Development OF L-Aspartic acid Based Polyesters and Their Nano-assemblies in Drug Delivery

Abstract

New classes of amide-functionalized L-aspartic acid polyesters were designed and developed through solvent-free melt poly-condensation approach and explored self-assembled cationic amphiphilic nanoparticles as drug carrier for cancer cells. For this purpose, natural resource L-aspartic monomers were synthesised through tailor-made approaches with benzoyl, acetyl and naphthoyl amide pendant groups. These aspartic acid monomers were subjected to melt poly-condensation with various aliphatic diols to yield high molecular weight polyesters. The structures of aspartic acid monomers and their corresponding polyesters were confirmed by 1H and 13C NMR spectroscopy. The molecular weight of the polyesters was determined by GPC which showed mono-model distribution. MALDI-TOF MS end group analysis confirmed that the aspartic acid monomers were thermally stable under the melt condensation and there were mainly three types of polymer linear chains. The thermal properties such as glass transition temperature and semi-crystallinity of these new polyesters were significantly varied with the change in the amide functionality in the polymer pendants. Amide and BOC-protected random co-polyesters were made by using L-aspartic acid monomers having acetyl-amide and BOC-pendent units with 1,12-dodecanediol. The selective deprotection of the BOC group in the pendant unit yielded cationic and amphiphilic co-polyesters having positive charge in the backbone. These cationic polymers self-assembled in aqueous medium and showed a size of 2105nm and they showed excellent capability to encapsulate fluorophore such as Nile red and anticancer drugs such as doxorubicin (DOX). Confocal and flow cytometry analysis proved that these cationic polyester nanoparticles were stable and readily taken up by the cancer cells in significant quantity. Cytotoxic studies of the cationic polyester showed that the nanoparticles are non-toxic to HeLa cells.