Lipid based block copolymers and conjugates for targeted delivery

Drug molecules face challenges like short half-life, in vivo instability, poor bioavailability, rapid degradation, and inappropriate distribution. Nanocarriers offer a solution, but successful targeted and controllable drug delivery remains a key challenge. This study focuses on synthesizing renewable lipid-based block copolymers for effective anti-cancer drug delivery.

A stearic acid-based methacrylate polymer (PSAMA) was microwave-synthesized and used to produce the thermoresponsive block copolymer PSAMA-b-PNIPAM. These self-assembled into ~30 nm nanoparticles with low CMC. The model drug, Carbamazepine (CBZ), achieved a loading efficiency of 31.6%, displaying temperature-triggered release lasting up to 84 h. Then we explored the impact of fatty acid types (PVS and PVL) on self-assembly. The block copolymer (PVS/PVL-b-PNVCL) showed highly tunable morphology and particle size. PVS-b-PNVCL micelles formed smaller, spherical structures (~80 nm), while PVL-b-PNVCL exhibited exclusive spherical morphology with larger sizes (130-145 nm). Micelles made from PVS-b-NVCL demonstrated high drug loading capacity for doxorubicin (DOX) with favorable biocompatibility. The protein-polymer bioconjugates (BSA-PVS-b-PNVCL) were then developed with well-defined structure, biocompatibility, and low cytotoxicity. In an aqueous environment, these self-assembled into vesicles (200 nm). DOX was encapsulated with a loading capacity of 25.6%, exhibiting effective in vitro antitumor activity and efficient cellular uptake. The lower critical solution temperature (LCST) was fine-tuned to around 40 oC, facilitating targeted drug delivery to tumors.
Overall, this study emphasizes the potential of renewable materials in advancing smart drug delivery platforms. The findings suggest promising advancements in biobased and biocompatible carrier systems for cancer therapies