- lauraclark849
- Oct 8
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Technical Review Article | Open Access | Published 8th October 2025
Current Developments In Microfluidic Platforms For Controlled Drug Delivery
Aditya Pratap Singh, Akanksha Dwivedi* , G.N. Darwhekar Acropolis Institute of Pharmaceutical Education and Research, Indore-453771, Madhya Pradesh,. | EJPPS | 303 (2025) https://doi.org/10.37521/ejpps30303
Abstract
The quest for precision medicine, individualization and minimal invasiveness, have prompted a change from traditional delivery methods to more intelligent, regulated techniques that improve therapeutic results and reduce adverse effects. In this transition, microfluidic platforms-which can manipulate fluids at the microscale-have become a game-changing answer. Recent developments in lab-on-a-chip (LOC) systems, microneedle-assisted platforms, and drug-carrier-integrated devices are highlighted in this review on microfluidics-enabled drug delivery. Along with important material issues like biocompatibility, chemical resistance and mechanical qualities, this review describes important microfabrication processes including photolithography, soft lithography, and 3D printing. Microfluidic systems have found use in diagnostics, nanomedicine, organ-on-chip models, and paediatric-friendly technologies because of their adaptability. These technologies enable high-throughput, portable and affordable options for point-of-care and customized medicines in addition to providing temporal and geographic control over drug release. Microfluidic-controlled medication delivery has the potential to revolutionize treatment approaches for complicated illnesses in the near future by bridging the gap between engineering and biomedicine.
Keywords: Microfluidic, Microneedle-platform, controlled drug delivery, Lab-on-a-chip (LOC), biocompatible materials.
Overview
Systems for delivering therapeutic chemicals to biological systems have proven essential in guaranteeing that the medications or substances delivered have the intended therapeutic efficacy with the fewest possible adverse effects. Numerous methods, such as transdermal administration, oral administration, inhalation, and hypodermic injections, can be used to deliver drugs¹. By delivering medications to the intended locations, releasing them instantly, extending their release, or creating a pulsating discharge that is based on the illnesses and the drugs' modes of action, drug delivery systems guarantee the therapeutic drugs' maximal efficacy.
Despite being the most widely used delivery methods, conventional means of drug delivery have several disadvantages. The challenge of attaining selective distribution to tissues and cells is among the main disadvantages of traditional medication administration. This is because drugs are uniformly dispersed throughout the body prior to arriving at pathological areas of action and may deteriorate or become inactive during passage through various biological boundaries². Approximately 80% of medications are taken orally. There are restrictions on the absorption and metabolism of oral medications. Other restrictions related to oral delivery include enzymatic breakdown, degradation brought on by a shift in the body's pH, adverse effects, variable transit durations, and first-pass metabolism³. The lengthy needles used in hypodermic injections penetrate the nerve endings, causing discomfort.
Initially, oral and transdermal sustained release devices were developed in the early 1950s, controlled drug delivery systems progressed to systems for self-regulated medication delivery, delivery systems based on micro and nanotechnology, and zero-order release systems⁴. As a result of the field's expansion, various innovative drug delivery technologies have been created, such as Nanoparticles (NPs), antibody-drug conjugates, microneedles (MNs), and transdermal patches, micro-reservoir implants, and more⁵. Therapeutic medications including peptides, vaccines, enzymes, and others can be administered more effectively and have better pharmacokinetics with the use of systems for the controlled distribution of drugs. By boosting absorption, stopping premature deterioration, preserving drugs within the window of therapeutic use, and focussing on particular tissues or cells, they boost the bioavailability of therapeutic pharmaceuticals and lessen side effects.
Microtechnology for regulated medication administration
The rapidly expanding discipline of Laboratory-on-a-chip (LOC) for microfluidic delivery involves working with extremely small volumes of fluids inside a device that contains micro-level features. To analyse complicated biological fluids or administer therapeutic substances, microfluidic devices made using microfabrication techniques combine several parts and functions, into a small instrument for testing, synthesis, and sampling. It is possible to automate these devices⁶. They also boast several other noteworthy qualities, such as high throughput, low cost, portability, and well-controlled microenvironments. Within a miniature microfluidic device, processes can be effectively and accurately regulated. Using microtechnology to administer drugs in a regulated manner includes creating and assembling different parts for mechanisms for delivering drugs, implanting the devices in the bodies of humans or animals, creating therapeutic channels or carriers, and delivering the medications to the appropriate cells or tissues.
Drugs can be delivered using LOC-based devices at a steady pace, improving therapeutic efficacy and avoiding the negative effects of burst release in traditional approaches. As they move via the long path in a traditional medication delivery method, proteins, peptides, or DNA-based medications may become ineffective because of enzymatic breakdown⁷. Microfluidic technologies have recently advanced to help minimise the delivery channel and make it possible for controlled and precise drug distribution, for instance by implanted microdevices.
This article examines current developments in microfluidic systems for regulated medication transportation. There are three primary types of microfluidic controlled drug delivery platforms: MNs-based drug delivery systems, drug carrier-integrated microfluidic LOC systems, and drug carrier-free microfluidic. It begins with a quick overview of microfabrication methods and medication delivery systems.
Microfabrication techniques
Photolithography, etching, micromachining, micromilling, depositing, mould assembly, reproduction, and laser ablation are some of the methods now used to create these microsystems. Microsystems are generally made using four main processes: bonding, etching, deposition, and patterning⁸⁻¹¹. Patterning is a basic method used in microfabrication techniques, specifically to move the intended designs of every element, such as on a silicon, glass, metal, and polymer-based chip substrate, microchannels¹². Patterning has been accomplished by the use of photolithography and soft lithography, which involve applying a photomask design on a layer of photoresist while exposed to UV light.¹³,¹⁴,¹⁵
Most structures are visible following the successive etching procedures. Furthermore, a closed system must be formed in many circumstances. Thus, a variety of bonding techniques, including thermal bonding, anodic bonding, and photopolymer adhesives, are needed to reversibly or irreversibly link two or more substrates together¹⁶⁻¹⁹. Since this review article is not about microfabrication, these review articles and books provide more in-depth information about microfabrication techniques.
Microfluidic device
Durability, biocompatibility, chemical resistance, and optical qualities are important considerations when choosing materials for microfluidic devices. Paper, silicon, glass, and polymers are examples of common materials. Although silicon is opaque and brittle, it has exceptional thermal and chemical stability. Although glass is thermally durable, biocompatible, and chemically inert, its utility in cell culture applications is limited by its high impermeability and labour-intensive processing.²⁰⁻²². Instead, a lot of research has been done on using polymeric materials to create microfluidic devices. The advantages of polymeric materials over silicon and glass include reduced costs, easier production, greater transparency, and higher heat resistance²³. Polydimethylsiloxane (PDMS), a soft elastomer that is optically transparent (Figure 1c), is a typical material²⁴. PDMS has qualities like excellent elasticity, air permeability, light transmission, biocompatibility, and natural hydrophobicity²⁵,²⁶. It is also reasonably priced and simple to mould. Cell screening, long-term cell culture and biochemical experiments can all benefit from it. High flow rates also cause microchannels to enlarge. Organic solvents that produce microchannel deformation may be absorbed by PDMS.
Recently developed, paper-based microfluidic devices are inexpensive, portable, simple to fabricate, and compatible with other devices. Capillary activity within the cellulose matrix, which is necessary for fluid transport, can be regulated by hydrophobic changes. Furthermore, because of its micro/nanostructure, paper can be used as a 3D scaffold for cell culture, mimicking important microenvironmental conditions.
Replica moulding, another name for soft lithography, is another popular method for fabricating microfluidic chips. PDMS microfluidics devices are traditionally made using design of the photomask, optical exposure, and photoresist spin coating, PDMS replica generation along with creation, and sealing²⁷. One alternative manufacturing technique for creating microfluidic devices is 3D printing, which has gained popularity due to its special qualities²⁸.
Manufacturing Microfluidic Device
Microfluidic Instrument Material
Because microscale characteristics greatly affect performance, choosing the best material is essential in order to manufacture microfluidic devices. Durability, transparency, biocompatibility, chemical compatibility, surface wettability, and ease of production are important considerations²⁹,³⁰. Ceramics, metals, polymers, silicon, and glass are common materials; every one has benefits and drawbacks depending on the use³¹. Metals can be used to fabricate microfluidic devices because they are affordable, strong, and resistant to chemicals, high heat, and pressure. Common options include iron, copper, and aluminium, they are commonly used to increase chemical resistance in alloys. In the actual synthesis of the nanomaterials, metals are especially helpful. Because of its versatility in design, thermostability, and chemical compatibility, silicon finds extensive application in microfluidics. Its fragility makes integrating active components difficult, and its opacity restricts optical detection. For organ-on-a-chip devices and other biological applications and medical diagnostics, silicon is still useful despite its high cost.
Table 1 Evaluation and comparison of various materials for the creation of platforms that are microfluidic ³²,³³,³⁴
Features | Metal | Silicon | Glass | Ceramics | Hydrogel | Paper |
Minimal Price | Positive | Not at all | Negative | Good | Good | Good |
Fabrication Simplicity | Positive | Not at all | Negative | Good | In the middle | Positive |
Excellent Mechanical Prpertities | Good | Good | Good | Negative | In the middle | Good |
Sterilisation ease | Good | Good | Not at all | Not at all | Not at all | |
Young's modulus of flexibility | Not at all (between 100 and 200) | Not at all (between 130 and 180) | Not at all (between50 and 90) | Not at all (between 65 and 250) | Good (minimal) | Positive (between 0.0003 and 0.0025) |
Oxygen permeability (Barrier) | Not at all (<0.01) | Not at all (0.01) | Good (>1) | Good (>1) | Positive (>1) | |
Biocompatibility | Positive | Positive | Moderate | Positive | Positive | |
Clarity of Vision | Not at all | Good | Not at all | Good | Negative | |
Low absorption | Not at all | Good | Good | Good | Moderate | Moderate |
Method of Chip Fabrication
A lot has been accomplished in microfluidics in a very brief period because of numerous developments in technology from other domains that have caught the curiosity of academics and been modified for chip fabrication. Some of the most crucial findings which have helped are advancements in fluid dynamics. As discussed earlier, a gadget using microfluids can be made from an assortment of materials. These materials will all behave differently during processing since they each have distinct properties³⁵,³⁶
There are currently several fabrication techniques that have been defined and used.³⁷⁻³⁹
Table. 2 The grouping of methods for microfluidic manufacturing.
Process | Removal of material technique | Depositing materials technique |
Chemical Process | Electrochemical machining via discharge Wet etching Dry etching | Silicon Surface micromachining Lithography Powered 3D printing |
Mechanical Process | Micro-milling Micro-grinding Ultrasonic machining | Injection moulding Hot embossing |
Laser based processes | Photothermal processes Ultra-short pulse processes Laser direct machining | Selective laser sintering Two-photon polymerization |
3. Controlled medication delivery using microfluidic systems without drug carriers
Drug carriers on a chip or direct drug carrier-free delivery are two methods of controlled drug delivery that have seen an increase in use on microfluidic platforms.⁴⁰ Both fully integrated microfluidic LOC devices and basic micro-reservoir-based devices are the two categories into which drug carrier-free microfluidic systems fall, with implanted devices attracting particular attention.⁴¹⁻⁴⁴
MNs-Based System
MNs are a unique transdermal drug delivery method that have been studied in recent decades. They can address some of the drawbacks of conventional subcutaneous and oral delivery. MNs are readily able to penetrate the skin's Corneum stratum (SC), which acts as a roadblock for medication molecules. Additionally, patients have the ability to use MNs to simply self-medicate. Because of their small size, MNs are capable of adjustment within the range from 10 µm to 1 mm in length. This represents a tiny portion of a subcutaneous injection needle, allowing for painless treatment⁴⁶,⁴⁷,⁴⁸. Delivery of MNs percutaneously can circumvent inadequate absorption brought on through the breakdown of medications via the metabolic system, in contrast to typical oral administration⁴⁹.
Solid MN’s
Solid microneedles (MNs) are composed of materials such as silicone, metallised, and polymers by employing methods such as 3D printing and laser cutting. Their drug delivery system (DDS) follows a two-step process: first, MNs create micro-channels in the skin, then drugs diffuse passively for therapeutic effects. The efficiency is dependent on the length and shape of the MNs. MNs of solid silicon were optimised by Narayanan et al. with a height of 158 µm and high mechanical strength, enhancing percutaneous drug delivery. Li et al. developed biodegradable polylactic acid (PLA) MNs, finding that size, drug concentration, viscosity, and administration time affect efficiency, achieving effective insulin delivery.⁵⁰,⁵¹
Coated MN’s
By directly applying medications and biodegradable materials to their surface, coated micro-needles (MNs) enable regulated drug release upon skin penetration. Medication stability is improved and multimodal medication administration is made possible by this coating technique. For the administration of a multifunctional DNA vaccine, DeMuth et al. created a coating method applied layer by layer. In order to deliver the pH1N1 DNA vaccine intradermally, Hae Yong et al. employed polymer-coated MNs with PLGA/PEI nanoparticles, which demonstrated an enhanced immune response. Andreas et al. suggested a transdermal drug delivery system that uses evaporation-induced droplet transport to guarantee accurate drug dose. The device controls drug deposition by considering variables such as needle exposure time, liquid characteristics, and MN structure.⁵³
Dissolving MN’s
Composed of materials like polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP), which are biodegradable and biocompatible, dissolving microneedles (MNs) provide regulated drug release as they dissolve in the skin. Though they dissolve more slowly and have less mechanical strength than other MN types, they don't leave any residues. In response to these problems, a polylactic acid (PLA) dissolving MN was developed by Cha et al. that has better strength and destruction characteristics. For effective medication administration, Guo and colleagues created a dissolving MN that was packed with a nanostructured lipid carrier (NLC), which effectively decreased inflammation and arrhythmia in animal models. In order to improve photodynamic treatment (PDT) for tumours, Zhao and colleagues developed a sodium hyaluronate (HA) MN that dissolves quickly. After 4 minutes, 75% of the MN dissolved, raising the tumour inhibition rate from 66% (conventional injection) to 97%.⁵⁴,⁵⁵
Micro-reservoir system
One or more drug reservoirs are used in the micro-reservoir system to store and release drugs under regulated conditions. In contrast to conventional drug delivery methods, it allows for a number of dosing schemes, such as pulsatile, on-demand, and zero-order release. By increasing drug stability and extending release time, microfluidic technology improves delivery of drugs precision in-vitro and in-vivo ⁵⁶. One driving mechanism that is an essential part of this system is that it guarantees stable and accurate medication delivery. Active or passive modes of operation are possible for micro-reservoir systems, depending on the actuation technique⁵⁷.
4. Uses for Microfluidic Instruments
There are many uses for microfluidic technologies, which seek to rectify the drawbacks of traditional assays. There is considerable promise for sequencing of DNA, personalised medicines, disease diagnostics, drug delivery, drug screening, cell culture, cell separation, cell treatment, and chemical screening⁵⁸,⁵⁹. Furthermore, there are numerous applications for the particles produced in microreactors, consisting of textiles, electronics, energy, gene delivery, biotechnology, bioimaging, and biosensing⁶⁰.
Diagnosis Device
Rapid and precise diagnosis is made possible by microfluidic devices, which analyse samples such as tissues, blood, and saliva. They are frequently employed in conjunction with analytical techniques for pathogen identification and microbial extraction⁶¹. Microfluidic chips, for instance, can increase bacterial contact with channel walls by creating twisted airflow, which allows them to catch airborne infections. This enables the effective capture of microorganisms in tiny liquid volumes for examination using nucleic acids or the immune system⁶².
Genetic-based disorders can be diagnosed on-chip using DNA analysis, similar to how infections or disease indicators are identified. Microchips that incorporate the Polymerase Chain Reaction (PCR) can accomplish this. The microfluidic platform is capable of serving as a point of care tool for quick and precise PCR analyses using primers and additional chemicals and managing the reaction conditions ⁶³. This situation involves the detection of foetal chromosomal aneuploidy using microfluidic digital PCR.
Cell culture media
By closely simulating real tissue environments and offering controlled biochemical and biophysical cues, microfluidic culture technologies present a possible substitute for conventional cell culture. While eliminating the drawbacks of in vivo research, these systems enable investigations on tissue growth, rejuvenation, and disease⁶⁴. Organs-on-a-chip technology is gaining traction because it can speed up drug discovery, lower expenses, and give a more accurate model of human physiology than animal testing. The integration of several chips with various cell types allows for the simulation of whole-body reactions. The use of biomimetic microfluidic technology to replicate organ-level activities like the kidneys, liver, and lungs is of special interest to researchers⁶⁵.
Since kidney on a chip platforms mimic the environment of renal tubular cells, they have also garnered a lot of interest in the field of microfluidics.
Nanomaterial synthesis platform
Particularly when it comes to targeted medicine delivery, biosensors, diagnostics, and therapies, nanotechnology has revolutionised contemporary medicine. Pharmaceuticals based on nanotechnology are already being used in many clinical settings, and more are being developed. Nanoparticles with consistent size, shape, and great encapsulation efficiency can be synthesised using microfluidic devices⁶⁶. Because of their better brightness and contrast, these nanoparticles improve imaging methods such as ultrasound, magnetic resonance, and fluorescence. For positron emission tomography (PET), a non-invasive diagnostic procedure that uses positron-emitting medications, radioisotopes are also produced in microfluidic reactors⁶⁷,⁶⁸.
By precisely controlling the characteristics of nanoparticles, microfluidic nanosynthesis improves the performance of biosensors⁶⁹. One important substance that responds visibly in response to environmental cues such solvents, pH, temperature, and molecular recognition is polydiacetylene (PDA), which changes colour and fluoresces. Its homogeneous, self-assembling particles optimise its optical and structural characteristics. PDA-based sensors are inexpensive and easy to use, and they are utilised in point-of-care ovarian cancer diagnostics, wearable vapour sensors, smartphone solvent detection, and 3D-printed detoxifying materials.
Microfluidic template sticker
This approach involves creating ‘template stickers’ that can be combined and selected according to each reaction's requirements. Each sticker in the toolbox contains a set of standardized stickers that each represent a different part of the finished product chip that uses microfluids. The microfluidic devices produced by this mobile, low-cost, and time-saving fabrication approach have distinct features, optimal performance, and customizability⁷⁰.
Devices for paediatrics
Microfluidics also presents an option for paediatric patients or patients with diseases that complicate the sample procedure. In the case of cystic fibrosis, for example, the sweat chloride test may be conducted using microfluidic devices⁷¹.
Because the minimal amount of sweat and evaporation limit the possible sample volume, this is useful as just a small volume sample is needed.
Conclusion
With its unmatched precision, efficiency, and customisation, recent developments in microfluidic technologies have drastically changed the field of controlled drug delivery. Through precise fluid manipulation at the microscale made possible by these technologies, consistent drug carriers, on-demand administration, and real-time dose control can be produced while reducing adverse effects and improving therapeutic results. Microfluidic technologies, which combine automation, bioengineering, and materials science, are opening the door for next-generation medication delivery systems that may be customized to meet the needs of specific patients. Microfluidics has the potential to transform clinical practice and pharmaceutical development as long as research on scalability, biocompatibility, and regulatory issues continues.
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Author Information
Authors: Aditya Pratap Singh, Akanksha Dwivedi*, G.N. Darwhekar
Acropolis Institute of Pharmaceutical Education and Research, Indore-453771, Madhya Pradesh, India
Corresponding Author:
Dr. Akanksha Dwivedi, Research Scholar, Department of Pharmaceutical Sciences, PES University
Address: Acropolis Institute of Pharmaceutical Education and Research, Indore-453771, Madhya Pradesh, India
Email: akd.pharma@gmail.com
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