Executive Summary : | Polymer nano-assemblies based on biological resources have gained significant interest due to their potential application in therapeutics, biodegradable and biocompatible engineering thermoplastics and so on. Among the natural resources, L-amino acids are important class of biological-monomers for producing well-defined macromolecular architectures. High molecular weight polypeptides that were explored for the biomedical applications have the limitation due to their very slow biodegradation s by protease enzymes. Very recently non-peptide polymer analogues have attained significant importance in biomedical field. From our research group, we have designed and developed new melt polycondensation approach for L-amino acid polymers under solvent free eco-friendly conditions and linear and hyperbranched polyesters and poly(ester-urethane)s were accomplished.
Functional polymers are next-generation polymeric biomaterials which provide ample opportunity for post-polymerization structural engineering to tune the scaffold properties to cater to the need of continuous demand in the bio-medical field. Unfortunately, these challenges are yet to be addressed in L-amino acid resource polymers; thus, comprehensive potential of naturally abundant L-amino acid resources are not entirely utilized in the polymer science and technology. In our continuous effort to explore the full potential of L-amino acid resources for biomaterial application, the above challenging task is taken up in the present proposal to explore “L-amino acid based multi-functional biodegradable polymer architectures” having large abundance of active functional groups such as hydroxyl, carboxylic acid and amines as next generation nano-scaffolds in biomedical research. These multi-functional biodegradable polymers will have following features: (i) anchoring of fluorophores for monitoring the intracellular events, (ii) provide new opportunity for drug-conjugation for in vitro and in vivo studies, (iii) facilitate the tagging of targeting ligands for receptor-mediated endocytosis and (iv) fine-tune the stimuli-responsiveness, (iv) opportunity to make lightly-cross-linked biodegradable nano-gel platform to enhance the drug loading and increase its stability. To accomplish above task, multi-functional L-amino acid resources such as L-aspartic acid, L-glutamic acid, L-lysine, L-tyrosine, L-serine, etc, would be employed to make thermally-stable monomers. Anticancer drugs such as doxorubicin, camptothecin and cisplatin will be chosen and both combination therapy as well targeted delivery based on biotin, folic acid or RGD peptide will also be explored. Further, AIE fluorophore will be anchored in the polymer nano-carriers to study real-time in vitro drug release kinetics. This problem is important from the perspectives of both fundamental knowledge generation in the area of polymer synthetic chemistry as well as new biomaterial development for application in cancer treatment. |