Development and Characterization of Exosomes Mediated Transdermal Gel for Enhanced Delivery of Hydroxyurea

Purpose: The present study was focused on formulation and characterization of a biocompatible transdermal gel using human plasma-derived exosomes as a carrier system for the localized and sustained delivery of hydroxyurea in breast cancer. Method: Exosomes were successfully isolated from human plasma using a combination of differential centrifugation and ultrafiltration techniques. Hydroxyurea was loaded into the exosomes via a freeze–thaw cycle. In this study, the exosomes mediated hydroxyurea was incorporated into carbopol gel at varying concentrations of G1 = 0.5%, G2 = 1%, G3 = 1.5% and G4 = 2% and characterized by viscosity, spreadability, drug content, in vitro drug release, skin permeability and biocompatibility studies using HEK-293 cells and MTT assay on MCF-7 cells. Results: The exosomal hydrxyurea gel (G4) demonstrated optimal properties, including skin-compatible pH, consistent drug loading, suitable viscosity, and excellent spreadability. All formulations exhibited < 10% hemolysis, confirming superior hemocompatibility. Exosomes mediated hydroxyurea gel achieved 8.81-fold higher skin permeability versus hydroxyurea solution and substantially more than the hydroxyurea gel, with 1.8-fold greater cytotoxicity against MCF-7 cells. Conclusion: This exosomes mediated transdermal drug delivery system enables sustained, localized drug release, improving therapeutic efficacy, minimizing adverse effects, stabilizing exosomes, and prolonging tumor-site retention.