Targeted Drug Delivery Using Polymeric Encapsulation for Enhanced Antineoplastic Activity

Targeted drug delivery systems enhance the therapeutic index of antineoplastic agents while minimizing side effects. This study focuses on the development of polymeric encapsulated submicron particles (PESP) for targeted delivery of Bis-(isothiocyanatomethyl) benzene, a purified compound (PC) with potent anticancer properties, as reported in our previous literature. Polyvinyl alcohol (PVA) was used to encapsulate the drug through a one-step modified binary nonsolvent coacervation technique, the details of which have been documented in Indian patent file no: 544591. It forms a spherical submicron particle with an average diameter of 0.3 µm and surface porosity ranging from 90 to 600 nm. The encapsulated PC exhibited enhanced cytotoxicity in breast cancer cell lines, especially in the mesenchymal MDA-MB-231 cells, while showing a safer profile for non-cancerous PBMCs compared to cisplatin. Cell viability assays demonstrated that PC-loaded PESP reduced cancer cell proliferation, particularly in MDA-MB-231 cells, which showed lower cell viability and higher apoptosis rates compared to hormone-responsive MCF-7 cells. Anchorage-independent growth assays further confirmed the anti-metastatic activity of PC-loaded PESP, effectively inhibiting soft agar colony formation in MDA-MB-231 cells. Apoptosis mechanisms differed between cell lines, with PC-loaded PESP triggering caspase 8 activation via the epidermal growth factor receptor (EGFR) in MDA-MB-231 cells and caspase 9 activation through mitochondrial pathways in MCF-7 cells. Molecular docking studies revealed strong binding affinities of PC with estrogen receptor (ER) and EGFR, supporting its role as an antagonist in promoting cancer cell apoptosis. The findings highlight PC-loaded PESP as a promising drug delivery system for targeting aggressive breast cancer subtypes, offering both cytotoxic and anti-metastatic properties.