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Technical Review Article | Open Access | Published 2 July 2026
Sphingosomes: A Novel Vesicular Drug Delivery System
Maimuna Fatima¹*, CV Sai Sravani¹, Dr. K. Latha*¹, M.Sujatha¹ | EJPPS | 312 (2026) https://doi.org/10.37521/ejpps31207
Abstract
This novel drug delivery system strives to sustain drug effect at a pre-determined rate or keep up a relatively constant and effective drug amount within the body, along with concomitant reduction in undesirable side effects. Vesicular systems consist of highly ordered assemblies of one or several concentric lipid-bilayers. By enclosing an active medication inside the vesicular structures such as niosomes, liposomes, ethosomes, and pharmacosomes, a transferosomes enhanced therapeutic index can be acquired for both new and existing drug molecules.
Sphingosomes are one such system in which aqueous volume is thoroughly bound to a sphingolipid-bilayer membrane. Sphingosomes resolve the vital downsides of vesicle systems (niosomes, liposomes) such as low stability, poor tumour stocking potency in cancer treatment and less in-vivo circulation time. The present overview indicates that this vesicular system represents a propitious system of drug delivery to supply curative compounds for a vast span of feasible applications.
Keywords: Sphingosomes, Cholesterol, Vesicular systems, Sphingolipids, Lipid-bilayers, Niosomes, Liposomes.
Introduction
Novel drug delivery practice is a definite, most suitable and approachable aspect of developing a delivery system. This system must deliver the therapeutics at a scale required by the body during the course of therapy. The entity must reach the location of action. Most common dosage forms do not fulfil these needs, so presently a vesicular delivery system is a possible course of action to provide the drugs for an intensified effect. Vesicular systems consist of several circular lipid bilayers that form when amphiphilic molecules interact with water. These vesicular systems have been developed with different uses in the disciplines of cosmetics, food industries and pharmaceutics. The drug by way of this delivery approach is transported directly to the infection site, giving rise to fewer or no unfavourable effects with lowered toxicity. The lipid vesicular system has better absorption plus bioavailability for drugs having poor aqueous solubility. Various cardiovascular agents, antidiabetic drugs, NSAIDS, proteins and drugs employed in therapy of glaucoma included in these vesicles have shown refined bioavailability & action in humans.
Vesicular drug delivery is classified further into two types based on its composition:
Lipoidal biocarriers.
Non-lipoidal biocarriers.
Fig.1 gives various examples of lipoidal and non-lipoidal Biocarriers¹.
SPHINGOSOMES
Liposomes have definite issues linked to their stability in conjunction with hydrolysis, oxidation, leaching, degradation, drug aggregation, sedimentation, etc. For that reason, to enhance stability, research has given rise to the occurrence of Sphingosomes. Sphingosomes are concentric, bilayer vesicles comprising an enclosed aqueous core within a membranous lipid bilayer, mainly constituting natural or fabricated sphingolipids. (Fig. 2)
Sphingosomes are a key targeted lipid vesicular drug delivery system. They show improved drug retention properties and also overcome the drawbacks of liposomes and niosomes by exhibiting high stability towards acid hydrolysis ².)
Sphingosomes have substantial stability compared to phospholipid liposomes due to the following reasons:
1. Sphingolipids comprise only amide and ether linkages. They are more highly impervious to hydrolysis than the ester linkage of lecithin.
2. Moreover, they carry fewer double bonds than lecithin, hence are less exposed to rancidity.
3. Further, they absorb a lower amount of oil than lecithin, which consequently changes diameter and geometry ³.
ADVANTAGES
Sphingosomes display various advantages, as described below ³,⁴,⁵.
1. Impart passive targeting selective to malignant tissue.
2. Enhance therapeutic index and effectiveness.
3. Amplify stability through encapsulation.
4. Limiting harmful effects of enclosed agent.
5. Enhance PK effect.
6. The pliability to match with site-specific ligands to attain active targeting.
DISADVANTAGES
The following are the disadvantages of Sphingosomes ³,⁶.
1. Overpriced sphingolipid inhibits the development and utilization of this vesicular system.
2. Poor entrapment efficacy.
CLASSIFICATION OF SPHINGOSOMES
Sphingosomes are classed depending on their structural parameters, including ³,⁷.
➣ Number of bilayers formed.
➣ Width of vesicles resulting.
They are either unilamellar or multilamellar and commonly have an average diameter of 0.05-0.45µ, with the most preferable diameter range being 0.05- 0.2µ ⁸.
1. Small unilamellar vesicles (SUV): comprise a single lipid bilayer and have a diameter within the 10-100nm size range.
2. Large unilamellar vesicles (LUV): made of a single lipid bilayer, having a considerable diameter than SUV and a size range of 100nm-1µm.
3. Multilamellar vesicles (MLV): contain many lipid bilayers having a size range of 100nm-20µm.
4. Oligolamellar vesicles (OLV): possessing more than one bilayer, however, not as many as MLVs. Size range 0.1-1µ.
5. Multivesicular vesicles (MVV): Size range 100nm-20µm.
6. Vesicles above one micrometre (µm) diameter are called Giant vesicles (GV).
FRAMEWORK OF SPHINGOSOMES
Sphingosomes are fabricated using sphingolipids and cholesterol. Sphingolipids along with cholesterol occur in the proportion of 75:25 to 30:50. The most desirable ratio is 55:45 ¹,⁹,¹⁰.
In contrast to other formulations, sphingomyelin and cholesterol-containing liposomal formulations lead to several applications ³.
SPHINGOLIPID
Sphingolipid is so-called as a cell component. Its name was given by J.L.W.Thudichum in 1884, owing to its enigmatic nature. Sphingolipid contains a polar head that attaches to a hydrophobic body. A structure with the composition of sphingolipids (polar lipids) is comparable to human skin lipid, especially in the epidermis layer. Sphingolipid of natural origin includes mammal’s milk (ideally bovine milk), brain, erythrocytes from animal blood (ideally sheep) and egg yolk ¹¹.
Sphingolipids are either synthetic or semi-synthetic. The elementary sphingolipids include ceramide and sphingosine which are scaffolds and complex sphingolipids such as sphingomyelin (SM) and glycosphingolipid. Divergent groups of sphingolipids can be employed in sphingosomes¹².
STRUCTURE OF SPHINGOLIPID
Sphingolipids are a complex family of lipids that share standard structural features. Sphingosine (sphingoid base backbone) is synthesized de novo using serine and a long-chain fatty Acyl CoA and then transformed into phosphosphingolipids, ceramides, glycosphingolipids and various other species ¹¹.
The sphingosine backbone is O-linked to the charged head groups such as serine, ethanolamine or choline. The backbone is likewise amide-linked to an acyl group, such as a fatty acid ¹¹.
Fig.3 depicts the general chemical structure of Sphingolipid.
CLASSIFICATION OF SPHINGOLIPIDS
Sphingolipids are classified into three types which vary based on substituents on their head group:
➣ Ceramides
➣ Sphingomyelins
➣ Glycosphingolipids
Fig.4 gives a broad classification for sphingolipids ¹³,¹⁴.
CHOLESTEROL
A sphingosome bilayer containing sterol brings about crucial modifications in formation of membrane. Cholesterol alone does not form a bilayer structure, rather is incorporated into sphingolipid layers in very high concentrations up to 1:1 or 2:1 molar ratio of cholesterol to sphingolipid. Cholesterol addition increases the partition mediating choline head group and eliminates normal hydrogen bonding interaction and electrostatic interactions ³,⁸.
Sphingosome stability can be intensified by the inclusion of stearyl amine (SA), a positive charge-inducing agent for the insertion of secondary constituent’s target sphingosomes into particular cell types. For instance, the binding of sphingosomes to the epitopes on certain cell types is accomplished when sphingosomes are associated with monoclonal antibodies/binding fragments, such as cancer-associated antigens, which provide a means to target the sphingosomes after systemic administration ³,¹².
INTERACTIVITY BETWEEN SPHINGOLIPIDS AND CHOLESTEROL
Cholesterol preferentially interacts with sphingolipid over phosphatidylcholine which comprises an acyl chain. A positive association exists between concentration of cholesterol and sphingolipids in varied membrane fractions. Cholesterol desorption, in monolayer membranes, along with bilayer systems, has shown that cholesterol desorbs much slowly from sphingomyelin-rich membranes, or is confined more keenly in sphingomyelin-containing acceptor vesicles than in case of acyl-chain containing phosphatidylcholines. These interactions also have a positive application for sphingosome in achieving better biological effectiveness ².
SPHINGOSOMES PREPARATION TECHNIQUES
1. Lipid Film Formation (Handshaking method):
Sphingolipids, surfactant/cholesterol and lipophilic drug are mixed and dissolved in an organic solvent taken in an RBF. Organic solvent is drawn out using a rotary film evaporator with reduced pressure. Hydration of dried film with aqueous phase around 50-60°C is carried out. Hydration results in the dry lipid layer inflating and parting from the inner side of RBF and forming multilamellar sphingosomal vesicles ¹⁵,¹⁶.
2. Solvent Spherule Method:
In the solvent spherules method, the sphingolipids are liquefied in a volatile hydrophilic solvent which is dispersed into solution. Then volatile hydrophilic organic solvent is evaporated using a water bath under controlled conditions. Thereby, MLVs are fabricated ¹⁷,¹⁸.
3. Calcium-Induced fusion technique:
In calcium-induced fusion, the MLVs are formed when added calcium is combined with SUV sphingosomes. On the introduction of EDTA, large unilamellar vesicle sphingosomes can be created from multilamellar sphingosome vesicles. This technique is used for encapsulating macromolecules ¹⁹.
4. French-pressure cell method:
A useful method for fabricating more stable unilamellar or oligolamellar sphingosomes in contrast to sonicated vesicles. This technique is accomplished under extreme high pressure by making use of a French press ²⁰.
TRANSPORT PROCESS OF SPHINGOSOMES
For cellular level transportation, numerous procedures directing small unilamellar sphingosomal vesicles (SUSV’s) to interact with a cell are available, for instance Stable adsorption, Endocytosis, Fusion and Lipid transfer ²¹.
➣ Stable adsorption:
Adsorption is a method of association of cell surface with intact vesicles. Such a process is facilitated by hydrophobic, non-specific electrostatic or other forces/components present in the vesicles or at cell surface ¹,².
➣ Endocytosis:
This is an action of delivering the intact vesicle taken up by the endocytic vesicles to lysosomal tools ¹,²,³.
➣ Fusion:
The vesicular bilayer simply joins with the plasma membrane then releases the vesicular content into the cytoplasmic space ¹,².
➣ Lipid Transfer:
Transfer of respective lipid molecule between vesicles and cell surface without any cell association of the aqueous vesicle content ¹,²,³.
CHARACTERIZATION OF SPHINGOSOMES
1. Vesicular characterization- utilized for measuring important vesicular characters such as particle size, shape and also zeta potential ¹,⁸.
2. Transition temperature- For evaluating transition temperature of bilayer vesicles; for this purpose, DSC (Differential scanning Calorimetry) is used ¹.
3. Penetration study- The method mainly employed for penetration study is confocal laser scanning microscopy (CLSM) ¹.
4. Vesicle stability- The vesicular stability is influenced by parameters such as structure and shape. It is feasible to view structural and shape changes using transmission electron microscopy (TEM) ¹.
5. Entrapment efficiency- The ultracentrifugation technique is utilized for measuring entrapment efficiency ¹.
6. Sphingolipid cholesterol interaction– DSC (Differential scanning Calorimetry) and 31P NMR are employed ¹.
7. Permeation study- Permeation study is carried by incorporating sphingosomes with gel. Franz diffusion is employed in diffusion studies ¹,⁸.
8. Drug content- Drug amount is estimated by making use of Ultraviolet spectrophotometry and High-performance liquid chromatography (HPLC) ¹.
THERAPEUTIC RELEVANCE OF SPHINGOSOMES
Sphingosomes are efficient carriers for drug targeting to the site of action, because of it being innocuous in nature, biodegradable and identical to biological membranes. The following are some of the applications of sphingosomes ¹¹.
1. Sphingosomes are utilised for antifungal, antimicrobial and antiviral (anti-HIV) therapy ⁷,²².
Examples: Ciprofloxacin, Vancomycin, Amoxicillin, Amphotericin.
2. Sphingosomes in cosmetics ⁷.
3. Sphingosomes as drug delivery vehicles ²²,²³.
4. Sphingosomes for tumour therapy ²³.
5. Sphingosomes for gene therapy ⁷.
6. Sphingosomes can be employed for ocular DDS ²¹.
7. Sphingosomes can be bought into use for gene delivery ²¹.
8. Sphingosomes maybe employed for enzyme immobilization ⁷,²¹.
Conclusion
Sphingosomes are bilayer vesicles retaining an aqueous core enclosed by membrane lipid bilayers which are form by natural/fabricated sphingolipids. Having high stability, targeting specific organs and tissues, high drug stocking range, being well-matched and safer to host cells these are appraised as novel vesicular drug delivery systems. They have great potential in designing novel vesicular systems and can be widely employed in a vast range of fields. Thus, they are trusted as safe delivery systems.
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Author Information
Authors: Maimuna Fatima¹*, CV Sai Sravani¹, Dr. K. Latha*¹, M.Sujatha¹
Corresponding Author: Dr. K. Latha M.Pharm, Ph.D. Professor
Address: Dept. of Pharmaceutics
G.Pulla Reddy College of Pharmacy,
Mehdipatnam, Hyderabad-28
Contact No.: 9848630966
E-mail ID: k.latha@gprcp.ac.in
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