Abstract
Purpose:
Common topical formulations, such as eye drops or ointments, suffer from low ocular bioavailability due to rapid drainage through the naso-lacrimal duct, nearly constant dilution by tear turnover, and low drug permeability across the corneal epithelium. As a result, topical formulations are normally administered multiple times daily in order to achieve therapeutic efficacy, resulting in a higher potential for side effects and lower patient compliance. Our study aims to design nano-scaled drug carriers to overcome the rapid clearance of current eye drop solutions thereby improving drug retention on the corneal surface.
Methods:
NPs composed of poly(D,L-lactide)-b-Dextran (PLA-Dex) surface functionalized with a mucoadhesive ligand, phenylboronic acid (PBA), were developed as drug carriers. Using Cyclosporine A (CycA) as a model drug, CycA molecules were encapsulated within PLA-Dex using emulsification. Controlled drug release and biocompatibility studies were performed in vitro and in vivo.
Results:
We showed that the nanoparticle carrier can be used to release CycA in vitro and in vivo. The average size of NPs were found to be in the range of 25 and 28 nm. The NPs showed encapsulated up to 13.7 wt% CycA and exhibited sustained release for up to 5 days in vitro at a clinically relevant dose. We fine-tuned the PBA density on the NP surface to maximize the mucin-NP interaction without compromising the particle stability in vitro. We showed that the NP formulation did not significantly affect the transparency or the solution viscosity, which improves patient compliance. The surfaces of the nanoparticles have a defined number of ligands capable of targeting the corneal surface, allowing drugs encapsulated in the particles to effectively circumvent the tear turnover mechanism, and significantly improving their corneal retention.
Conclusions:
The surface of the nanoparticle formed from a linear block copolymer poly(D,L-lactide)-b-Dextran was modified with PBA to form a mucoadhesive nanoparticle for topical ocular drug delivery application. The simplicity of NP design suggests it can deliver a wide range of bioactive agents including both hydrophilic and hydrophobic compounds. These results suggest the potential of our nanoparticle approach can be used as a platform technology to provide long-lasting delivery of therapeutic agents to treat anterior eye diseases.
Keywords: 608 nanomedicine •
482 cornea: epithelium •
557 inflammation