L-Amino Acid and Sugar-based Biodegradable Poly(ester-urethane) for Drug Delivery Applications

Abstract

Melt-condensation approach is well known for the transesterification to synthesise polyesters and was developed for synthesising polyurethanes and poly(ester-urethane) from our group by using amino-acid, a bioresource for the synthesis of monomer. Though amino acid makes the polymer biocompatible, the diols used in this condensation chemistry are petroleum-based, which doesn’t make the polymer completely biodegradable. By synthesising a sugar-based diol, the polymer is made completely biodegradable. The polymer self-assembles to form a nanocarrier capable of carrying drugs and would be easily degraded by the lysosomal enzymes. This makes the nanocarrier suitable for cancer treatment. The amino acid chosen is L-DOPA(l-3,4-dihydroxyphenylalanine); its carboxylic group is converted into ester, the amine group into urethane and the catechol group is silyl protected. The catechol unit allows for further functionalisation of the polymer side chain, which allows for a change in hydrophilicity of the polymeric side chain. The sugar diol is synthesised from D-mannitol by the acetal protection of secondary alcohol groups. The melt-condensation was done at 150°C, and the polymer was compared with other polymers synthesised using commercially available diols. They were characterised, and their thermal properties were studied. After deprotection of the silyl and acetal groups of the amino acid and sugar diol-based, fully biodegradable polymer, the dye and the drug loading were checked, and cell viability was studied for the nascent, the dye loaded and the drug-loaded polymer. The deprotected polymer was then loaded with the Nile Red dye and Doxorubicin(DOX) to check the drug and dye loading separately. The absorbance was measured, and using MTT assay, the cytotoxicity of the dye and drug were checked at various concentrations. Cellular uptake studies were also carried out. Poly(ester-urethane)s from our group synthesised by the melt-condensation approach are known to degrade by lysosomal enzymes. The complete biodegradability of the polymer would open a new method for developing polymeric nanomedicine, by the solvent-free melt-condensation approach, for cancer treatment.