Transdermal drug delivery using electrospun membrane

Electrospinning has been used to fabricate dermal patch for wound healing and drug delivery. Electrospun dermal patch exhibits several advantages such as high porosity, high surface area and exceptional flexibility. For practical application as dermal patch, its flexibility allows it to maintain close proximity to the contours of the skin surface. A study by Ghosal et al (2018) showed using polycaprolactone (PCL) that the resultant electrospun membrane exhibited improved flexibility over cast film without compromising durability. Such enhancement in plasticity has been attributed to the amorphous state of the electrospun fibers while the same polymer solution in cast film form contains semi-crystalline domain which made it brittle and inflexible.

Transdermal drug delivery can be easily achieved by incorporating drugs into the electrospun dermal patch. Anti-inflammatory drugs, pain-relief drugs and herbal extracts such as chilli herbal extract or capsaicum extract [Tanadchangsaeng N et al 2016] has been successfully electrospun with carrier polymers for use as dermal patch. Ngawhirunpat et al (2009) used electrospun polyvinyl alcohol (PVA) fibers for encapsulation of meloxicam. High porosity and surface area of PVA fibers meant that the release of meloxicam is faster than as-cast PVA films. Drug release rate from PVA fibers may also be modified by the addition of water soluble polyvinyl pyrrolidone (PVP). Drug loaded in electrospun fibers may also be maintained in an amorphous state which will facilitate diffusion and adsorption through the skin. Shi et al (2013) showed that ibuprofen (IBU)-loaded in cellulose acetate/poly(vinyl pyrrolidone) (CA/PVP) blends was uniformly distributed in an amorphous state. IBU diffusion and ex vivo skin permeation was also found to be faster in electrospun nanofibers membrane compared to cast membrane. Kalantary et al (2020) tested the effectiveness of electrospun vitamin E-loaded hybrid poly(ε-caprolactone) (PCL)/gelatin (Gt) nanofibres mats for protection of the skin from reactive oxygen species (ROS) formation. The electrospun PCL/Gt mat showed a fast initial degradation rate as shown by 43% weight loss on day 7 and 50% weight loss on day 14 in PBS solution. This is probably due to faster degradation rate of gelatin as compared to PCL. The study also showed that there is an initial burst release of vitamin E from the fibers with 69% and 80% released at 12 hours from 1 and 5% loading respectively. The protection offered by vitamin E was demonstrated by testing with tert-Butyl hydroperoxide (t-BHP) induced oxidative stress on human dermal fibroblast cells (HDFCs). The viability of HDFCs was significantly higher with PCL/Gt nanofibres mats loaded with vitamin E compared to mat without. The antioxidant Vitamin E contains a hydroxyl group on a chromanol ring which readily donates a proton to reduce free radicals. Thus the high surface area of electrospun vitamin E-loaded hybrid PCL/Gt nanofibres mats has the potential to protect the skin from oxidative stress by reducing free radicals.

Drug release of a dermal patch may also be varied using a hybrid of electrospun fibers and other matrices. Sa'adon et al (2021) constructed a dual layer polyvinyl alcohol (PVA) dermal patch made of an electrospun layer and a cryogelation (freeze-thaw) layer. Diclofenac sodium (DS) was used as the model drug and was loaded into the cryogelated PVA layer while the electrospun layer was used to control the release rate of DS from the cryogelated matrix. Construction of the dual layer involves electrospinning the nanofiber layer followed by spreading of aqueous PVA solutions over the membrane for the freeze-thawing process. With a thicker electrospun PVA layer, the release rate of DS is lower. A thicker electrospun PVA layer was also found to have lower swelling capacity and a greater drop in swelling capacity over a 24 h period. With the DS-medicated dual layer PVA patch at 2% w/v drug loading, the controlled drug release due to the presence of the electrospun layer may enable continuous drug release up to 24 h.

In wound healing application, highly porous electrospun dermal patch allow movement of air to the wound surface while the small pore size prevents bacteria from reaching it. Kaur et al (2015) showed that higher amount of PVP in the PVP/PVA composite will increase antiemetic GH (Granisetron hydrochloride) drug release and permeation across skin. This drug and its application through a dermal patch will be able to relieve the side effects like nausea and vomiting for cancer patients.

In vitro drug release of the electrospun nonwoven nanomats of PRX and PCL-PVAc-PEG graft copolymer (1:13 w/w ratio) in purified water (purple square), pH 7.2 phosphate buffer (green triangle), and pH 1.2 buffer solution (blue diamond) at 37 °C (n = 5). [Paaver et al. BioMed Research International, vol. 2014, Article ID 789765, 7 pages, 2014. doi: 10.1155/2014/789765. This work is licensed under a Creative Commons Attribution 3.0 Unported License.]

Skin surface is typically acidic and the drug release profile needs to be checked at low pH. Paaver et al (2014) incorporated piroxicam (PRX) into electrospun Soluplus (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PCL-PVAc-PEG)) fibers for wound therapy. The drug release profile of Soluplus fibers was found to be dependent on the pH. Although pH of skin at its natural state is below 5, it does vary considerably when other cosmetic products, soap or tap water are used [Lambers et al 2006]. This may impact the drug release profile of the electrospun fibers and this must be taken into consideration.

Misra et al (2017) tested the effect of tolnaftate-loaded polyacrylate electrospun nanofibers on dermatophytosis. They used a combination of Eudragit grades (ERL100 and ERS100) to construct an electrospun membrane with good exudate absorption ability, adhesion property on wound and controlled release of tolnaftate. PEG 400, a plasticizer was added to the mixture to reduce agglomeration of tolnaftate. With 3:1 ratio of ERL100/ERS100, the preferred sustained drug release for 8 hrs were obtained. An in vivo rat model was used to test the effectiveness of the tolnaftate loaded electrospun fibers on Trichophyton rubrum and M. canis. While the drug loaded membrane was shown to be effective against T. rubrum, it was not effective against M. canis. Interestingly, mice treated with pure tolnaftate had symptoms of dermatophytosis after seven days but the drug loaded membrane were able to completely eradicate T. rubrum. Better efficacy of the membrane can be attributed to the continuous drug release over the treatment period. Depending on the treatment requirements, the drug release rate and profile of the loaded electrospun membrane needs to be considered. It is sometimes possible to make small changes to the release rate by altering the electrospun fiber topography without changing the drugs and polymer. Saadatmand et al (2019) tested the effect of textured electrospun membrane on the release rate of cetirizine in Nylon 6 fibers. Electrospun Nylon 6 fibers were deposited on smooth surface substrate, pentagonal grids and tetragonal grids. From their study, they found that drug release from membrane with pentagonal profiling has the fastest release rate and followed a first order release model where the release rate is concentration dependent. Both smooth surface and tetragonal profile membrane followed a Higuchi model where the release rate is slower.