Influence of micelle surface properties on the delivery of anti-cancer drugs

In our research, we carried out several analyses in order to investigate the nature of the shell of polymeric nanoparticles for drug delivery purposes. Firstly, a series of thermo-and pH-responsive poly(methyl methacrylate)-block-poly[methacrylic acid-co-di(ethylene glycol) methyl ether methacrylate] PMMA-b-P[MAA-co-DEGMA] block copolymers were synthesized by RAFT polymerization and self-assembled into nanoparticles. The release of the drugs was strongly dependent on the temperature and the measured cloud point temperature (Tcp) of the polymer. Systems below the Tcp released the drug slowly while increasing the temperature above the Tcp or decreasing the pH value to 5 resulted in the burst-like release of the drug. All the block copolymer micelles were taken up by the ovarian cancer cell line A2780, but with a noticeable decrease with increasing negative surface charge. ABZ delivered in this pH-responsive drug carrier had a higher toxicity than the free drug delivered in a non-responsive drug carrier. Secondly, a series of zwitterionic homopolymers were synthesized via two techniques: post-functionalization modification and direct polymerization. The ligands of interest in these studies were agmatine and glycine. Ligands were successfully substituted to PMAA and the highest agmatine conjugation efficiency (65%) was obtained when the reaction preceded using EDC/NHS/DBU ratios of 1, 2, 4, 2.5 in Milli-Q water for 48 hrs. Furthermore, N-(4-guanidinobutyl)methacrylamide was successfully synthesized using agmatine sulfate and copolymerized with 2-carboxyethyl acrylate (CEA) via PET-RAFT polymerization. The in vitro cytotoxicity tests confirmed that the final products obtained via post-functionalization modification and direct polymerization were nontoxic when treated to the human ovarian cancer cells (A2780)