Drug-loaded electrospun fibers delivery channel

Electrospun fibers have been investigated for drug delivery due to the diversity of materials that can be used and the range of incorporation methods available. Conventional methods of drug delivery are through systemic administration such as oral means or injection. This often requires higher dosage and comes with more side effects. Targeted and local drug delivery is preferred as it results in less co-lateral damages and is usually more effective. Electrospun fibrous materials can be used for this purpose given its structural integrity prior to delivery. Routes of delivering the electrospun material to the treatment sites include oral, implantation, transdermal and transmucosal.

Oral Delivery

In oral delivery, high surface area of electrospun fibrous membrane enables rapid dissolution and release of its payload. This works by placing the thin membrane on the tongue where its moisture and saliva dissolves the membrane and releases the drug. Water-soluble materials are often used in this application and have been shown to completely dissolve within 4s while maintaining sufficient mechanical integrity for handling [Dott et al 2013]. Rapid release of the drug in the mouth is necessary where the targeted treatment site is in the oral cavity. Delays in the drug release will result in most of the drugs been ingested which will result in less optimal treatment. Implant to treatment site

Implant to treatment site

For treatment of diseased organs, electrospun membrane loaded with drug can be implanted close to the treatment site for sustained and localized release. This has been successfully tested in the treatment of cancerous tumor. In an in vivo study, dichloroacetate released from electrospun polylactide mats covering solid tumor showed 89% necrosis of the tumor compared to only 51% for oral administration of dichloroacetate [Liu et al 2012]. For some drugs, prolong exposure to the surrounding liquid may cause it to lose its effectiveness. Having the drug loaded in a matrix reduces the exposure and maintains its effectiveness until it is released. Electrospun membrane has also been tested for treatment in highly sensitive area such as the central nervous system (CNS). Disruption of the blood-brain barrier for local drug delivery may result in severe inflammatory reactions. Rafalowska et al (2014) used electrospun poly(L-lactide-co-caprolactone) membrane for sustained drug delivery to the CNS by implantation of the nanofiber mat pieces into rat spinal cords. They found that three weeks after implantation, there were no inflammation which makes electrospun membrane a suitable material for this purpose.

Dermal Patch

Electrospinning has been used to fabricate dermal patch for wound healing. Highly porous electrospun dermal patch allow movement of air to the wound surface while the small pore size prevents bacteria from reaching it. Transdermal drug delivery can be easily achieved by incorporating drugs into the electrospun 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). Kaur et al (2014) 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.

Vaginal Mucosa

Innovative construction and application of electrospun membrane has seen its delivery of drug via transmucosal means. Targeted application for this is the prevention of sexually transmitted infections through delivery of drugs to the vaginal mucosa. The membrane may function solely as a drug delivery agent or a combination of drug delivery and physical barrier to sperm penetration. Ball et al (2012) fabricated an electrospun hydrophilic polyethylene oxide (PEO) and hydrophobic poly-L-lactic acid (PLLA) fibers to form a mesh that took the shape of a hollow tube. Several compounds such as maraviroc, 3'-azido-3'-deoxythymidine and acyclovir have been incorporated into the fibers to demonstrate its versatility. The mesh was demonstrated to physically block sperm penetration and show viral inhibition from the loaded drugs [Ball et al 2012]. Another study aims to use the electrospun fibers for rapid delivery of anti-HIV microbicides. For this application water soluble PVP or polyethylene oxide (PEO) were being electrospun to form fibers loaded with maraviroc. The resultant membrane was able to release the drugs in less than 6 minutes which is much faster than other solid dosage forms like films and tablets [Ball et al 2014].

Fiber meshes are a physical and chemical barrier against sperm. (a) Motility of human swim-out sperm was completely inhibited within 5 min for 0.05 and 0.5% glycerol monolaurate (GML). Data show counts of motile and immotile sperm at 2 min (gray line) and 5 min (black line). Baseline sperm motility (~89%) was measured at the beginning and end of experiment using a PBS control (dotted line). (b) Sperm viability is reduced in whole semen incubated with GML compared with media control. (c) GML release from fiber meshes was qualitatively measured using TLC. (d, e) A transwell assay was used to test the physical barrier properties of the fiber meshes by replacing Millicell cell culture insert membranes (3 ?m pore diameter) with a blank fiber mesh (n = 3). (f, g) SEM micrographs of the upper (f) and lower (g) side of Millicell control membrane. (h, i) SEM micrographs of upper (h) and lower side (i) of fiber mesh show that no sperm penetrate through the fiber mesh. [Ball et al PLoS ONE 2012; 7: e49792. doi:10.1371/journal.pone.0049792. This work is licensed under a Creative Commons Attribution 4.0 International.]

Via a Cannula

A thin electrospun membrane may be injected into the treatment site using a cannula. Garkal et al (2022) demonstrated the use of thin lutein-loaded electrospun polycaprolactone (PCL) membrane for injection into the eye for treatment of age-related macular degeneration. Lutein was first blended into PCL solution and electrospun to form a thin membrane. Garkal et al (2022) showed that the thin membrane rolled into a tube may be inserted into a 21 Gauge needle from the back and ejected through the tip using a suitable thin wire to push the membrane through. Using a rat model, the membrane was successfully injected into the vitreous of the rat using the needle.

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