Eye drops are widely used for the noninvasive self-administration of drugs to treat ocular disorders. However, most eye drop preparations are rapidly eliminated within minutes due to intraocular turnover such as blinking and tear fluid, significantly limiting drug bioavailability. To maintain an effective therapeutic concentration, frequent administration is required, which negatively impacts patient compliance and treatment outcomes. In particular, achieving retinal drug delivery via eye drops remains a major challenge, as drugs must penetrate multiple biological barriers from the conjunctival sac, including the cornea and conjunctiva. Thus, there are few preparations demonstrated to achieve retinal drug delivery via eye drops. An additional challenge to ocular drug delivery via eye drops is that while the most common eye drops are water-based, many drugs exhibit poor water solubility. To enhance drug permeability and solubility, encapsulation in drug nanocarriers such as liposomes is a promising strategy. However, nanocarriers also have inherent limitations, including restricted drug-loading capacity and an inability to prevent intraocular turnover. Additionally, because ophthalmic suspensions have been reported to induce impaired vision after administration, suspensions may have similar effects, causing blurred vision and reducing patient comfort.
In the current study, we explored the potential of biodegradable nanofiber mats fabricated from polymers via electrospinning (ES) as a topical ocular formulation. Electrospinning employs a high voltage to generate nanofibers with diameters ranging from tens to hundreds of nanometers. The high surface area, porosity, and mechanical strength of these nanofibers confer substantial loading capacity and highly tunable release kinetic for drugs incorporated during ES. These nanofiber mats also allow for noninvasive self-administration by direct application to the conjunctiva, providing sustained drug release over several hours. By circumventing the key limitations of eye drops, nanofiber-based delivery systems may improve patient compliance and eliminate the need for frequent professional intervention. Moreover, ES of polymers can be achieved at room temperature, making it suitable for heat-sensitive biopharmaceuticals. Nanofibers can enhance the solubility of poorly water-soluble drugs through solid dispersion. These mats also exhibit superior stability for long-term storage as the amorphous state was sustained under moisture-free conditions. Although conjunctival application may cause foreign body sensation, this issue can be mitigated by administering the mats before bedtime, allowing them to dissolve and degrade during sleep.
In this study, Polyvinyl alcohol, a hydrophilic and biodegradable polymer widely used in pharmaceuticals, was employed as the nanofiber excipient due to its well characterized gelling behavior on the corneal surface as well as highly tunable physicochemical properties depending on the degree of polymerization and hydrolysis. C6 was incorporated into nanofibers via emulsion electrospinning and maintained in an amorphous state within the fibers to enhance solubility. Nanofibers were prepared using PVA with different polymerization and hydrolysis degrees. The corneal epithelial cell damage potential was examined in monolayer culture by electrical resistance measures. All preparations demonstrated good biocompatibility without corneal epithelial cell barrier damage. The C6 release profiles varied depending on polymerization and hydrolysis degrees of PVA, indicating tunable release capacity. Low-polymerization PVA resulted in rapid C6 release, whereas completely hydrolyzed PVA enabled sustained release. Administration of C6-containing nanofiber mats resulted in 5- to 18-fold higher retinal concentrations at 6 h compared to emulsion groups. This PVA nanofiber-based system can safely prolong ocular drug delivery and improve bioavailability for poorly water-soluble compounds.
Article information
Journal：International Journal of Pharmaceutics
Journal title：Instant-gelling electrospun polyvinyl alcohol nanofiber mats for enhanced retinal drug delivery via topical ocular application
Authors：Takaaki Ito, Shomu Uda, Yudai Taie, Yuiko Kamiya, Eriko Yamazoe, Kouji Hara, Kohei Tahara
DOI： 10.1016/j.ijpharm.2025.126128
Lab: Laboratory of Pharmaceutical Engineering (https://gpu-seizai.jp/)