1. INTRODUCTION:

he discovery and development of new drugs continue to be a formidable challenge in pharmaceutical research. Despite significant advances in medicinal chemistry and molecular biology, the attrition rate of drug candidates remains high, with many compounds failing during clinical evaluation due to inadequate efficacy or adverse effects.

Moreover, even approved drugs often exhibit limitations related to poor bioavailability, systemic toxicity, or suboptimal pharmacokinetic profiles. These challenges underscore the importance of innovative drug delivery technologies designed to optimize therapeutic performance and minimize side effects^1-3.

Nanotechnology has emerged as a transformative approach in this regard, offering novel strategies to enhance drug solubility, stability, targeting, and controlled release. Among the diverse nanocarrier systems developed, nanofibers fabricated via electrospinning technology have attracted substantial attention for pharmaceutical applications. Electrospinning is a straightforward and versatile technique that employs a high-voltage electric field to draw polymer solutions or melts into continuous ultrafine fibers with diameters typically ranging from tens of nanometers to a few micrometers.

Since its initial conceptualization in the early 20th century and subsequent technological advancements in the 1990s, electrospinning has evolved into a powerful platform to engineer nanofibrous drug delivery systems. These nanofibers offer unique advantages including high surface area-to-volume ratios, tunable porosity, and the capability to incorporate a wide range of therapeutic agents, enabling controlled and targeted drug release. Consequently, electrospun nanofibers are being extensively explored in areas such as transdermal delivery, wound healing, tissue engineering scaffolds, and oral and implantable drug delivery systems^4,5.

This review aims to provide a comprehensive overview of electrospinning technology, its principles, and its diverse pharmaceutical applications in drug delivery. Emphasis is placed on the design considerations, materials used, and recent advances in fabricating electrospun nanofibers for improved therapeutic outcomes.

2. ELECTROSPINNING PROCESS:

The widely used technique of electrospinning (ES) is renowned for its ease of use, efficiency, and promise for producing drug- or bioactive-loaded nanofibers for use in pharmaceutical applications. A conductive collection unit, a spinneret, and a high voltage power supply unit are the three primary parts of ES. A new technique has emerged in recent years that entails loading a syringe with a viscous polymeric solution, melt, or blend and pushing it through a needle to create nanofibers at the right flow rate and needle diameter. An important consideration in this procedure is the distance between the needle tip and the collection drum^6,7. The Taylor cone, a cone-shaped droplet formed by the polymeric solution when it reaches the needle's tip, changes into a jet when an electric current passes through it. To gain a deeper comprehension, please refer to Figure 1

Figure 1- Process of Electrospinning

In an ideal electric field, polymeric droplets can eject polymeric electrospun nanofibers by overcoming surface tension. After that, these nanofibers are gathered on a drum. Numerous elements, including centrifugal, mechanical, gravitational, and physical forces, are involved in the production of these electrospun nanofibers. The favored option for pharmaceutical and biomedical applications is polymeric solutions due to the intermolecular and intramolecular interactions and the viscosity properties of the electrospinning solution. The flexibility to use a variety of polymer-based processes, convenience of use, and the production of nanofibers with adjustable width, structure, and texture are just a few advantages that electrospinning technology offers for pharmaceutical applications⁸.

3. ELECTROSPINNING TYPES:

In general, the type of ES technique used determines how flexible Nano Fibers (NF) are manufactured¹⁴.Typical forms of electrospinning (ES) include:

(a) Electrospinning blending;

(b) Electrospinning melts;

(d) Blending; and

(e) Co-axial electrospinning

1) Electrospinning blending:

Blend electrospinning is a widely utilized and well-established ES technique. It involves combining bioactive or medicinal compounds with a polymeric ES solution, where they are either dissolved or distributed before being spun into fibers (Figure 2a). This process ensures the uniform dispersion of the drug or bioactive agent within the resulting nanofibers (NFs). However, the use of solvents during the preparation of blends, dispersions, or solutions may lead to bioactive denaturation, potentially causing the molecules (drugs or bioactive agents) to be released prematurely⁹.

2) Co-axial electrospinning:

Co-axial electrospinning addresses the limitations of blend electrospinning. This technique utilizes two nozzles connected to a high voltage source, each dispensing a separate solution-such as natural or synthetic polymers, drugs, or bioactive compounds (Figure 2b)¹⁰. Typically, the polymeric solution is injected into the outer jet (co-spun), while the drug or bioactive substance is introduced into the inner jet. This configuration encapsulates the active ingredient within the nanofiber (NF) core, surrounded by a polymeric shell, enabling a sustained release of the active compound¹¹. As a result, this ES method helps prevent or reduce the denaturation of bioactive proteins¹².

Figure 2: ES Types: a) Electrospinning blending, b) Co-axial Electrospinning, c) Emulsion Electrospinning

3) Emulsion electrospinning:

Blend electrospinning is similar to emulsion electrospinning, as both rely on the composition of two immiscible solvent systems, typically a water/oil emulsion. In the resulting emulsion, the nanofibers (NFs) exhibit a distinct core-shell structure during the spinning process. To put it briefly, the active ingredient and surfactant combine to form the W/O emulsion, which is then combined with appropriate natural or synthetic polymers and spun to create fiber (Figure 2c)¹³. It then transforms into the axial region's droplet enrichment and viscous gradient. Consequently, the resultant NFs provide a sustained release of active and overcome the initial burst release of active¹⁴.

4) Melt electrospinning:

The conventional electrospinning (ES) technique follows the standard ES process. In simple terms, melt electrospinning involves heating a polymer (natural or synthetic), along with a drug and other excipients, until they melt and are subsequently ejected through a capillary (Figure 3a)¹⁵.

5) Gas jet electrospinning:

In general, this type of electrospinning offers a commendable improvement over conventional melt electrospinning. It gets around melt ES's temperature-dependent limitations. The gas jet assembly is connected to the ES configuration (Figure 3b). Here, the NFs close to the nozzle receive enough heat from the hot gas covering the coaxial jet to cause a delay in their solidification¹⁶.

Figure 3: ES Types: a) Melt Electrospinning, b) Gas jet electrospinning

4. ELECTROSPINNING CHARACTERISTIC AND HOW THEY AFFECT ELECTROSPUN FIBER PROPERTIES:¹⁷

(a) Voltage: The diameter first lowers and then increases when the voltage rises above a critical value. Increased repulsion forces are the cause of the initial diameter drop.

(b) Distance Between the Electrode and the Collector: When the distance is too short, there is insufficient time for solvent evaporation, leading to the formation of flattened nanofibers.

(c) Flow rate: As the flow rate increases, the diameter of the Taylor cone initially decreases due to the higher volume of polymer solution within the cone. However, a further increase in flow rate leads to the formation of beads

(d) Surface tension: Proper jet initiation results from lower surface tension.

(e) Conductivity: Solutions with high conductivity can carry more charges, which raises the applied voltage. A higher voltage causes the diameter to drop.

(f) Humidity levels: the pearl effect intensifies as relative humidity rises.

(g)Viscosity: Highly viscous liquids tend to generate droplets as they travel from the needle to the collector, which eventually leads to the formation of beads

(h) Solution concentration: As concentration rises, viscosity rises as well, forming droplets that dry out upon arrival at the collection.

(i) Temperature: A rise in temperature also raises the solution's concentration, which raises viscosity. The beaded morphology is diminished by this higher viscosity.

5. EXCIPIETNS USED IN THE ELECTROSPINNING:

The production of customized nanofibers relies on one or more polymers, solvents, and surfactants. Depending on the type of polymer, changes may be made to mechanical characteristics, stability, solubility, and drug release. Polymeric solutions are produced using a variety of solvent types, including inorganic and organic solvents.

5.1 POLYMERS USED IN THE ELECTROSPINNING:

Nanofibers must meet certain requirements for mechanical properties, hydrophilicity, form, and biocompatibility for every distinct application. These characteristics are determined by the fiber's chemical composition, particularly its polymer structure.

The following are the primary factors influencing the polymer structure, which controls the duration of the medication and the pace at which the loaded drug is released:

1) Water-induced swelling of polymers

2) Drug-specific polymer selectivity

3) Rate of polymer decomposition

Additionally, the molecular weight of the polymer affects the fiber's thickness and physical durability, among other physical attributes.

Due to the direct correlation between a polymer's molecular weight and the viscosity of its solution at a constant concentration, molecular weight also influences the polymer concentration required for successful electrospinning¹⁸

Table 1. Polymers used in Electrospinning

Sr. No.

Category

Example

Synthetic based polymer

· Polyurethane (PU),

· Polyε-caprolactone (PCL)

· PolyL-lactic acid-co-polyε-caprolactone (PLACL),

· Eudragit-L

· Polyglycolic acid (PGA),

· Polyethylene terephthalate (PET)

· Polylactic acid (PLA),

· PolyL-lactic acid-co-polyε-caprolactone (PLACL)

Natural/biological based polymer

· Hyaluronic acid

· Cellulose

· heparin

· Collage

· Silk fibroin

· Chitin

· Alginate

5.2 ELECTROSPINNING POLYMER-SOLVENTS:

In electrospinning, polymers are usually dissolved in a suitable solvent before being spun into fibers. Selecting the appropriate polymer-solvent combination enables the production of nanofibers ranging from 10 to 2000 nm in diameter.

Table 2 provides examples of polymer-solvent systems used in this process³⁵

Sr. No.	Polymer name	Solvent
1.	Polybenzimidazole	Dimethyl acetamide
2.	PET	Trifluoroacetic acid/Dimethyl chloride
3.	PVA	Water
4.	Nylon 66 and nylon 6	Formic Acid
5.	Nylon-6-co-polyamide	Formic acid
6.	Polyimides	Phenol

5.3 SURFACTANTS:

Surfactants are now incorporated into the electrospun nanofiber production process to enhance the stability and solubility of active compounds in the electrospinning polymer solution¹⁹. They can be used individually or in combination with another surfactant. The specific surfactants are listed below:

a. Anionic Surfactant: Sodium Lauryl Sulphate (SLS).

b. Cationic Surfactants: cetyl trimethyl ammonium bromide (CTAB) and cetylpyridinium chloride (CPC).

c. Non- Ionic Surfactants: Pluronic F127.

6. DRUG LOADING:

Several methods are used to include medications into the electrospun fibers. The drug ralease profile is significantly impacted by drug loading, hence choosing the right loading technique for the intended use is essential²⁰. Various techniques for drug loading includes:

· A drug-polymer solution mixture.

· Coaxial electrospinning technique.

· Physical adsorption after the electrospinning process.

· Chemical surface modification after electrospinning

Figure-4 Diagrammatic illustration of several drug loading techniques: (a) physical absorption following electrospinning. (b) Blend of Drug and polymer. (c) Coaxial electrospinning and (d) Surface alteration using chemical means following electrospinning.

The simplest method involves dissolving the medication and polymer in an appropriate solvent and then combining the two substances directly. Blending provides the highest loading capacity compared to other methods. Together with the drug's solubility properties, the release profile will be influenced by the strength of the polymer-drug interaction. Achieving consistent release over a specified duration requires carefully balancing the hydrophobicity of both the drug and the polymer. The organic solvent, which commonly has the ability to denaturize bioactive compounds, is the primary cause of this technique's difficulties. Additionally, a burst release of the drug is typically seen²¹. A promising substitute is emulsion electrospinning, which encapsulates the drug inside micelles to produce core-shell nanofibers. Usually, a supernatant is added to a drug-containing water solution to form drug-containing microspheres.

A stable emulsion appropriate for electrospinning is produced by vigorously mixing the solution-created micelles with a polymer oil solution. There are two main advantages: First, reduced interaction between the bioactive molecule and organic solvent allows for the use of various hydrophilic drug and hydrophobic polymer combinations. Second, a uniform core-shell structure can be easily created without requiring specialized coaxial equipment.

Coaxial electrospinning is not only a method for creating core-shell nanofibers but also a loading technique. While it requires specialized equipment and optimization, it offers a wide range of polymer combinations for the core and shell, making it a flexible platform for loading various drugs into different fiber compartments. A key advantage of coaxial loading is that it positions the drug in the core polymer, with the shell acting as a physical barrier to prevent burst release. However, the main challenges of this technique are its difficult scalability and the need for precise parameter optimization.⁴¹

After electrospinning, the bioactive compound is protected from unwanted degradation by preventing interactions with the organic solvent. This also helps preserve the original mechanical properties and degradation of the polymeric matrix. However, achieving prolonged drug release requires strong non-covalent bonds and often a cross-linking process between the polymer and the drug^42,43,44.

7. APPLICATIONS IN PHARMACEUTICAL FORMULATION DEVELOPMENT:

Nanofibrous scaffolds, with their unique properties and easy tunability, offer a versatile drug delivery method for treating various diseases. Due to the diverse nature of illnesses, each application demands specific mechanical properties and drug release profiles. This section focuses on the primary and most widely studied use of nanofibers in drug delivery, discussing the methods employed for their fabrication and characterization, as well as their documented applications in the literature.

7.1 ANTIBIOTICS:

Bacterial infections, including sepsis, are among the most significant global health challenges, contributing to a high number of deaths worldwide. A major concern is antimicrobial resistance (AMR), which occurs when bacteria can grow despite the presence of antibiotics. By 2050, AMR is expected to cause 50 million deaths annually. Antibiotics are often used in combination to increase efficacy and reduce resistance, especially for chronic conditions like cystic fibrosis, which require long-term antibiotic cycles.

To address these issues, the development of more effective, adaptable antibiotic delivery systems is essential. Electrospun nanofibers, with their unique properties, offer a promising solution for targeted drug delivery, reducing the risks of overdosing and bacterial resistance by releasing drugs directly at the infection site. For example, Pisani (2019) developed gentamicin-loaded polylactidecopolycaprolactone electrospun nanofibers, which can help reduce bacterial biofilm growth after surgery. Gentamicin sulfate, an aminoglycoside antibiotic, is effective but has a low oral bioavailability and can cause renal and ototoxicity when administered intravenously or intramuscularly. The electrospun nanofiber system may minimize these side effects and enhance antibacterial effectiveness. The release rate study showed that the release of gentamicin was not related to polymer degradation, highlighting its delayed release potential.

In a different approach, Li (2020) explored a gastro-retentive drug delivery system using glucomannan polysaccharide from B. striata, combined with PCL electrospun fibers, for controlled drug release and enhanced stomach retention. This system, effective against H. pylori, a cause of chronic gastritis, demonstrated strong efficacy without cytotoxic effects. The high drug loading and sustained release made it a promising treatment option compared to free levofloxacin hydrochloride.

7.2 ANTI-TUMORAL DRUGS:

Cancer remains one of the most feared and prevalent diseases worldwide, despite significant advancements in treatment, diagnosis, and prevention. It is characterized by uncontrolled cell growth and the potential for metastasis. Early detection of malignant tumors before metastasis occurs significantly improves patient survival rates, enabling options such as chemotherapy or surgical removal of the primary tumor. Chemotherapy aims to halt tumor growth through cytotoxic drugs, such as doxorubicin, which induce apoptosis by disrupting the cell cycle. However, due to the tumor’s rapid growth and high vascularization, chemotherapy drugs primarily concentrate within the tumor but often cause severe side effects that impact healthy tissues.

To mitigate the toxic systemic effects of chemotherapy while maintaining its efficacy, localized drug delivery systems are being developed. Electrospun nanofiber scaffolds offer an ideal platform for controlled drug release due to their high tunability and excellent biocompatibility. For instance, Kuang (2018) developed electrospun scaffolds using a blend of hydrophilic poly (ethylene oxide) (PEO) and hydrophobic poly (L-lactic acid) (PLLA) to release doxorubicin in a biphasic manner. The first phase provided a rapid release of the drug to suppress the tumor, while the second phase ensured sustained release to prolong the treatment. The scaffold exhibited an effective release profile, and in vivo tests showed minimal damage and targeted biodistribution at the tumor site. However, the initial burst release of doxorubicin may not be sufficient for significant tumor suppression, and other polymer combinations might enhance the treatment's efficacy.

In a different study, Aytac (2020) used core-shell electrospun nanofibers, with PEO as the core and Eudragit S100, a copolymer of methacrylic acid and methyl methacrylate, as the shell. These fibers contained antitumoral drugs, such as 5-fluorouracil or ferulic acid, along with gadolinium as a contrast agent for magnetic resonance imaging. This setup allowed for combined tumor treatment and fiber tracking. However, the shell polymer's instability in acidic environments led to rapid drug release within two hours, highlighting the need for modifications to slow disintegration and enhance release control. Further research is needed to optimize these scaffolds for better stability and performance.

7.3 WOUND HEALING:

The skin, the largest organ of the body, serves key functions: sensation, regulation, and protection. As a barrier, it is vulnerable to injuries, playing a crucial role in defending against external threats and pathogens. Prompt wound healing is vital to avoid chronic infections and complications. Wound healing involves tissue regeneration and repair, influenced by internal and external factors. However, creating effective skin substitutes and wound dressings remains challenging.

For optimal wound healing, scaffolds must absorb exudates, mimic the extracellular matrix (ECM), and resist microbes. Electrospinning offers a promising method to achieve these characteristics. Additionally, scaffolds can incorporate active ingredients or medications to promote healing and deliver antimicrobial agents, reducing infection risk.

Varshosaz (2020) used double electrospinning technology to create wound dressing membranes from modified polybutylene adipate-co-terephthalate and gelatin nanocomposites infused with doxycycline. Polybutylene adipate-co-terephthalate is a biodegradable polyester with excellent mechanical properties, while gelatin helps mimic the ECM and control drug release. RGD peptide modification improved cell adherence. These membranes demonstrated antibacterial properties and promoted wound healing in vivo within three days without cytotoxicity. However, the polymer selection did not significantly improve the scaffold's mechanical properties, though the RGD peptide enhanced cell adherence.

Asadi (2020) sought to improve zein’s suitability for wound dressings by creating composite nanofibers with graphene oxide. Graphene oxide, which encapsulated tetracycline hydrochloride, improved the release profile and mechanical properties compared to zein alone. These composite scaffolds showed minimal cytotoxicity and excellent antibacterial properties, though no anti-inflammatory effects were observed. Both studies highlight the potential of electrospun scaffolds in enhancing wound healing and infection prevention, emphasizing the need for further optimization in scaffold materials and drug delivery systems.

7.4 OCULAR DISEASES:

Tears lubricate the eyes and help remove irritants, but treating eye diseases with eye drops has limitations due to poor bioavailability, small volume, rapid turnover of tear film, and physiological barriers. Solid delivery systems are gaining attention as they have lower system clearance and potentially higher bioavailability.

Tawfik (2020) developed coaxial electrospun nanofibers with two medications in separate compartments to treat corneal damage and bacterial infections. The outer layer was made of PLGA containing pirfenidone, while the center was made of hydrophilic PVP loaded with moxifloxacin. The nanofibers exhibited high drug loading, with a rapid release profile—70% of the antibiotic was released within 30 minutes, and pirfenidone fully released after 4 hours. However, the non-optimal interaction between the drug and polymer highlighted the need for further optimization, and the transparency of the scaffold, crucial for ocular applications, was not addressed.

Gottel (2020) used gellan gum electrospun nanofibers to create a solid in situ gelling system for treating eye diseases. The system was designed to bend into specific shapes, improving fiber contact with the eye and enhancing drug delivery. In a pig model, the fluorescein-loaded scaffolds showed more uniform dispersion and significantly longer residence time compared to traditional eye drops. While the study showed promising results, it only used a model chemical, and extended exposure to other medications could cause side effects. Additionally, the release kinetics were poor, and the required dosage for therapeutic effects was unclear.

7.5 ANTIHYPERTENSIVE:

Hypertension is managed with anti-hypertensive medications, but challenges like poor bioavailability and side effects can be addressed using electrospun polymer-based drug delivery systems. For example, Nifedipine tablets coated with poly (lactic-co-glycolic acid) nanofibrous sheets provide controlled release. The thickness of the sheet affects drug release timing. Biodegradable polyesters like PLLA, PLGA, and PLCL are used for sustained sublingual delivery of Captopril. Hydroxypropyl cyclodextrin and PVP are used for quick oral extraction of spironolactone. Additionally, electrospun polymeric patches with Timolol maleate and Dorzolamide hydrochloride effectively treat glaucoma by lowering intraocular pressure, reducing the dosage and side effects. These formulations control drug release, ensuring regulated delivery and reducing supersaturation

7.6 ANTIRETROVIRAL:

Biomedical professionals face significant challenges in combating HIV, particularly in developing effective treatments like microbicides for intravaginal drug delivery. Traditional gel-based systems for vaginal microbicides have limitations, such as being washed away by urine, reducing effectiveness. Electrospun nanofibers offer a solution, overcoming these limitations by creating drug-eluting fibers that deliver anti-HIV medications directly. However, issues related to drug vehicle deployment, retention, and sustained release need to be addressed.

Electrospun nanofibers, such as cellulose acetate phthalate (CAP) loaded with Tenofovir (TFV), offer controlled drug release, as CAP dissolves in the presence of human semen, releasing antiviral drugs. These fibers provide effective HIV transmission prevention while maintaining antibacterial properties. Additionally, polyvinyl alcohol and TFV electrospun nanofibers have improved drug loading and encapsulation efficiency, contributing to their potential as topical anti-HIV treatments. These advances have the potential to significantly impact HIV treatment and the development of fiber-based medical textiles.

8. CONCLUSION:

Electrospinning is an ancient technique that has recently garnered significant attention due to its potential for biological and nanotechnological applications. It produces nanofibers with a high surface-to-volume ratio, which makes it particularly attractive for drug delivery. This technique is not only cost-effective but also versatile, allowing for the creation of different nanofiber types tailored for specific drug delivery needs. Its ability to adjust nanofibers for particular applications has driven interest in using electrospinning for pharmaceutical purposes, offering innovative solutions for medication delivery. The main focus of electrospinning in pharmaceutical applications is to enhance drug stability, solubility, dissolution, and bioavailability. Nanofibers produced through this method can achieve high drug loading capacities and improve therapeutic efficacy. The process allows for the incorporation of both hydrophilic and hydrophobic drugs, and the flexibility of nanofibers can mimic the extracellular matrix of living cells, facilitating better interaction with biological systems. The result is a versatile and efficient drug delivery system that can be tailored for sustained release, enhanced drug absorption, and targeted therapy.

Despite its promising advantages, electrospinning still faces challenges in terms of in vivo research and application scaling. Although it is widely used in pharmaceutical applications, further exploration of the variables that control nanofiber synthesis and deposition is essential for advancing this technology. A deeper understanding of the electrospinning process will lead to improved drug delivery systems with more predictable and reliable outcomes. As this technology evolves, it holds immense potential to revolutionize the pharmaceutical industry by providing cost-effective, scalable solutions for drug delivery.

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Received on 24.05.2025 Revised on 18.09.2025

Accepted on 06.11.2025 Published on 15.04.2026

Available online from April 18, 2026

Asian J. Pharm. Res. 2026; 16(2):156-162.

DOI: 10.52711/2231-5691.2026.00024

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