Executive Summary : | Breast cancer is a major global health concern, with multidrug resistant cancer cells overexpressing drug efflux pumps like P-glycoprotein (P-gp) to eliminate anticancer agents. Co-administration of a P-gp inhibitor with a neoplastic drug can enhance treatment efficacy by enhancing drug penetration and accumulation in cancer cells. Curcumin, a naturally occurring P-gp inhibitor, can suppress P-gp expression and down-regulate certain pathways, preventing drugs from entering cancerous cells. However, curcumin's poor solubility and stability limit its bioavailability and therapeutic efficacy. To overcome these limitations, a novel strategy is proposed: constructing amphiphilic polymers from curcumin that self-assemble into micelles in aqueous media and entrap neoplastic drug in its hydrophobic core. These micelles undergo hierarchical disassembly, resulting in the release of curcumin and drug. This enhances bioavailability, harnesses P-gp inhibition properties of curcumin, and enhances the potency of anticancer drugs for targeted breast cancer therapy. The structure of the polymers and micelles will be determined using various techniques, and the potential of carriers will be demonstrated through in vitro studies and in vivo breast cancer-induced mice models. The study opens up new areas of non-toxic, multi-stimuli responsive nanocarriers that can efficiently deliver therapeutic agents to specific tumor sites. Preclinical trials could be undertaken to utilize the project's outcomes for cancer therapy. |