Block Copolymer Encapsulation of Disarib, an Inhibitor of BCL2 for Improved Chemotherapeutic Potential

A chemical inhibitor of antiapoptotic protein, BCL2, known as Disarib, suffers poor solubility in aqueous environments; thereby limiting its potential as a chemotherapeutic agent. To overcome this limitation and enhance the therapeutic efficacy of Disarib, we have employed the encapsulation of this small molecule inhibitor within P123 copolymer matrix. Micelles were synthesized using a thin-film hydration technique, and a comprehensive analysis was undertaken to evaluate the resulting micelle properties, including morphology, particle size, intermolecular interactions, encapsulation efficiency, and in vitro release characteristics. This assessment utilized various physicochemical techniques including UV spectroscopy, FTIR spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), and small-angle X-ray scattering (SAXS). Disarib-loaded P123 micelle formulation denoted as P123D exhibited a well-defined particle size of approximately 29.2 nm spherical core-shell morphology. Our investigations revealed a notable encapsulation efficiency of 75%, and we observed a biphasic release pattern for the encapsulated Disarib. Furthermore, our cytotoxicity assessment of P123D micelles against mouse breast adenocarcinoma, mouse lymphoma, and human leukemic cell lines showed 40-45% increase in cytotoxicity compared with the administration of Disarib alone in the breast adenocarcinoma cell line. Enhancement in the cytotoxicity of P123D was found to be higher or limited; however, it is important to observe that the encapsulation method significantly enhanced the aqueous solubility of Disarib as it has the best solubility in dimethyl sulfoxide (DMSO) in the unencapsulated state.