Design and development of Dasatinib nanoemulsions for ocular delivery: In vitro characterization, biocompatibility, and Ex vivo ocular irritation study

Abstract

Dasatinib, a potent tyrosine kinase inhibitor with dual anti-inflammatory and anti-angiogenic properties, holds significant potential for treating ocular diseases such as Corneal Neovascularization (CNV), uveitis, and diabetic retinopathy. However, its low aqueous solubility and limited ocular retention present major formulation challenges. This study concentrated on the design and evaluation of Dasatinib nanoemulsions (Dasa NEs) for ocular delivery, utilizing nanotechnology to enhance solubility, stability, and therapeutic efficacy. The Dasa NEs were prepared using Oleic acid (lipid phase), Tween 80, Propylene Glycol (PG) (Smix), with component ratios optimized through pseudo-ternary phase diagrams. The resulting formulations exhibited nanoscale droplet sizes (<100 nm), low polydispersity indices, and stable zeta potential, ensuring colloidal stability and efficient delivery. Comprehensive physicochemical evaluations confirmed that the NEs possessed ideal pH, refractive index, surface tension, and viscosity for ophthalmic applications. Biocompatibility assessments using the MTT assay on SIRC cells demonstrated high cell viability, while HET-CAM tests confirmed the absence of significant ocular irritation. In vitro diffusion studies indicated improved drug permeation, highlighting the potential for prolonged therapeutic effects. Stability studies further validated the robustness of the formulations under various conditions. The developed nanoemulsions offer a promising, non-invasive platform for ocular drug delivery, improving patient compliance and therapeutic outcomes. Future studies should focus on in vivo evaluations and long-term safety to advance the clinical translation of this novel formulation.