Pharmaceutical Applications of Electrospun Nanofibers:

A State-of-the-Art Review

Mayuri M. Shitole¹, Shailesh S. Dugam¹, Neha D. Desai², Rahul S. Tade³, Sopan N. Nangare³*

¹Dept. of Pharmaceutics, Bharati Vidyapeeth College of Pharmacy, Kolhapur-416013,

Dist: Kolhapur (MS), India.

²Dept. of Pharmaceutics, Ashokrao Mane College of Pharmacy, Peth-Vadgaon-413112,

Dist: Kolhapur (MS), India

³Dept. of Pharmaceutical Chemistry, H. R. Patel Institute of Pharmaceutical Education and Research,

Shirpur-425405, Dist-Dhule (MS), India

*Corresponding Author E-mail: snangareopan@gmail.com

ABSTRACT:

Electrospinning is an advanced emerging technology in a novel drug delivery system. Principally it contributes major application in the pharmaceutical research field due to their versatility of electrospun NFs and productive utilization for the fabrication of drug-loaded fibers. Owing to the tailor-made and tunable properties of NFs such as high porosity, large surface area, superior mechanical properties, small pore size, and simplicity of surface modification, have a significant consideration to researchers. Electrospun nanofibers deal with the exceptional stability and biocompatibility of drug/ bioactive molecules. Besides, the spun process does not only improve the dissolution, solubility of active but also expanded bioavailability of poorly soluble drugs. Therefore, electrospun NFs are accomplished with the targeted, modified, and pH-dependent drug delivery systems. The current review article is an attempt to update the readers about the electrospinning process and spun nanofibers. Besides, this review is covered electrospinning types, parameters that affect the nanofibers, and the composition of nanofibers. Moreover, the key focus of this review is the utilization of electrospun nanofibers in pharmaceutical applications.

KEYWORDS: Electrospun nanofibers, Electrospinning process, Types of electrospinning, Pharmaceutical applications, Electrospinning.

INTRODUCTION:

Electrospinning (ES) is an efficacious route to the development of tailor-made electrospun Nanofibers (NFs)^[1]. Initially, the electrospraying method utilized for the production of polymeric droplets by using electrostatic forces^[2,3]. It is a derivative development as well as a kind of application of electrospraying^[4,5]. In 1934-1944, eleven patents were issued to Formhals on the account of ES. It provided different designs for the fabrication of terrific polymeric fibers^[1,6-11]. After that, In 1964 Geoffrey Taylor's investigation revealed the deformation of a water droplet by applying the electric field. In that, he claimed that the droplet converted into the conical shape; called Taylor cone^[12]. Another research of Taylors admitted the fine get using the appropriate viscous solution^[13]. In further eras, Annis and co-authors execute the challenging investigation and developed the electrospun polyurethane for probable vascular prostheses (the 1970s)^[14]. Also, in 1990 decades, the nano-size electrospun fiber development was taken a major account of research. Reneker and the team demonstrated the concept of physics prevailing construction of fibers^[1,15-18]. In essence, the ES is key terminology derived from the phenomenon of “electrostatic fiber spinning”^[19,20] or “Electrostatic Yarn” which gives the smallest fibers up to 10-100nm^[21]. Interestingly, the applied voltage offers the potential for the conversion of fine fibers to form a viscous solution/ polymeric melt. Herein, the decreasing diameter of electrospun NFs up to nanometer is an amazing and innovative approach for various pharmaceutical and biomedical applications^[4,19].

Electrospinning process:

ES is a promising technique in terms of simple, industrious, and promising nature. This technique has taken major holds on the development of drug/bioactive loaded spun NFs, especially for pharmaceutical applications. Usually, the process depends upon mainly three parts explicitly, high voltage power supply unit (a), a spinneret (b), and conductive collector unit (c)^[11,22]. On the other hand, it is an emerging trend in which the suitable viscous polymeric solution/melts/blends fills into the syringe and this prepared viscous solution is pumped for the fabrication of NFs by appropriate flow rate via suitable diameter of the needle. The optimized distance from the tip of the needle to the collector drum for NFs fabrication is incredibly important. Finally, the polymeric solution generates the Taylor cone/cone-shaped droplets at the tip of needles, and accordingly, Taylor cone converted into jet under the appropriate electric current^[23-25]. The schematic diagram of the ES is depicted in Figure 1.

Figure 1: Schematic presentation of the ES process

Herein, Polymeric droplet overcomes the surface tension for the ejection of polymeric electrospun NFs in the optimum electric field. Finally, these NFs are collected on the collector drum^[19,26]. During the fabrication of such superior electrospun NFs, the various forces involved like gravitational force, rheological force, aerodynamic force, inertial, and tensile forces^[22,27]. Also, due to inter-/intra-molecular interaction and excellent viscosity behaviors of ES solution, polymeric solution prefers for pharmaceutical/biomedical applications^[22,28,29]. ES technology provides phenomenal compensations for pharmaceutical applications such as flexibility to various polymers based methods, easy operation, and appropriateness towards the fabrication of spun NFs with tailor-made properties like diameters, structures, and textures, etc^[22,30].

Types of electrospinning:

The fabrication of flexible electrospun NFs is generally dependent on the type of ES process utilized^[24]. Herein, the common types of ES are reported, for example, emulsion electrospinning^[31], Melt electrospinning^[24], Gas jet electrospinning, Blend electrospinning and Co-axial electrospinning, etc.^[32].

1. Blend electrospinning:

Blend electrospinning is a widely accepted and conventional ES process. It’s based on the composition/blend of drug or bioactive molecules, which is dissolved or dispersed in the ES polymeric solution and spun for fibers generation (Figure 2A). These prepared NFs to provide the bioactive/drug is uniformly distributed throughout NFs^[32]. But, the utilization of a solvent in the preparation of blend/dispersion/solution may cause the bioactive denaturation leads to creates the burst release of molecules(drugs/bioactive)^[32,33].

2. Co-axial electrospinning:

Co-axial electrospinning overcomes the drawbacks of blend electrospinning. Principally, it is based on two nozzles that connect to the high voltage and two dissimilar solutions (natural/synthetic polymers, drug/bioactive molecule) which is filled into each nozzle (Figure 2B)^[32,34]. Briefly, the bioactive or the drug is filled into the inner get of ES and the polymeric solution is filled into the outer jet (co-spun). Consequently, the active entrapped into the core of NFs and polymeric solutions covered the core (shell) and due to that, it provides the sustained release of actives^[35]. As a result, this ES technique overcomes/ protect the denaturation of bioactive or proteins^[36].

Figure 2: Types of ES: A) Blend ES, B) Co-axial ES, C) Emulsion ES

3. Emulsion electrospinning:

Emulsion ES is analogous to the blend electrospinning. Generally, it is based on the composition of two immiscible solvent system viz. water/oil emulsion. This resulting emulsion shows the core and shell in spun NFs. In brief, the active with surfactant gives the W/O emulsion, after that the emulsion mixed with suitable polymers (natural/synthetic) and spun it for the creation of fiber (Figure 2C)^[32,34]. Subsequently, it converts into the viscous gradient and droplet enrichment in the axial region^[1]. Thus, the resulted NFs overcomes the initial burst release of active and offers sustained release of active^[32,37].

4. Melt electrospinning:

Melt ES is the conventional process of ES. Briefly, the polymer (natural/synthetic), drug, and other excipients melt into and extruded via capillary is called melt electrospinning (Figure 3A)^[38].

5. Gas jet electrospinning:

Principally, the gas jet ES is a type that provides an admirable improvement on conventional melt ES. It overcomes the temperature based limitations of melt ES. Briefly, the ES setup is connected with the gas jet assembly (Figure 3B). Herein, the co-axial jet is covered by heated gas, which provides sufficient heat to the NFs near the nozzle, and therefore the delay is occurring for NFs solidification^[32,39,40].

Figure 3: Types of ES: A) Gas-jet ES, B) Melt ES

ES parameters for fabrication of electrospun nanofibers:

The ES is a simplistic approach for spun NFs fabrication. But, several factors influence the size, shape, porosity, and uniformity of NFS. Herein, we have enlisted solution and solvent related parameters, processing, and environmental parameters in Table 1.

Table 1: ES parameters and its effect on spun fiber

Parameters	Effects
Solution Parameter	Molecular Mass	Higher molecular mass results in a more uniform morphology
	Concentration	Increases viscosity and amount of deposited nanofibers
	Viscosity	Increased viscosity fiber diameter increases and decreases bead formation
	Conductivity	Increasing conductivity fiber diameter decreases; ionic materials can reduce atomization of polymer jet
Solvent Properties	Vapor Pressure	During spinning; solvent evaporation may influence the formation of non-cylindrical morphologies
	Surface Tension	If the surface tension is considerable; bead formation may occur
Operating conditions	Applied Voltage	Decreasing fiber diameter with increasing voltage supply
	Distance of collector from nozzle	Fiber solidification; deposition area, increases with increased distance between collector and nozzle
	Solution Flow Rate	Higher flow rates = larger diameter fibers Lower flow rates = smaller diameter fibers
	Tip	Increasing tip diameter increases the diameter fiber
	Collector Type	Aligned fibers, yarns, braided, or random fibers can be obtained by changing from a plate to a drum, area, etc. type collector
Surrounding Conditions	Temperature	High temperature reduces the viscosity of the polymeric solution, resulted in a low diameter of fibers
	Humidity	High humidity resulted in the bead and circular pore formation in fibers, low humidity may produce thicker fibers due to quick solvent evaporation

Electrospun Nanofibers:

Extensive acceptance of electrospun NFs into pharmaceutical/biomedical applications is increased due to its tailor-made tunable properties as previously discussed. It includes superior mechanical properties, high surface area, and porosity, biocompatibility as well as biodegradability, etc. Furthermore, it improves the stability, dissolution, solubility and ultimately bioavailability of the poorly soluble drug. Besides, it modifies the drug release into controlled and sustained release, pH-dependent release, etc. Thus, this tune NFs having tremendous potential to overcome the problem of pharmaceutical drug delivery and various applications ^{[21, 41-44]}.

Excipients used in the electrospinning:

Fabrication of tailor-made electrospun nanofibers is based on single and multiple polymers, solvents, surfactants, etc. Based on the types of polymers; drug release, solubility, stability, mechanical properties, etc can be changed. The different types of solvent are used for the preparation of polymeric solutions such as an organic, inorganic solvent. Herein, the list of excipient was used in the fabrication of nanofibers are enlisted.

Polymers:

The polymers are a type of spun material, which is widely used for the fabrication of electrospun NFs for various pharmaceuticals and biomedicals applications. Lists of natural and synthetic polymers used in ES are enlisted in Table 2.

Table 2: polymers used in ES

Sr. No.	Categories	Example
1.	Synthetic polymer	Polyethylene terephthalate (PET), Polyε-caprolactone (PCL), Polystyrene, polyurethane (PU), Polyglycolic acid (PGA), Polylactic acid (PLA), PolyL-lactic acid-co-polyε-caprolactone (PLACL), PolyL-lactic acid-co-polyε-caprolactone (PLACL), Eudragit-L
2.	Natural/biological polymer	Chitosan (CS), Silk fibroin, Chitin, heparin, Collagen, alginate, Hyaluronic acid, and Cellulose

Polymer-solvents used in electrospinning:

The polymer is usually dissolved in a suitable solvent and spun from the solution. Nanofibers in the range of 10-to 2000nm diameter can be achieved by choosing the appropriate polymer-solvent system. Table 3 gives a list of some of the polymer-solvent systems used in electrospinning^[46].

Table 3: Polymer-solvents used in ES

Sr. No.	Polymer	Solvent
i.	Nylon 6 and nylon 66	Formic Acid
ii.	Polyacrylonitrile	Dimethyl formaldehyde
iii.	PET	Trifluoroacetic acid/Dimethyl chloride
iv.	PVA	Water
v	Polystyrene	DMF/Toluene
vi	Nylon-6-co-polyamide	Formic acid
vii	Polybenzimidazole	Dimethyl acetamide
viii	Poly-amide	Sulfuric acid
ix	Polyimides	Phenol

Surfactant:

In the fabrication process of electrospun nanofibers, nowadays the surfactants are utilized. It enhances the solubility and stability of active in ES polymeric solution ^[47]. It may be used in combination with/ two different surfactants. These listed below,

i. Anionic surfactant: Sodium dodecyl sulfate (SDS)

ii. Non- ionic surfactants: Triton X-100

iii. Cationic surfactants: hex-adecyltrimethyl ammonium bromide (HTAB), Cetyl-trimethyl ammonium bromide (CTAB/SDBS)

In this review, we have focused on a short discussion on the history, process, and types of ES. Also, we have enlisted various parameter effects on the ES and different excipients used in the fabrication and development of NFs. The core part of the review revealed the range of pharmaceutical applications of tailor-made spun NFs in the treatment of different health issues.

PHARMACEUTICAL APPLICATION OF ELECTROSPINNING:

From past decades, ES is raising many researchers’ attention towards the spun NFs and fruitful properties of NFs. Numerous reports explored the application of fibers in a novel drug delivery system (NDDS) to various intentions. Owing to its revolutionary properties ES, it holds the most imperative credit account of the pharmaceutical field for delivery of antibiotics, antioxidants, anticoagulants, proteins, enzymes, hormones, analgesics and wound dressing/healing, etc.

Antimicrobial agent loaded NFs:

Electrospun nanofibers show good bactericidal activity because of anti-biotics loaded within. Electrospun nanofibers often show a high initial burst release, which affects the antimicrobial performance over an extended period. To reduce the burst-release profile and gives sustain antimicrobial activities for local treatment of periodontal disease fibers were cross-linked. Based on such cross-linking intentions, authors were prepared metronidazole-loaded resorbable polylactide (PLA) electrospun NFs. Interestingly, prepared NFs offered the sustained drug release properties up to 28^th day and due to that, it showed exceptional antibacterial efficacy plus it resulted in excellent biocompatibility and cytocompatibility. Thus, it could be an open new route for clinical application in the management of local periodontitis disease^[48]. Similarly, cefoxitin sodium (Mefoxin), the hydrophilic antibiotic was successfully encapsulated into the poly (lactide-co-glycolide) (PLGA)-based nanofibrous scaffolds using the ES without the change of its structure and bioactivity. The drug-released study revealed that the scaffold releases a maximum amount of drug after 1 hour at physiological temperature.The amphiphilic block copolymer poly (ethylene glycol)-b-PLA (PEG-b-PLA) gave the less cumulative release and retards the release up to 1 week, along with that it showed excellent antibacterial activity. Thus, it could be more useful with the combination of mechanical barriers based on non-woven nanofibrous biodegradable scaffolds in biomedical applications and especially for, post-surgical adhesions and infections preventions^[49]. Recently, polymeric NFs for drug delivery is challenging for biomedical/ pharmaceutical applications, but a convenient dosage form is taxing for a scientist. Alternative like transdermal dosage form having huge drawbacks such as solvent spreadability, retention of dosage form, and antibiotic resistance due to that, the authors have investigated the fluconazole loaded Eudragit L100 (EL100) NFs entrapped gel for topical application. Significantly, outcomes showed a noteworthy modification in the release as well as antifungal activity. Thus, it could offer a new route for NFs based topical dosage form development^[50]. Electrospun NFs showed exceptional significance like slow and stable degradation nature and owing to this it provides the slow vancomycin release from vancomycin loaded PLGA scaffold. It showed the admirable and effective antibacterial activity for methicillin-resistant staphylococcus aureus. Besides, this scaffold showed the site-specific bone regeneration rate enhancement and therefore, it could be used in the infected bone defects management^[51]. Ciprofloxacin HCl (CF) loaded alginate NFs showed that Poly (ethylene oxide), (PEO) played a major role as carrier polymer. The PEO chain enhanced the chain entanglement and carried alginate in ES solution during the process of ES. Moreover, the addition of surfactant into the solution gives the surfactant and polymer interaction a, which reduces the surface tension and suppresses the bead morphology of electrospun NFs. Thus, such a type of novel scaffold could be potentially used for drug delivery, wound healing process, and regenerative medicine^[52]. Levofloxacin and irgasan loaded PCL electrospun NFs were prepared for hernia repair situation. Authors were claimed that, the increase in voltage offers the enrichment of NFs diameters. The addition of irgasan and levofloxacin into the solution of polymers and drug effect on the flow properties like reducing the shear viscosity, elastic and viscous modulus and enhanced the hydrophilicity of NFs. Thus, it concludes that drugs alter the internal morphology of the polymer. Besides this, irgasan showed the molecular diffusion based sustained release from a scaffold, and due to the phase separation; the levofloxacin may entrap at the edge of NFs and showed the burst release with antibacterial activity. So, it could provide feasible attention to the treatment of hernia^[53]. For the treatment of root canal infectious pathogens like candida Albicans and Enterococcus faecalis, the 2% chlorhexidine (CHX) showed the exceptional capability of antimicrobial activity. For admirable activity against such type of pathogens, authors have reported the poly(vinyl)alcohol (PVA) based NFs with 2% CHX in the management of root canal infections and compared with gel and solution form of 2% CHX. The prepared electrospun NFs offers the smooth, linear and continuous spun NFs. Release kinetic of prepared fibers showed the diffusion and hydrolytic degradation of PVA. Furthermore, the matrix pattern-based fibers showed the initial burst release and these prepared effective as similar to the gel form^[54]. The antibiotic, CF and its antimicrobial oligomer (AO, two molecules of CF connected by triethylene glycol), were successfully entrapped into the scaffold of polycarbonate urethane (PCNU) NFs and subjected for antibacterial activity and cell compatibility. In brief, the CF could change the fiber diameter by varying the viscosity of the solution and PCNU can maintain the viscosity of the solution. Besides, the CF and AO NFs showed the higher stability of spun jet, elongation forces, yield, and uniformity of spun NFs. As, the surface segregation of AO occurred, it provides a rapid and high amount of drug release at a high concentration of AO. Thus, it could be used in local applications for tissue engineering which could prevent biomaterial related infections^[55]. Kuntzler and co-author were revealed that the utilization of microalgal origin polyphenolic compounds like caffeic acid, salicylic and gallic acid, etc. for antibacterial activity in the form of the electrospun NFs. For the preparation of NFs, authors have selected the most significant polymer like CS-PEO. The entrapment of the phenolic compound showed the stability inside the NFs and showed excellent antibacterial activity, which is concentration proportional. Besides, the high concentration of CS shown the entanglement, and consequently, it overcomes the surface tension of at the capillary tip and finally smaller NFs were obtained. This uniform, small, and hydrophilicity of spun NFs help to the antibacterial activity^[56]. Encapsulation process of silver sulfadiazine (SSD) in β-cyclodextrin (β-CD) offered the modification of solubility, dissolution, drug loading ability, drug release, and reduces the toxicities. This complex was entrapped into the PVA spun NFs, after that the release from NFs was significantly increased due to the physical and chemical changes of SDD. Also, it showed excellent antimicrobial activity due to the increase in the surface area of silver. Besides, the hydrogen bonding between PVA and β-CD increased the viscosity and subsequently it reduces the diameter of NFs. Thus, it concludes that it could be used in drug delivery as well as tissue engineering applications^[57]. Norouzi and co-authors have fabricated the salinomycin loaded PLGA based NFs. This prepared spun NFs showed the absence of weight difference in NFs when a change in parameters. The drug release from the spun NFs surface showed the diffusion-based drug release mechanism and after this, the second stage is polymer degradation. This prepared NFs showed that the more U251 glioblastoma cells killing efficiency, superior reducing capacity to the reactive oxygen radicals and improved cytotoxicity, etc ^[58]. Yet one more work demonstrated that the use of Emblica officinalis (EO) loaded PCL-NFs by the ES process. Briefly, the entrapment of EO in NFs showed the rough surface morphology and the average diameter of spun NFs was increased with an increase in EO concentration. Also, owing to the presence of functional groups in extract increased the zeta potential with an increase in the concentration of EO. Finally, it showed significant antibacterial activity and the EO scaffold was inhibited cell proliferation^[59]. Antibiotics resistance is today's key issue and apart from the synthetic various natural products showed excellent wide spectrum activities. Recently, the Bidens pilosa leaves extract was blend with CS and PVA and fabricated the fiber by ES. Various quality attributes were showed a significant impact on the spun NFs like an increase in voltage more than 18kV, low rate reduction showed the bead morphology and unpredictable size of NFs. The low concentration of polymer was found to unable to maintain stable jet, from Taylor cone to fiber collector. Owing to this, the bead morphology was observed. After that, the cross-linking in NFs showed a high swelling capacity as well as low weight losses. Finally, it showed exceptional antibacterial activity and due to that it could be potentially applied for an alternative of synthetic drugs in microbial resistance^[60]. However, one more work explored the application of PCL NFs for the encapsulation of ascorbyl palmitate (AP). The deposition of AgNPs in this mat showed the reduction of silver ions. The authors were reported that the high concentration of AP showed a small diameter and it does not depend on the viscosity of ES solution. Furthermore, this mat preserved the stability of antioxidant activity and showed an admirable antibacterial and antioxidant activity^[44]. Hence, delivery of antimicrobial agent via spun NFs it could be an effectual alternative for marketed engaged ones.

Anticancer agent loaded NFs:

To cure and control cancer, a variety of studies have been performed to develop new therapies and delivery methods for established therapies^[61,62].The aforesaid discussed properties of ES NFs support them to be used as the best platform for cancer cell applications. Recently, gene silencing using siRNA delivery has gained more attention and it leads the new biomedical applications such as cancer treatment, infectious disease, and genetic disorders, etc. In brief, siRNA was encapsulated in the PCL and prepared the electrospun NFs. It showed the controlled release of siRNA at least for 28 days. The encapsulated siRNA showed excellent stability and activity in over release period. In contrast to conventional transfection, it showed the 61–81% silencing efficiency. Hence, such type of scaffold-based siRNA local delivery enhanced the gene silencing as a contrast to the passive uptake and absence of transfection agent. As a result, it could be used for gene-silencing as the potential of a nanofibrous scaffold for siRNA delivery to the long-term applications^[63]. M. Javadian and co-authors were reported the copolymerization of PLA-PEG-PLA, which offers excellent material for NFs as compared to the PLA. This copolymerization improved the PLA hydrophilicity, degradation rate as well as crystallinity. Subsequently, the PLA-PEG-PLA tri-block utilized for tamoxifen loading into by ES. Experimental findings showed the victorious integration and uniformity of drugs in electrospun PLA-PEG-PLANFs and finally, the copolymerization of PLA showed the sustained release of tamoxifen^.[64]. Qi and co-authors have demonstrated the use of doxorubicin (DOX)-loaded multiwall carbon nanotubes (MW CNTs) encapsulated into PLGA. In that, the MW CNTs showed excellent stability as well as maintain the 3 D structure of NFs. Besides, it offers a double container for drug delivery leads to no initial burst release. Moreover, it provides the ability to deliver the DOX to the target region like a tumor. Consequently, such type of drug delivery system could be most promisingly used for post-operative local chemotherapy as therapeutic scaffold materials^[65]. Recently, the DOX loaded-PLA and pearl powder (DOX@PLA/pearl) blend were successively spun and converted into the NFs by ES process. The pearl powder provides unique surface morphology and homogeneity. Besides, this powder showed the reduction of hydrophobicity and it enhanced the hydrophilicity of PLA-pearl composite of DOX and due to this, the rapid release of DOX carried out. This scaffold showed the appreciable result for antitumor activity, which is more superior as compared to the plain PLA load DOX. Thus, it could be more suitable for postoperative cancer treatment^[66]. Pancreatic cancer is a leading cancer type and it has poor prognosis techniques and treatment. Therefore, authors fabricated the Poly-L-lactic acid (PLLA)-based NFs for delivery of fluorouracil (5-FU) and gemcitabine individually and combine form. This drug-loaded electrospun NFs showed low systemic toxicity and excellent potential towards the tumor treatment. The combined form of a drug-loaded NFs patch showed the more effective as compared to the single ones^[67]. The development of dual drug-loaded NFs for cancer treatment is an interesting field for the researcher. Furthermore, various factors including drug solubility, solvent properties, drug interaction towards the drug and polymers, and various parameters of the process of ES. Herein the silk fibroin (SF) was used for the preparation of core of curcumin nanosphere and DOX was entrapped into the shell and dispersed SF solution spun. Prepared NFs showed the effect of drug concentration on electrospun NFs. Furthermore, depending on the encapsulation of drugs into NFs, the DOX was released first, and then curcumin subsequently by diffusion mechanism. The crystallinity of NFs showed the limit for swelling and then, diffusion rate^[68]. Khashi and co-authors were prepared for the drug-eluting stent by ES technique. In brief, the taking of advantages of PLA and CS for the development and delivery of anticancer agent paclitaxel. CS controls the drug release from NFs after the initial burst release. It showed low cytotoxicity as well as resist cell adhesion and antiproliferative activity after an increase in drug concentration. In the future, it could be an open new era for the development of new polymeric stent^[69]. Recently, authors were prepared alginate NFs based gelatin/polylactic acid/Curcumin (GL/PLA/Cur) implantable scaffold. Authors were claiming that the wettability of NFs provides the adhesion, cell proliferation. Furthermore, the high wettability showed the initial burst release. This scaffold showed excellent wettability and it sustained the release for 15 days, also it offered better fibroblast cell growth. Based on productive outcomes, it could be used in cancer therapy, wound dressing, and drug delivery^[70]. The photothermal and chemotherapy is more important in cancer treatment. A chemotherapeutic agent is having extreme toxicity for cancer as well as normal cell and photothermal agent having low accumulation and poor degradation. So, there is a need to overcome such a major exigent problem. Hence, the authors were prepared the DOX (a chemotherapeutic agent) and molybdenum disulfide (MoS₂) based CS-PVA NFs (CS/PVA/MoS2/DOX) for cancer treatment. These NFs showed admirable photothermal efficiency and biocompatibility for In vitro and In vivo applications. Furthermore, prepared NFs showed the sustained release of DOX and excellent efficacy towards chemotherapy. Finally, based on such abundant outcomes, it could be used in the combined form more potentially and it could be used as a promising option for biomedical application^[71]. Chen and co-authors were reported the utilization of titanocene dichloride loaded PLLA NFs in chemotherapy. These spun fibers showed the controlled release of titanocene dichloride and enhance the safety and efficacy of chemotherapy. So it could be used for malignant tumors as an implantable device^[72]. Thus, based on the exceptional outcomes of presented reports spun NFs could be hopeful to the pharmaceutical applications for the delivery of anticancer agents in the treatment of life-threatening cancer.

Anti-inflammatory agent loaded NFs:

Anti-inflammatory drugs reduce inflammation and swelling signs^[73] and may have analgesic and antipyretic effects. These drugs have been earlier used in ES because of various kinds of pharmaceutical constituents. Since spun polymer, PVA having exceptional advantages such as hydrophilicity, release modifying capacity, biodegradability, and cost-effectiveness and due to that consideration, the utilization of PVA in drug delivery has taken vital significance. Herein, using the innovative ES techniques, ketoprofen loaded PVA NFs were successfully prepared. In that, the stability of NFs was enhanced by alcohol treatment and this vapor treatment enhances the crystallinity of PVA fibers and retarded the release up to 2 weeks as well as diminished the initial burst release. As a conclusion, it observed that the release of Ketoprofen from electrospun NFs is depended on the hydrolysis of PVA NFs^[74]. Yet one more revealed the utilization of PVA in the drug delivery of Meloxicam. In brief, Meloxicam has major limitations like low dissolution, permeability, and solubility. For overcoming such types of limitations, the authors have selected the ES as a platform. Finally, Meloxicam loaded PVA mats and normal film casting showed a noteworthy difference. The prepared spun fibers showed a high degree of swelling, weight loss, and skin permeation parameter than the film casting. Based on the finding of works, these prepared mats could be more suitable in transdermal drug delivery applications ^[75]. Meng and co-authors have explored the ES application in the preparation of nanofibrous scaffolds of Fenbufen loaded poly (d, l-lactide-co-glycolide) (PLGA) and PLGA/GL. These prepared NFs showed the modified controlled release of Fenbufen. The addition of GL into the PLGA enhanced the hydrophobicity and increases the release rate as well as eliminates the initial burst of Fenbufen. Besides, the glutaraldehyde vapor treatment to NFs retards the release of Fenbufen. Furthermore, the pH of the buffer solution showed an effect on the physical state of the polymer matrix and it alters the release rate, also, the prepared scaffolds are more stable at various pH as compared to the film casting method ^[76]. Acid liable polymers synthesis has more importance for the local targeting application. Herein, the authors synthesized the acid-labile co-polymer using the 3,9-dimethylene-2,4,8,10-tetraoxaspiro [5.5] undecane (DMTU) with PEG and copolymerized with D, L-lactide. Thus, the biodegradable and acid-labile co-polymer was electrospun with paracetamol. Besides, these prepared NFs controlled the initial burst and release rate^[77]. Colon targeted drug delivery system of indomethacin is a challenging arena for the drug delivery system. The present investigation revealed the ratio of pH-dependent [Eudragit S100 (ES 100)] and time-dependent [Eudragit RS100 (ERS100)] polymers in a single matrix for indomethacin colonic drug delivery. Polymeric ratios for fiber affected the release behavior and increasing the ERS 100 lowers the burst release.The finding of pH and time-dependent polymers showed the limited release of drug in pH 1.2, Then it was sustained at pH 7.4^[78]. Nikkola and co-authors have successively explored the application of Poly (D, L lactide-co-glycolide) 80/20 (PDLGA80/20) in ES for the intention of diclofenac sodium delivery. During the experimental process, it observed that the low molecular weight ester-based polymer is more suitable for scaffold due to its biodegradable nature; furthermore, it showed the fast drug release as compared to the high molecular mass. Also, the ions of solvent and polymer and drug showed a significant effect on the process of ES. Thus, the PDLGA80/20 provides slow degradation and prolongs the release^[79]. Those drugs are having the absorption window from the stomach, for that the gastro-retentive drug delivery system is more suitable. Similarly, diacerein has the absorption window from the stomach region and due to that, the authors prepared the diacerein loaded PLLA NFs. Outstanding finding from the investigation was reported that the diameter of fibers get changed after addition of drug into the polymeric solution and it may be the change of viscosity of the solution. Furthermore, these drug-loaded NFs showed the lessen swellability due to the reduction of porosity compared to the plain ones. Besides, increase the surface area of NFs increases the solubility of drug-loaded NFs in respective media. Smallest diameter NFs showed the admirable tensile strength and lower mechanical strength. Besides, the decrease in the surface area, increase the diameter and density of fiber showed lessen the mucoadhesive force. As a result, it concludes that the ES process improved dissolution, solubility, and permeability of drugs^[80]. According to the aim of work, authors fabricated the GLNFs as a hydrophilic carrier for hydrophobic drugs. In brief, the piperine was loaded into the GLNFs and enhanced the cross-linking by glutaraldehyde (25% v/v) vapor. After that these prepared NFs were checked for stability and release profile. It was revealed that stable hydrophilic NFs of GL, also, prolonged the release of piperine, as well as pH-dependent release, can be possible for a specific side. Along with that, it demonstrated that the cross-linking of GL-NFs is a major factor for the release of piperine^[81]. Maslakci and co-authors were demonstrated the use of PVP-Dextran blend for the formation of ibuprofen and acetylsalicylic acid electrospun NFs for wound dressing application. It showed the drug content of ibuprofen is more as compared to the aspirin. This blend of dextran provides the more uniformity in the size because of the reduction of the charge density of PVP. Moreover, the dextran in the PVP-drug solution gives the solubility enhancement. Finally, this prepared NFs was subjected to antibacterial testing. It showed superior antibacterial activity. Thus, it could be potentially used as a drug-loaded mat for wound dressing application^[82]. Cellulose acetate (CA) had suitability for human use due to its non-toxic nature. Herein, the successful attempt has been made to synthesize the CA loaded Tetracycline HCL as a model drug. These prepared fibers showed the excellent bead free NFs forming and ES stability at the specified concentration in acetic acid-acetone (3:1). Additionally, it exhibited excellent water uptake capacity. Moreover, it showed noticeable antibacterial activity and inertness for fibroblast cells. Accordingly, the 14% CA drug-loaded NFs could be more appropriate for the wound dressing application^[83]. Vatankhah has enhanced the bioavailability of poorly soluble herbal NSAIDs, rosmarinic acid (RosA) drug by loading into CA NFs. It was observed that the RosA converted to crystalline to amorphous form during the ES due to the polymeric chain interaction with RosA. It showed the high drug loading, high amount and prolonged release, low burst release. Besides, it improved cell viability. This sustained-release spun NFs can be a potential candidate for the transdermal patch for the delivery of anti-inflammatory and antioxidant^[84]. Yet one more work explored the application of ES for the drug release system. Briefly, Diclofenac is having the capacity to induce cell death, but it is used in various serious health issues management. Herein, the diclofenac induced in the PLA NFs provides the sustained as well as controlled release. Moreover, the addition of co-solvent offered the change in the drug release, morphology and burst release. To conclude, these NFs could be used as a diffusion controlling aid for encapsulated bioactive^[85]. Thus, NFs enhanced the solubility, dissolution, bioavailability of drugs, and modified the drug release. Thus, ES could be open a new path to the delivery of the anti-inflammatory drug.

Protein delivery using NFs:

The DNA, RNA, proteins, and growth factors, etc are among the most widely loaded bioactive materials in electrospun fibers. The ES method applied to the bioactive materials should be engineered to maintain the material performance and functional efficacy. Therefore, protein delivery holds the major account in biochemical signaling for tissue engineering. Taking into consideration as well as advantages of ES and polymers, the human nerve growth factor (NGF) was stabilized by bovine serum albumin and successfully entrapped into the copolymer NFs of PCL and Polyphosphate (ethyl ethylene phosphate) (PCLEEP). It sustained the NGF release up to 3 months. It observed that the coaxial ES increase the loading of NGF and activated for 3 months and even at a low concentration. Accordingly, it could offer outstanding potential for peripheral nerve regeneration^[86]. Interestingly, bovine serum albumin (BSA) loaded PVA NFs were successfully prepared. These prepared PVA NFs have shown the fast protein release in normal physiological conditions. Simultaneously NFs were coat with Poly (p-xylylene) (PPX) and polymeric layering, authors claimed that the various parameter which is more significant for the change the release of protein such as polymers type, molecular weight, crystallinity and coating polymers, etc.^[87]. Thus, the ES process could offer an innovative pathway for the delivery of protein to the treatment of various disorders.

Analgesic delivery using NFs:

Development capsaicin loaded PVA-NFs for transdermal drug delivery showed that the increase in the concentration of capsaicin increases the release rate due to the reduction of the PVA diffusion barrier. The prepared NFs showed superior tensile strength and release rate as compared to the film casting^[88]. Taking into the consideration of PEO and sodium alginate, authors were prepared the PEO and sodium alginate spun fiber for the delivery of lidocaine (local anesthetic) to the management of nerve pain for burn condition. Lidocaine loaded NFs showed less amount of liquid adsorption, but it is admirable to the wound condition. As a result, these NFs showed the burst release and 60% release of lidocaine within 10h. Thus, it could be useful to burn patient pain treatment conditions^[89]. Yet another work investigated the PEO/Sodium alginate-TritonX-100 (PEO/SA-T) electrospun NFs for delivery of acetaminophen. Principally, the addition of drugs in the ES solution showed a decrease in the final diameter. Besides, the increase in voltage up to a certain limit provides the smooth fiber and after that, defect the NFs and bead morphology occurred. Finally, it showed the fast release of acetaminophen, good liquid adsorption capacity, etc. Thus, the analgesic agent loaded NFs could utilize as a promising solution for local analgesia in burn wound cases^[90].

Antioxidant loaded NFs:

Antioxidants play a crucial role in the prevention of organ or tissue from the toxic free radicals^[91,92]. The free radicals example like hydroxyl ions generates severe toxicity to the body system like tissue necrosis^[93], for example like wound healing case^[94,95]. Thus, there is a huge demand to deliver the anti-oxidant to the target site. Herein, the ES process is effectively utilized in vitamin C loaded NFs preparation. In that, the authors claimed that the use of vapor treated SF for NFs offered the water-insoluble properties and showed the swellability after 4 days and it depends on the ability of mats including facilitating the skin tissue absorb and maintain the water, porosity and high specific surface area. Thus, such pioneering and abundant spun fibers could be used for the skincare application as well as wound dressing application and delivery of polar vitamin C^[96].

Application of NFs Wound Healing and dressing:

Wound healing route taking a huge account of well-organized biological and molecular dealings like cell proliferation and migration, angiogenesis, extracellular matrix deposition, and remodeling, etc^[26,97]. Fabrication of suitable and admirable tailor-made material for wound healing is a prominence arena for pharmaceutical and biomedical applications^[26,98]. The various reports have been successively explored the application of drug/ bioactive loaded in electrospun NFs and these NFs showed the exceptional capacity to cure the wound. On the account of the wound dressing, the present investigation explored the utilization of PVA, poly (vinyl acetate) (PVAc) for the preparation of NFs mats using the ES process. Successfully, CF-HCl was loaded into the mats and subjected to the evaluation. It showed that the CF-HCl concentration into PVA and PVAc decreased the viscosity of the solution and it gives the smaller diameter of the electrospun fiber. Also, the variety of polymer and amount of drugs present into polymer influenced the performance of drug release; the degree of swelling, initial burst, and weight loss^[99]. Yet one more investigation demonstrates the fabrication of lysozyme loaded with CS-ethylene-diamine-tetra-acetic acid blend mixture (CS 2 wt %–EDTA) along with those PVA NFs (CS-EDTA-PVA) by ES. It that, the increase in the concentration of enzyme decrease the loading capacity of NFs and the rapid release occurred and it depended on the enzyme content that existed in the NFs. The release mechanism involved in NFs was polymer erosion and enzyme diffusion. Besides, the cytotoxicity study revealed that the increase in mat mass decreased cell viability. Moreover, it showed the accelerated wound healing ability in animals. Thus, it could be potentially used in wound dressing^[100]. Taking into consideration the biomedical application of NFs in wound healing, the HR-TEM showed the successful entrapment of AgNPs into the PVA electrospun NFs. These AgNPs stabilized by the PVA and avoid agglomeration. High voltage offered the electron transfer of oxide reduction reaction for OH and Ag^ and electrified the droplet at nozzle droplet. Moreover, the same reaction was observed in the evaporation of water and elongation of the jet.Besides, the mat showed the biocidal activities, so it could be potentially used in the wound dressing^[101]. Burn wound management having essential eminence in the biomedical arena, especially scaffolds and dressing which control, reduces the inflammation. Herein, a successful attempt has been made to develop the polypropylene fumarate (PPF) loaded poly (octyl cyanoacrylate) (POCA) electrospun fiber for dressing. It showed an exceptional anti-inflammatory activity as well as accelerates the healing rate. Thus, it could endow the effectual alternative for burn healing^[102]. Alavarse and co-authors prepared for the PVA/CS/Tetracycline HCl mats for wound dressing. Owing to cross-linking and three-dimensional nature, it offered various advantages like stability and modified the release. This scaffold provides the sustained release of tetracycline with excellent antibacterial as well as cytocompatibility, so it could provide the alternative for wound dressing^[103]. Tetra-hydro curcumin (THC) showed wound healing capability due to the antioxidant, antibacterial and anti-inflammatory activity of THC, etc. Herein, the high molecular weight PVP and THC blend were spun and checked for dissolution activity. It showed the 91 percent release within 5 min, due to the hydrophilicity and hygroscopicity of PVP. The conversion of amorphous form and dissolution properties offer the alternative in the buccal patch for the treatment of mouth ulcers^[104]. To avoid causing the agent of bacterial infection in the wound is the major tasking field for researchers. The medicinal plants having excellent antimicrobial activity and it can be more capable with a suitable carrier for wound treatment. Herein authors have fabricated the Tridax Procumbens extract loaded PCL NFs by ES technique. These prepared spun NFs shown the wound healing activity along with treated the surface pathogens gram-positive and negative bacteria. Thus, experimental data revealed that it could be utilized in wound dressing applications using natural drug delivery ^[105]. Yet one more work revealed the use of natural protein (SF) and oleuropein (active from olive leaf) for wound treatment. In brief, during the preparation of the spinning solution oleuropein shown the in situ acid hydrolysis and it gives the excellent antimicrobial agent, hydroxytyrosol. Principally, the hydroxytyrosol loaded SF NFs showed the outstanding antimicrobial activity. Thus, it may be used in the biomaterial for wound dressing^[106]. Delivery of bioactive in wound dressing via electrospun NFs is an attention-grabbing area in biomaterial application. Herein, authors were prepared the platelet-derived growth factor (PDGF) loaded CS-PEO/Fibrinogen (CS-PEO/Fb) scaffold by ES. The PDGF sustain release encourages the fibroblast migration and consequently, wound healing. Thus it may prove the excellence of scaffold in the wound treatment application by the delivery of bioactive^[107]. Kurecic and team were revealed that the stable and biocompatible carboxy methyl cellulose (CMC)-PEG NFs with diclofenac (model drug) for wound healing and tissue regeneration. Furthermore, it controlled the release of diclofenac from NFsup to 48 hrs. Additionally, it showed the biocompatibility and no toxicity on skin fibroblast cells. Consequently, non-invasive behaviors, it could be used potentially as smart drug delivery NFs for wound healing^[108]. Yet one more investigation revealed the use of electrospun NFs ineffective wound treatment. In that, the CF-HCl (CHL) and quercetin were successfully loaded into the PCL NFs. It was observed that entrapped actives converted into amorphous without any interaction between drug and excipients. Moreover, it showed the high loading capacity, suppressed the infection as well as oxidative damage which confirmed by antioxidant and antibacterial activity. Wound induced animals were subjected to the wound healing study and it showed the exceptional enhancement of reepithelialization and collagen deposition evinced it can furnish the admirable potential in wound dressing textile ^[109]. Locilento and co-authors prepared the rich antioxidant source grape seed extract (GSE) NFs loaded with PLA and PEO by ES techniques. The PLA-PEO-GSE showed the higher control release of GSE than the individual PLA-GSE NFs. Furthermore, PLA-PEO-GSE NFs showed superior cell attachment and proliferation ^[110]. Consequently, the NFs mat/scaffold could be used as a potentially revolutionary material in wound dressing and wound healing process.

Enzyme loaded NFs:

Enzyme loaded NFs is an upcoming approach in the arena of pharmacy, in that the various parameters take challenging attention including enzyme activity and stability during the process and after fabrication of NFs. Herein the present investigation explored the application of PVA NFs for the delivery of enzymes. In brief, the luciferase loaded PVA NFs showed the initial burst release, and the PPX coating of NFs shown a significant effect on the release behavior of enzymes from PVA NFs. Thus, it concludes that the initial burst could be avoided by using the coating phenomenon, and release can be retarded for a long duration^[87]. Since, the chitosan has a major account in wound healing, the increase in the concentration of PVA on the blend of CS provides a smaller uneven diameter. Finally, the optimized blend of CS and PVA mixture loaded with ampicillin. Owing to the outstanding antibacterial activity, this enzyme laden spun NFs could be a potential candidate for the delivery of respective enzymes in the treatment of different ailments^[111].

Antispasmodic agent loaded NFs:

A list of antispasmodic agents available to the management of various health issues. But, most of the molecules having poor aqueous solubility, crystalline nature, and due to that bioavailability problem. To overcome aforesaid limitation herein, the antispasmodic agent, mebeverine HCl was encapsulated in the PVP and Eudragit L100-55(EL100-55). These electrospun NFs showed a fast-dissolving and sustained drug delivery mechanism. In that, the PVP drug-loaded NFs showed rough surface morphology and Eudragit drug-loaded NFs showed the unstable, short fragments. The spectroscopic study revealed the conversion of mebeverine HCl from crystalline to amorphous nature. Moreover, authors have claimed the dissolution study PVP NFs provide the fast release due to the hydrophilic nature of PVP. Simultaneously, Eudragit based NFs showed the pH-dependent sustained release, and consequently, these drug-loaded fibers could be constructive in the advanced suppositories for local treatment^[112].

Anticoagulant loaded NFs:

Generally, patients administered with anticoagulants to avoid thrombosis^[113] of the deep veins or pulmonary embolism. Nonetheless, due to many problems in anticoagulant treatment, much attention has been paid to the development of an ideal anticoagulant and several attempts have been made in the last year to create a new anticoagulant delivery system. Fascinatingly, dipyridamole release was controlled using the blend/ mixture of PCL-PEG. The prolific result of this experimentation showed the significance and impact of PCL-PEG in ES. Due to the existence of PEG, the solution homogeneity increased and the surface entrapment of dipyridamole occurred. Thus, for diffusion-based sustained release of active, the PEG could be more useful^[114]. Therefore, such anticoagulant laden drug delivery could be used for overcomes the demerits of conventional drug delivery.

Antihypertensive loaded NFs:

Hypertension, currently a global problem, is not in itself a condition but an important risk factor for severe cardiovascular problems including myocardial infarction, stroke, heart failure, and peripheral artery disease^[115]. While several medications are available on the market as a traditional for the management of hypertension, they face major challenges in terms of their bio-availability, adverse effects, etc^[116,117]. The low solubility of irbesartan is a major limitation for the dissolution and bioavailability, thus by ES process, the Irbesartan was loaded into the PVP k90 and it gives the 6.05 times more saturation solubility. Also, these NFs showed the 2.5 times more dissolution rate as compared to the pure drug. The spectroscopic study revealed that the NFs convert the crystalline irbesartan into amorphous form and due to this; the dissolution and solubility of irbesartan were enhanced. Consequently, these could be beneficial for oral thin film formulation development^[118].

Antipyretic loaded NFs:

Since from ancient times, the various traditional treatment has been used to control fever^[119]. Various literature reports the delivery of antipyretic agents to the management of life-threatening health issues worldwide. The epoxy-coated spinneret was fascinated by the narrower size distribution of electrospun NFs of CA and model drug acetaminophen as compared to the stainless steel spinnerets. Interestingly, the working solution of polymeric and drug blend and epoxy coated spinneret showed weaker interfacial tension. Additionally, the physical state of acetaminophen converts from a crystalline into the amorphous form. Additionally, this epoxy coated spinnerets based NFs showed the sustained release of acetaminophen. Accordingly, it could be potentially utilized in quality NFs progress^[120].

Hormones loaded NFs:

Steroidal hormone namely, progesterone has a major account for the management of pregnancy especially in the animal it utilized as a suppressing agent for estrus and ovulation. Furthermore, it provides the synchronization of estrus and ovulation process in for farm animals. Herein the delivery of progesterone by controlled matter was achieved by using zein. Owing to the exceptional property of zein like biocompatible and biodegradable, high elasticity, low hydrophilicity, and film-forming ability, overcome the drawbacks of non-degradable polymers. Herein, the offers the plasticity for an NFs and showed the sustainability of progesterone. Consequently, the progesterone-loaded NFs could be more potentially used for estrus synchronization of bovines in livestock animals for controlled delivery of progesterone^[121]. Vlachou and coauthors prepared for the melatonin (MLT) loaded CA/PVP/HPMC (hypromellose) in the delayed-release capsules. The PVP and HPMC NFs and CA/PVP NFs showed 30 min and 120 min showed 30 min release in gastric fluid respectively. Such type of rapid, delayed, immediate, or modified release NFs could potentially use in the sleep-disturbing treatment^[122].

Anti-diabetic agent loaded NFs:

As per the World Health Organization (WHO), Diabetes mellitus is a chronic metabolic disorder^[123]. A list of chemical/ synthetic agents and natural phytoconstituents is available to the management of diabetes. Recently, the authors prepared the quercetin-loaded zein NFs for diabetic patients in case of nerve damage recovery. In that, the NFs showed the excellent loading capacity and converted the crystalline quercetin to non-crystalline form, and maybe the interaction between zein polymer and quercetin. These NFs subjected to the treatment of diabetes-induced rats for neuropathy. As a result, it was observed that the quercetin loaded zein NFs increased the recovery from neuropathy and increased the oxidative stress level as well as pERK/ERK ratio expression in the nerve lesion^[124].

Probiotics delivery by NFs:

Human microbiota imbalance is a recent new issue in human health and due to that, probiotics take noteworthy attention for the treatment of dysbiosis. To date, there is no article available for Probiotics delivery via electrospun NFs. Skrlec and co-authors established the Lactobacillus plantarum (L. plantarum ATCC 8014)-loaded monolithic PEO and composite PEO/ cryoprotectant spun NFs for local delivery like the vagina. Principally, the lyoprotectant promotes the viability and it does not show much effect on NFs morphology. Consequently, these prepared NFs provide the local delivery of probiotics with high loading and excellent shelf life. Thus, it could be more useful to the delivery of lactobacillus species in vaginal drug delivery ^[125].

CONCLUSION:

Electrospinning nanofibers are an old technology for the manufacturing of nanofibers with a comparatively simple outline. However, in recent years it concerned great consideration because of its potential in biomedical and other nanotechnical applications. It offers several types that tune the NFs for novel drug delivery, because of its large surface-volume ratio also cost-effectiveness are smart features. The parameter optimization provides the stupendous result for NFs morphology and functions. In this review, all summarized pharmaceutical applications revealed the utilization of such advanced technology for providing the stability, biocompatibility for active and besides, improve the dissolution, solubility, and bioavailability of active. Also, the development and modification of NFs fabrication provide the high drug loading ability, modified/pH-dependent release, targeted drug delivery, and further it avoids the burst release. Furthermore, owing to the promotion of cell adhesion, migration, and proliferation, NFs takes major attention in wound healing and dressing. Even if, the use of spun NFs is resourceful in pharmaceuticals, but there is a demand for progression and research for the appropriate utilization of electrospun NFs in pharmaceutical applications. Finally, it concludes that the spun NFs had revealed effective in a great diversity of biomedical applications. For extensive accessibility of NFs based dosage form to in the pharmaceutical application, the ES NFs based novel drug delivery scaling up is a must.

Table 4: Summary table of pharmaceutical application of electrospun nanofibers

Sr. No.	Polymers	Drug/ Protein/Enzyme	Application	Reference
1.	PLA	Metronidazole	Antibiotic	[48]
2.	PLGA	Cefoxitin Sodium	Antibiotic	[49]
3.	EL100	Fluconazole	Antibiotic	[50]
4.	PLGA	Vancomycin	Antibiotic	[51]
5.	Alginate-PEO	CF	Antibiotic	[51]
6.	PCL	Levofloxacin & Irgasan	Antibiotic	[53]
7.	PVA	2% CHX	Antibacterial	[54]
8.	PCNU	CF	Antibiotic	[55]
9.	CS-PEO	Microalgal phenolic compound	Antibacterial	[56]
10.	β-CD	Silver sulfadiazine	Antibiotic	[57]
11.	PLGA	Salinomycin	Antibiotic	[58]
12.	PCL	Emblica officinalis	Antibacterial	[59]
13.	PVA/CS	Bidens pilosa leaves extract	Antibacterial	[60]
14.	PCL	AP	Antibacterial	[44]
15.	PCL	siRNA	Anticancer	[63]
16.	PLA-PEG-PLA	Tamoxifen	Anticancer	[64]
17.	MWCNTs/PLGA	DOX	Anticancer	[65]
18.	PLA/pearl	DOX	Anticancer	[66]
19.	PLLA	5-FU & Gemcitabine	Anticancer	[67]
20.	SF	Curcumin & DOX	Anticancer	[68]
21.	PLA and CS	Paclitaxel	Anticancer	[69]
22.	GL-PLA	Curcumin	Anticancer	[70]
23.	CS/PVA	DOX	Anticancer	[71]
24.	PLLA	Titanocene dichloride	Anticancer	[72]
25.	PVA	Ketoprofen	NSAIDs	[74]
26.	PVA	Meloxicam	NSAIDs	[75]
27.	PLGA/GL	Fenbufen	NSAIDs	[76]
28.	DMTU-PEG-d, l-lactide	Paracetamol	NSAIDs	[77]
29.	ES-ERS	Indomethacin	NSAIDs	[78]
30.	PDLG	Diclofenac sodium	NSAIDs	[79]
31.	PLLA	Diacerein	Anti-inflammatory	[80]
32.	GL	Piperine	Anti-inflammatory	[81]
33.	PVP-dextran	Ibuprofen, Aspirin	NSAIDs	[82]
34.	CA	Tetracycline HCl	Wound dressing	[83]
35.	CA	RosA	Anti-inflammatory	[84]
36.	PLA	Diclofenac	NSAIDs	[85]
37.	PCLEEP	NGF	Protein delivery	[86]
38.	PVA	BVA	Protein delivery	[87]
39.	PVA	Capsaicin	Analgesic	[88]
40.	Sodium alginate/PEO	Lidocaine	Analgesic	[89]
41.	PEO/SA-T	Acetaminophen	Analgesic	[90]
42.	SF	Vitamin C	Antioxidant	[96]
43.	PVA-PVAc	CF HCl	Antibiotic	[99]
44.	CS–EDTA-PVA	Lysozyme	Enzyme	[100]
45.	PVA	AgNPs	Antibacterial	[101]
46.	POCA	Polypropylene fumarate	anti-inflammatory	[102]
47.	PVA -CS	Tetracycline HCl	Antibiotic	[103]
48.	PVP	THC	anti-oxidant & anti-inflammatory	[104]
49.	PCL	Tridax Procumbens	Antibacterial	[105]
50.	SF	Hydroxytyrosol	Antimicrobial	[106]
51.	CS-PEO/Fb	PDGF	Wound dressing	[107]
52.	CMC-PEG	Diclofenac	Wound healing	[108]
53.	PCL	CF HCl and quercetin	Wound healing	[109]
54.	PLA-PEO	GSE	Wound dressing	[110]
55.	PVA	Luciferase	Enzyme	[87]
56.	PVA	Ampicillin	Antibiotic	[111]
57.	Eudragit and PVP	Mebeverine HCl	Antispasmodic	[112]
58.	PCL-PEG	Dipyridamole	Anticoagulant	[114]
59.	PVP K90	Irbesartan	antihypertensive	[118]
60.	CA	Acetaminophen	Antipyretic	[120]
61.	Zein	Progesterone	Steroidal Hormones	[121]
62.	CA/PVP/HPMC	Melatonin	Chronobiotic Hormone	[122]
63.	Zein	Quercetin	Antidiabetic	[124]
64.	PEO/ Lyoprotectant	Lactobacillus plantarum	Probiotics	[125]

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

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Received on 16.03.2020 Modified on 21.04.2020

Accepted on 10.05.2020      ©Asian Pharma Press All Right Reserved

Asian J. Pharm. Tech.  2020; 10(3):187-201.

DOI: 10.5958/2231-5713.2020.00032.X