ABSTRACT
One example of electrospun fibers for drug delivery is a coaxial nanofiber solid dispersion of acyclovir for oral delivery developed by Yu et al. [17]. Acyclovir is a hydrophilic low molecular weight (MW) drug often used to treat herpes simplex virus (HSV). Despite being hydrophilic, acyclovir has poor aqueous solubility in phosphate buffered saline (PBS) (around 12 µg/mL), leading to low bioavailability [18]. Repeated dosing to establish effective drug levels can result in high levels of side effects, such as nausea or gastrointestinal problems. Yu et al. [17] developed hydrophilic polyvinylpyrrolidone (PVP) fibers containing sucralose as a sweetener, sodium dodecyl sulfate (SDS) as a transmembrane penetration enhancer, and acyclovir. They prepared fibers using coaxial electrospinning, a method by which two solutions (a core solution and a sheath solution) may be simultaneously incorporated into fibers in a concentric fashion. This electrospinning technology allows for simultaneous loading of multiple components with different physicochemical properties into a single dosage form, as well as customization of fiber surface properties or structural properties. For example, Yu et al. employed different solvents in the fiber core and sheath solutions to ensure the molecular dispersion and solubility of the included compounds. The core of the fibers, spun from a mixture of ethanol and dimethylacetamide, contained approximately 20% (w/w) acyclovir molecularly dispersed in PVP. Meanwhile, the sheath of the fibers, spun from a mixture of water and ethanol, contained the highly water soluble compound sucralose and the permeabilizing agent SDS. Yu et al. found that these coaxial PVP nanofibers readily dispersed acyclovir, sucralose, and SDS such that no crystalline compounds were present in the
final materials. By making acyclovir amorphous, Yu et al. removed the thermodynamic barrier of overcoming crystal lattice energy before the drug could enter solution (significant, as acyclovir has a melting point well above 200°C [19]). As a result of the fiber’s hydrophilicity, high surface-area-to-volume ratio, solid dispersion of acyclovir and inclusion of SDS, the coaxial nanofiber formulation released 100% of the formulated acyclovir in 1 min (compared to 50% dissolution of pure acyclovir particles in 60 min) and increased the rate of porcine sublingual mucosa penetration over sixfold [17]. Similar results might be expected for delivery to the female reproductive tract or the rectum if such technology (containing multiple ARV agents rather than SDS and sucralose) were developed for pericoital anti-HIV microbicides.Release of multiple agents from single dosage forms may help improve user adherence to microbicide use. If a single product is capable of anti-HIV activity in addition to contraception, or additional sexually transmitted infection (STI) prevention, then women may be more likely to use it based on their perceived risk for indications other than HIV. In addition, combined delivery of ARV compounds for use in microbicide products has the potential for decreasing required doses needed for protection, thus reducing side effects, while reducing the risk of acquiring drug-resistant HIV strains [4,6,20]. Coaxial electrospinning and another technique known as emulsion electrospinning are two examples of recently developed techniques that allow for increased control over the design and deployment of fibers for such drug delivery applications. As seen above, coaxial fibers can facilitate the co-formulation of small molecules with different physicochemical properties. Coaxial fibers also allow engineers to alter the release rate of core-encapsulated compounds or to electrospin materials that may otherwise not have the required physical properties to form uniform fibers [21]. In emulsion electrospinning, an oil or aqueous phase that is not amenable to fiber formation may be emulsified in an aqueous or oil polymer solution, respectively, and electrospun to create beaded strands or even regular fibers with continuous core and shell regions [22]. These two techniques expand the range of creative solutions that can be developed for drug delivery from electrospun materials.
