A grafted copolymer-based nanomicelles for topical ocular delivery of everolimus: Formulation, characterization, ex-vivo permeation, in-vitro ocular toxicity, and stability study

Treatment of posterior uveitis via topical route is desirable but cannot be achieved by conventional drug delivery strategies. Therefore, the aim of this study is to develop a topical nanomicellar formulation of an immunosuppressant drug, everolimus using Soluplus®, a grafted copolymer of polyvinyl caprolactam-polyvinylalcohol-polyethyleneglycol (PVCL-PVA-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.

Highlights

Soluplus (a grafted copolymer) mediated nano-micelles as an appropriate nanocarrier for hydrophobic drugs across the eye.

Evr-NMs, a potential nanocarrier for topical ocular drug delivery for uveitis.

Evr-NMs remain in the circulatory system for longer duration and get accumulated in the inflammatory area.

Evr-NMs enhanced the permeation of the drug through the cornea via topical route.

Soluplus-everolimus nano micelles were found to have a low CMC (7.2 µg/ml) and 65.55 nm 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 everolimus suspension. The everolimus nanomicelles showed significantly higher permeation across goat cornea than everolimus suspension (p<0.001).

CLSM of prepared nanomicelles confirmed the deeper permeation through the goat cornea. These results indicated the significantly higher accessibility and improved drug bioavailability thus, everolimus nanomicelles could be considered a promising topical drug delivery nanocarrier for treating uveitis.

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Article Information: Nikita., Mohd. Aqil, Yasmin Sultana. European Journal of Pharmaceutical Sciences, Volume 159, 2021. https://doi.org/10.1016/j.ejps.2021.105735.