Development of Degradable Silylated Castor Oil-Based Microparticles for the Sustained Release of a Lipophilic Anti-Cancer Drug

Background/Objectives: Hybrid microparticles (HMP) based on silylated vegetable oils have recently emerged as promising carriers for the sustained delivery of poorly water-soluble drugs, offering a controlled release without a burst effect and excellent biocompatibility. However, their limited degradability and the acidic conditions required for the sol–gel encapsulation process restrict their biomedical applicability, particularly for acid-sensitive active compounds. The aim of the present study was to develop new degradable vegetable oil-based HMP with improved drug-solubilization capacity while preserving compatibility with acid-sensitive molecules through an adapted mild sol–gel process, buffered with sodium citrate. Methods: Two new modified oils were synthesized from castor oil derivatives, including a monoglyceride (glyceryl monoricinoleate) and a polylactic acid (PLA) conjugate, to enhance both solubilization capacity and degradability. The acid-sensitive, lipophilic antitumor compound JMV5038 was used as a model drug. Modified oils were evaluated for drug-solubilization capacity, and the resulting HMPs were characterized for particle size, encapsulation efficiency, in vitro release kinetics, cytocompatibility, antiproliferative activity against melanoma cells, and in vitro enzymatic degradability. The sol–gel protocol was optimized to minimize drug degradation during encapsulation. Results: Microparticles (20–111 µm) exhibited a hybrid composition with efficient cross-linking. Encapsulation efficiencies of 85–100% were achieved, aided by up to 10-fold higher drug solubility in the new oils compared to original ICOe. Release kinetics were sustained and linear (11–53 days), fastest for IGRe- and slowest for ICOLAe-based HMP. Enzymatic degradation reached up to 46% after 30 days in the presence of fungal lipases, twofold higher than previously published ICOe microparticles, with ICOLAe degrading fastest due to PLA incorporation. Encapsulated JMV5038 retained its cytotoxic efficacy against A375 melanoma cells. Conclusions: These results highlight the promising use of such microparticles as versatile carriers for the prolonged release of lipophilic and acid-sensitive drugs.