Nanospheres for Ophthalmic Drug Delivery

Abstract

Abstract: : Purpose: Various ophthalmic drugs were encapsulated within carbohydrate–based, biodegradable nanospheres to assess their potential for enhanced drug delivery. The structure of the nanospheres and their ability to be functionalized can be utilized for controlled release of encapsulated drugs at the target site. Characterization of drug binding and permeability will allow for modifications of the nanosphere system for enhancement and optimization of ophthalmic drug delivery. Methods: Diclofenac and ciprofloxacin were each encapsulated by self assembly of pullulan–b–polycaprolactone to form stable linear block core–shell nanospheres. Two epithelial cell lines (ZR–75–1 human mammary epithelial cells, which express MUC–1 and MUC–2 mRNA, and MDCK cells, which do not) were grown to confluence on Millicell^TM membrane inserts. Nanosphere–encapsulated and free drug permeability were assessed at various timepoints using UV spectroscopy and compared to drug passage through blank Millicells. Rhodamine–labeled nanospheres were used to determine transport of the nanospheres across the cell barrier. Results: The rate of transport of nanosphere–encapsulated vs. free diclofenac through the ZR–75–1 cells over a 60 minute period was comparable, but was less than the rate of drug diffusion through blank Millicells. A similar result was found for nanosphere–encapsulated and free ciprofloxacin. Neither free rhodamine or rhodamine–labeled nanospheres crossed the tight junctions of the MDCK cells. In the ZR–75–1 cells it was observed that rhodamine–labeled nanospheres passed through the cell monolayer. These results suggest that the nanospheres are actively transported across the epithelial barrier of this cell line, possibly due to the presence of carbohydrate binding sites such as MUC–1 and MUC–2. Conclusions: This nanosphere system provides the potential for a stable, biodegradable, non–toxic drug delivery system, which will allow for sustained and controlled release of target drugs. It is adaptable for specific indications and various drug molecular structures.

Keywords: pharmacology