L-DOPA Based Enzyme Responsive Poly(ester-urethane)s for Drug Delivery Application

Abstract

L-dopa based enzyme degradable novel poly(ester-urethane)s were designed and developed through melt poly-condensation process. To achieve this, the amine and carboxylic acid moiety of the amino acid were suitable modified to ester and urethane containing different protecting groups on the catechol moiety. These monomers were subjected to melt poly-condensation with 1,12-dodecanediol to yield poly(ester-urethane)s. To introduce amphiphilicity into the polymer, tyrosine based monomer containing hydrophilic side chain also synthesized and polymerized with L-dopa based monomers to produce amphiphilic random copoly(ester-urethane)s containing various L-dopa composition. The structures of L-dopa based monomers and their corresponding poly(ester-urethane)s were confirmed by 1H and 13C NMR spectroscopy. The silyl protected homopolymer was deprotected to synthesize the polymer containing free catechol pendent unit. The molecular weights of the poly(ester-urethane)s was determined by GPC which showed mono-model distribution. The polymer properties such as decomposition temperature, glass transition temperature and water contact angle of these novel poly(ester-urethane)s were significantly varied with the change in the protection group on the catechol pendent unit of polymer chain. The random co-polymers synthesized from silyl protected L-dopa monomer and tyrosine based monomer was deprotected to produce amphiphilic polyester-urethane containing free catechol unit. These amphiphilic poly(ester-urethane)s were self-assembled in aqueous medium and polymer containing free catechol unit showed significant encapsulation of 6.2% for electron deficient anticancer drug doxorubicin (DOX). The size of the DOX-loaded polymer nanoparticles were found to be 138 ± 10 nm which is ambient for drug delivery application. The drug release kinetic experiment showed that the polymer nanoparticle are stable at physiological conditions and can be enzymatically biodegradable in lysosomal compartments to release the drug. Cytotoxic studies of this L-dopa based poly (ester-urethane) showed that the nanoparticles are non-toxic to MCF-7 cells