Design Characterization and Evaluation of Ocular Nanoformulation

Abstract

newlineTreatment of posterior uveitis via topical route is desirable but cannot be achieved by conventional drug delivery strategies. Therefore, this study aims to develop a topical nanomicellar formulation of an immunosuppressant drug, everolimus using Soluplus®, a grafted copolymer of polyvinyl caprolactam-polyvinylalcohol-polyethyleneglycol (PVCLPVA-PEG) for improved permeation through ocular epithelia with minimal or no irritation resulting in enhanced ocular bioavailability at the posterior segments of the eye for the treatment of uveitis. Soluplus-everolimus nano micelles were found to have a low CMC (7.2µg/ml) and 65.55nm in size. The prepared nanomicelles were characterized for surface morphology by TEM, SEM, and AFM and found to have spherical particles with a smooth surface. The nanomicelles were found to have high encapsulation efficiency and result in sustained release of everolimus when compared with its suspension. The everolimus nanomicelles showed significantly higher permeation across goat cornea than suspension (plt0.001). CLSM of prepared nanomicelles confirmed the deeper permeation through the goat cornea. Also, the EVR-NMs were found to be stable for 3 months at a temperature of 4ºC when stored under dark conditions. The in-vitro ocular irritancy potential was determined using HET-CAM assay and the results showed that the EVR-NMs did not result in ocular irritancy and hence was safe for ocular use. The MTT assay for EVR-NMs was performed using rabbit corneal epithelial (SIRC) cell line and % cell viability was evaluated and results showed that EVR-NMs were safe and did not result in any significant cytotoxicity to rabbit corneal epithelial cells. The pharmacokinetic studies for EVR-NMs were also performed and it was found that bioavailability of the everolimus was significantly enhanced at the posterior segment of the eye and hence, site-specific drug delivery can be obtained by the prepared nanomicelles. The uveitis was induced in Wistar rats and was treated by topical administration...