymers As Matrices In Transdermal Drug Delivery, International Journal of Drug Development & Research, April-June 2011 | Vol. 3,10.
62. C.-H. Chang, H.-C. Liu, C.-C. Lin, C.-H. Chou, F.-H. Lin, Biomaterials 2003, 24, 4853.
63. D. Ledward, G. Phillips, P. Williams, Handbook of hydrocolloids. CRC Press, 2 nd Edition, 2000, 67, DOI: 10.1002/9780470988701.
64. Ofokansi K, Winter G, Fricker G, Coester C (2010) Matrix-loaded biodegradable gelatin nanoparticles as new approach to improve drug loading and delivery. Eur J Pharm Biopharm 76(1):1–9.
65. F. Kratz, J. Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles,Control Release 2008, 132, 171
66. M. Roche, P. Rondeau, N. R. Singh, E. Tarnus, E. Bourdon,The antioxidant properties of serum albumin, FEBS letters 2008, 582, 1783.
67. Prinsen BH, de Sain-van der Velden MG. Albumin turnover: experimental approach and its application in health and renal diseases. Clin Chim Acta 2004;347(1–2):1–14.
68. Lakshmi S. Naira, Cato T. Laurencina, Biodegradable polymers as biomaterials, Prog. Polym. Sci. 32, (2007) 762–798.
69. P. A. Gunatillake, R. Adhikari,Biodegradable synthetic polymers for tissue engineering,Eur. Cell. Mater. 2003, 5, 1.
70. P. Gunatillake, R. Mayadunne, R. Adhikari,Recent developments in biodegradable synthetic polymers, Biotechnol. Annu. Rev. 2006, 12, 301.
71. R. A. Auras, L. T. Lim, S. E. Selke, H. Tsuji, Poly (lactic acid): synthesis, structures, properties, processing, and applications, Vol. 10. Wiley, Hoboken, New jersey, 2011.
72. B. Gupta, N. Revagade, J. Hilborn,Poly(lactic acid) fiber: An overviewProg. Polym. Sci. 2007, 32, 455
73. A. J. Lasprilla, G. A. Martinez, B. H. Lunelli, A. L. Jardini,Poly-lactic acid synthesis for application in biomedical devices — A review, Biotechnol. Adv. 2012, 30, 321.
74. V. Chiono, G. Vozzi, M. D’Acunto, S. Brinzi, C. Domenici, F. Vozzi, A. Ahluwalia, N. Barbani, P. Giusti, G. Ciardelli,Characterisation of blends between poly(ε-caprolactone) and polysaccharides for tissue engineering application, Mater. Sci. Eng. C 2009, 29, 2174
75. M. Dasaratha Dhanaraju, D. Gopinath, M. Rafiuddin Ahmed, R. Jayakumar, C. Vamsadhara, Characterization of polymeric poly(ϵ-caprolactone) injectable implant delivery system for the controlled delivery of contraceptive steroids, J. Biomed. Mater. Res. A 2006, 76, 63.
76. Q. Li, J. Wang, S. Shahani, D. D. Sun, B. Sharma, J. H. Elisseeff, K. W. Leong,ROS-responsive selenium-containing polyphosphoester nanogels for activated anticancer drug release, Biomaterials 2006, 27, 1027.
77. K.-K. Yang, X.-L. Wang, Y.-Z. Wang, J.Nonisothermal crystallization behaviour of poly(ρ-dioxanone) and poly(L-lactic acid) blends, Macromol. Sci., Polym. Rev. 2002, 42, 373.
78. Linhardt, R., Rosen, H., and Langer, R. (1983) Bioerodable polyanhydrides for controlled drug delivery. Polym. Prepr. 24, 47-48.
79. Ron, E., Turek, T., Mathiowitz, E., Chasin, M., Hageman, M., and Langer, R. (1993) Controlled release of polypeptides from polyanhydrides. Proc. Natl. Acad. Sei. U.S.A. 90,4176-4180
80. Leong, K., D’Amore, P., Marletta, M., and Langer, R. (1986) Bioerodible polyanhydrides as drug carrier matrices. I. Biocompatability and chemical reactivity. J. Biomed. Mater. Res. 20, 51-64.
81. Katti DS, Lakshmi S, Langer R, Laurencin CT. Toxicity, biodegradation and elimination of polyanhydrides. Adv Drug Deliv Rev 2002;54:933–61.
82. Akbari H, D’Emanuele A, Attwood D. Effect of geometry on the erosion characteristics of polyanhydride matrixes. Int J Pharm 1998;160:83–9.
83. Shieh L, Tamada J, Tabata Y, Domb A, Langer R. Drug release from a new family of biodegradable polyanhydrides. J Contr Rel 1994;29:73.
84. M. Hacker, A. Mikos, Foundations of Regenerative Medicine: Clinical and Therapeutic Applications. Academic press, London, 2009, 336.
85. L. S. Nair, C. T. Laurencin,Biodegradable polymers as biomaterials, Prog. Polym. Sci. 2007, 32, 762.
86. H. R. Allcock, H. Allcock, Chemistry and applications of polyphosphazenes. Wiley-Interscience, Hoboken, 2003.
87. P. Potin, R. De Jaeger,Polyphosphazenes: Synthesis, structures, properties, applications, Eur. Polym. J. 1991, 27, 341.
88. Allcock HR. Chemistry and applications of polyphosphazenes. New York: Wiley; 2003.
89. L. Averous, E. Pollet, Environmental Silicate Nano-Biocomposites. Springer, London Heidelberg New York Dordrecht, pp. 13.
90. M. Ashiuchi, H. Misono,Poly-γ-glutamic Acid, Biopolymers Online 2005, DOI: 10.1002/ 3527600035.bpol7006.
91. R. chandra, renu rustgi;Biodegradable polymers; Prog. Polym. Sci., Vol. 23, 1274
92. Vasanthi K; Biodegradable Polymers - A Review; iMedPub Journals;2017;3;3
93. Shah, A.A.; Hasan, F.; Hameed, A.; Ahmed, S. Biological Degradation of Plastics: A Comprehensive Review. Biotechnol. Adv. 2008,26, 246–265
94. Laycock, B.; Nikoli ́c, M.; Colwell, J.M.; Gauthier, E.; Halley, P.; Bottle, S.; George, G. Lifetime Prediction of Biodegradable Polymers. Prog. Polym. Sci. 2017, 71, 144–189
95. Lucas, N.; Bienaime, C.; Belloy, C.; Queneudec, M.; Silvestre, F.; Nava-Saucedo, J.-E. Polymer Biodegradation: Mechanisms and Estimation Techniques—A Review. Chemosphere 2008, 73, 429–442
96. Sintim, H.Y.; Bary, A.I.; Hayes, D.G.; Wadsworth, L.C.; Anunciado, M.B.; English, M.E.; Bandopadhyay, S.; Schaeffer, S.M.;DeBruyn, J.M.; Miles, C.A.; et al. In Situ Degradation of Biodegradable Plastic Mulch Films in Compost and Agricultural Soils.Sci. Total Environ. 2020, 727
97. Singh, B.; Sharma, N. Mechanistic Implications of Plastic Degradation. Polym. Degrad. Stab. 2008, 93, 561–584
98. Badia, J.D.; Gil-Castell, O.; Ribes-Greus, A. Long-Term Properties and End-of-Life of Polymers from Renewable Resources. Polym.Degrad. Stab. 2017, 137, 35–57
99. Nishida, H. Thermal Degradation. In Poly(Lactic Acid); Auras, R., Lim, L.-T., Selke, S.E.M., Tsuji, H., Eds.; John Wiley & Sons, Inc.: Hoboken, NJ, USA, 2010; pp. 401–412
100. Rabek, J.F. Photodegradation of Polymers; Springer: Berlin/Heidelberg, Germany, 1996; ISBN 978-3-642-80092-4.
101. Kyrikou, I.; Briassoulis, D, Biodegradation of Agricultural Plastic Films: A Critical Review, J polymer.Environ, 2007, 125-150
102. Yousif, E.; Haddad, R. Photodegradation and Photostabilization of Polymers, Especially Polystyrene: Review. Springerplus 2013, 2, 398.
103. Pradeep. J. Patil, Jemmy I. Disouza, Umesh B. Deshannavar; Polymer Biodegradation Basics andApproachestoImprove Biodegradability of Polymer: AReview; IJEDR ,2020;180.
104. Devi, R.; Kannan, V.; Natarajan, K.; Nivas, D.; Kannan, K.; Chandru, S.; Antony, A. The Role of Microbes in Plastic Degradation. In Environmental Waste Management; Chandra, R., Ed.; CRC Press: Boca Raton, FL, USA, 2016; pp. 355–384.
105. Chandra RU, Rustgi R (1998) Biodegradable polymers. Progress in polymer science 23: 1273-1335.
106. Huang SJ, Bitritto M, Leong KW, Pavlisko J, Roby M (1978) JR Knox In: DL Allara and WL Hawkins (eds.) Adv Chem Ser 169: 205.
107. 2 Huang SJ, Bryne C, Palisko JA (1980) ACS Symp Ser 121: 299.173.
108. Albertsson AC (1985) Preprints of the Int Symp on Characterization and Analysis of Polymers 477.
109. Albertsson AC, Anderson SO, Karlsson, S (1987) Polym Degrad Stab 18: 73.
110. Szcz ˛ech, M.; Szczepanowicz, K. Polymeric Core-Shell Nanoparticles Prepared by Spontaneous Emulsification Solvent Evaporation and Functionalized by the Layer-by-Layer Method. Nanomaterials 2020, 10, 496.
111. Traeger, A.; Voelker, S.; Shkodra-Pula, B.; Kretzer, C.; Schubert, S.; Gottschaldt, M.; Schubert, U.S.; Werz, O. Improved bioactivity of the natural product 5-lipoxygenase inhibitor hyperforin by encapsulation into polymeric nanoparticles. Mol. Pharm. 2020, 17, 810–816.
112. Torres-Flores, G.; Nazende, G.T.; Emre, T.A. Preparation of fenofibrate loaded eudragit l100 nanoparticles by nanoprecipitation method. Mater. Today Proc. 2019, 13, 428–435.
113. Günday, C.; Anand, S.; Gencer, H.B.; Munafò, S.; Moroni, L.; Fusco, A.; Donnarumma, G.; Ricci, C.; Hatir, P.C.; Türeli, N.G. Ciprofloxacin-loaded polymeric nanoparticles incorporated electrospun fibers for drug delivery in tissue engineering applications. Drug Deliv. Transl. Res. 2020, 10, 706–720.
114. Bechnak, L.; Khalil, C.; El Kurdi, R.; Khnayzer, R.S.; Patra, D. Curcumin encapsulated colloidal amphiphilic block co-polymeric nanocapsules: Colloidal nanocapsules enhance photodynamic and anticancer activities of curcumin. Photochem. Photobiol. Sci. 2020.
115. Moncalvo, F.; Martinez Espinoza, M.I.; Cellesi, F. Nanosized delivery systems for therapeutic proteins: Clinically validated technologies and advanced development strategies. Front. Bioeng. Biotechnol. 2020, 8, 89.
116. Avramovi´c, N.; Mandi´c, B.; Savi´c-Radojevi´c, A.; Simi´c, T. Polymeric Nanocarriers of Drug Delivery Systems in Cancer Therapy. Pharmaceutics 2020, 12, 298.
117. Lammari, N.; Louaer, O.; Meniai, A.H.; Elaissari, A. Encapsulation of Essential Oils via Nanoprecipitation Process: Overview, Progress, Challenges and Prospects. Pharmaceutics 2020, 12, 431
118. L. Mu, S.S.Feng, A novel controlled release formulation for the anticancer drug paclitaxel (Taxol):
PLGA nanoparticles containing vitamin E TPGS, J. Control. Release 86 (1) (2003) 33–48.
119. C.Fonseca, S.Simoes, R. Gaspar, Paclitaxel-loaded PLGA nanoparticles: prepa-ration, physicochemical characterization and in vitro anti-tumoral activity. I. Control. Release 83 (2) (2002) 273-286
120. F. Danhier, et al., Paclitaxel-loaded PEGylated PLGA-based nanoparticles: in vitro and in vivo evaluation, J. Control. Release 133 (1) (2009) 11–17.
121. D.K. Sahana, et al., PLGA nanoparticles for oral delivery of hydrophobic drugs: influence of organic solvent on nanoparticle formation and release behavior in vitro and in vivo using estradiol as a model drug, J. Pharm. Sci. 97 (4) (2008) 1530–1542.
122. K. Derakhshandeh, M. Erfan, S. Dadashzadeh, Encapsulation of 9- nitrocamptothecin, a novel anticancer drug, in biodegradable nanoparticles: factorial design, characterization and release kinetics, Eur. J. Pharm. Biopharm. 66 (1) (2007) 34–41.
123. M. Teixeira, et al., Development and characterization of PLGA nanospheres and nanocapsules containing xanthone and 3-methoxyxanthone, Eur. J. Pharm. Biopharm. 59 (3) (2005) 491–500
124. F. Esmaeili, et al., Folate-receptor-targeted delivery of docetaxel nanoparticles prepared by PLGA–PEG–folate conjugate, J. Drug Target 16 (5) (2008) 415–423.
125. Y. Yin, et al., Lectin-conjugated PLGA nanoparticles loaded with thymopentin: ex vivo bioadhesion and in vivo biodistribution, J. Control. Release 123 (1) (2007) 27–38.
126. C Gomez-Gaete, et al., Encapsulation of dexamethasone into biodegradable polymeric nanoparticles, Int. J. Pharm. 331 (2) (2007) 153–159.
127. Escalona-Rayo, O.; Fuentes-Vázquez, P.; Jardon-Xicotencatl, S.; García-Tovar, C.G.; Mendoza-Elvira, S.; Quintanar-Guerrero, D. Rapamycin-loaded polysorbate 80-coated PLGA nanoparticles: Optimization of formulation variables and in vitro anti-glioma assessment. J. Drug Deliv. Sci. Technol. 2019, 52, 488–499.
128. Qiu, F.; Meng, T.; Chen, Q.; Zhou, K.; Shao, Y.; Matlock, G.; Ma, X.; Wu, W.; Du, Y.; Wang, X. Fenofibrate-loaded biodegradable nanoparticles for the treatment of experimental diabetic retinopathy and neovascular age-related macular degeneration. Mol. Pharm. 2019, 16, 1958–1970
129. Gao, M.; Long, X.; Du, J.; Teng, M.; Zhang, W.; Wang, Y.; Wang, X.; Wang, Z.; Zhang, P.; Li, J. Enhanced curcumin solubility and antibacterial activity by encapsulation in PLGA oily core nanocapsules. Food Funct. 2020, 11, 448–455.
130. Dourado, D. Pharmaceutical Nanotechnology: A Therapeutic Revolution. Int. J. Pharm. Sci. Dev. Res. 2020, 6, 009–011.
131. A. Budhian, S.J. Siegel, K.I. Winey, Production of haloperidol-loaded PLGA nanoparticles for extended controlled drug release of haloperidol, J. Microen capsul. 22 (7) (2005) 773–785.
132. Y. Sheng, et al., In vitro macrophage uptake and in vivo biodistribution of PLA-PEG nanoparticles loaded with hemoglobin as blood substitutes: effect of PEG content, J. Mater. Sci. Mater. Med. 20 (9) (2009) 1881–1891.
133. C. Gomez-Gaete, et al., Dexamethasone acetate encapsulation into Trojan particles, J. Control. Release 128 (1) (2008) 41–49.
134. K. Sonaje, et al., Development of biodegradable nanoparticles for oral deliv ery of ellagic acid and evaluation of their antioxidant ef cacy against cyclosporineA-induced nephron toxicity inrats, Pharm.Res.24(5) (2007)899 -908.
135. M.F. Zambaux, et al., Preparation and characterization of protein C-loaded PLA nanoparticles, J. Control. Release 60 (2–3) (1999) 179–188.
136. R.M. Mainardes, et al., Zidovudine-loaded PLA and PLA-PEG blend nanoparti cles: in uence of polymer type on phagocytic uptake by polymorphonuclear cells, J. Pharm. Sci. 98 (1) (2009) 257–267.
137. J. Xing, D. Zhang, T. Tan, Studies on the oridonin-loaded poly (d,l-lactic acid) nanoparticlesinvitroandinvivo,Int.J.Biol.Macromol.40(2)(2007)153–158.
138. Q. Cheng, et al., Brain transport of neurotoxin-I with PLA nanoparticles through intranasal administration in rats: a microdialysis study, Biopharm. Drug Disposition 29 (2008) 431.
139. L. Jean-Christophe, et al., Biodegradable nanoparticles—from sustained release formulations to improved site specific drug delivery, J.Control. Release 39 (1996) 339.
140. J. Matsumoto, et al., Preparation of nanoparticles consisted of poly (l lactide)–poly (ethylene glycol)–poly(l-lactide) and their evaluation in vitro, Int. J. Pharm. 185 (1) (1999) 93–101.
141. D.B. Shenoy, M.M. Amiji, Poly (ethylene oxide)-modi ed poly (epsilon caprolactone) nanoparticles for targeted delivery of tamoxifen in breast cancer, Int. J. Pharm. 293 (1–2) (2005) 261–270.
142. C. Changyong, S.Y. Chae, N. Jae-Won, Thermosensitive poly (N isopropylacrylamide)-b-poly(-caprolactone) nanoparticles for efficient drug delivery system, Polymer 47 (2006) 4571.
143. L.K. Shah, M.M. Amiji, Intracellular delivery of saquinavir in biodegradable polymeric nanoparticles for HIV/AIDS, Pharm. Res. 23 (11) (2006) 2638-2645.
144. S.Y. Kim, Y.M. Lee, Taxol-loaded block copolymer nanospheres composed of methoxy poly (ethylene glycol) and poly(epsilon-caprolactone) as novel anticancer drug carriers, Biomaterials 22 (13) (2001) 1697–1704.
145. D. Zheng, et al., Study on docetaxel-loaded nanoparticles with high antitumor efficacy against malignant melanoma, Acta Biochim. Biophys. Sin. (Shanghai) 41 (7) (2009) 578–587.
146. P. Prabu, A.A.C.N. Dharmaraj, M.S. Khil, S.Y. Park, H.Y. Kim, Preparation, char acterization, in-vitro drug release and cellular uptake of poly(caprolactone) grafted dextran copolymeric nanoparticles loaded with anticancer drug, J. Biomed. Mater. Res. 90A (2008) 1128.
147. Saqib, M.; Ali Bhatti, A.S.; Ahmad, N.M.; Ahmed, N.; Shahnaz, G.; Lebaz, N.; Elaissari, A. Amphotericin B Loaded Polymeric Nanoparticles for Treatment of Leishmania Infections. Nanomaterials 2020, 10, 1152.
148. Z. Lu, et al., Paclitaxel-loaded gelatin nanoparticles for intravesical bladder cancer therapy, Clin. Cancer Res. 10 (2004) 7677.
149. A. Kaur, S. Jain, A.K. Tiwary, Mannan-coated gelatin nanoparticles for sus tained and targeted delivery of didanosine: in vitro and in vivo evaluation, Acta Pharm. 58 (1) (2008) 61–74.
150. A.K. Bajpai, J. Choubey, Design of gelatin nanoparticles as swelling controlled delivery system for chloroquine phosphate, J. Mater. Sci. Mater. Med. 17 (4) (2006) 345–358.
151. B. Sarmento, et al., Alginate/chitosan nanoparticles are effective for oral insulin delivery, Pharm. Res. 24 (12) (2007) 2198–2206.
152. A.M. De Campos, A. Sanchez, M.J. Alonso, Chitosan nanoparticles: a new vehicle for the improvement of the delivery of drugs to the ocular sur face. Application to cyclosporin A, Int. J. Pharm. 224 (1–2) (2001) 159-168.
153. Y.W, et al., Chitosan nanoparticles as a novel delivery system for ammonium glycyrrhizinate, Int. J. Pharm. 295 (1–2) (2005) 235–245
154. Arrieta M P, López J, Preparation and degradation mechanisms of biodegradable poly-mer:, Eur. Polym. J.2014,70-255
155. Zeng, S H, Preparation and degradation mechanisms of biodegradable polymer:, IOP Conf. Ser.: Mater. Sci. Eng. 137 012003,2016,425-26
156. Nakamura, T., Hitomi, S., Shimamoto, T., Hyon, S. H., Watanabe, S. and Shimizu, Y, BIODEGRADABLEPOLYMERS, Biomaterials and Clinical Applications, ed. A. Pizzoferrato, P. G. Machetti, A. Ravaglioli andA. J. C. Lee. Elsevier Science, Amsterdam,1987,759
157. Niu, S., Kurumatani, H., Satoh, S, BIODEGRADABLEPOLYMERS, Watanabe, K., ASAIO Trans.,1993,750-753
158. Małgorzata Geszke- Moritz, “Biodegradable Polymeric Nanoparticle-Based Drug
Delivery Systems: Comprehensive Overview, Perspectives and Challenges,” Polymers
2024, 16, 2536, p. 17, 2024.
Author Information
Authors: Vibha Saxena¹,³*, Adarsh Kamble¹, Rushikesh Kejkar¹, Prathamesh Salunkhe¹, Sana Bagwan¹,
Rupesh Saknure¹, Hemant Swami³
1 Department of Pharmaceutics, Marathwada Mitra Mandal’s College of Pharmacy, Pune 411033
2 Department of Pharmaceutics, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research,
Pimpri, Pune, Maharashtra, India
3Institute of Pharmaceutical Sciences, SAGE University, Indore, Madhya Pradesh, India
Corresponding Author:
Vibha Saxena
Address: Department of Pharmaceutics,
Marathwada Mitra Mandal’s College of Pharmacy,
Pune 411033, Maharashtra, India
Email: vibhas08@gmail.com
Contact No: 7428086433
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