posted on 2016-11-20, 00:00authored byRajendra Aluri, Manickam Jayakannan
New classes of enzymatic-biodegradable
amphiphilic poly(ester-urethane)s
were designed and developed from l-tyrosine amino acid resources
and their self-assembled nanoparticles were employed as multiple drug
delivery vehicles in cancer therapy. The amine and carboxylic acid
functional groups in l-tyrosine were converted into dual
functional ester-urethane monomers and they were subjected to solvent
free melt polycondensation with hydrophilic polyethylene glycols to
produce comb-type poly(ester-urethane)s. The phenolic unit in the l-tyrosine was anchored with hydrophobic alkyl side chain to
bring appropriate amphiphilicity in the polymer geometry to self-assemble
them as stable nanoscaffolds in aqueous medium. The topology of the
polymer was found to play a major role on the glass transition, crystallinity,
and viscoelastic rheological properties of l-tyrosine poly(ester-urethane)s.
The amphiphilic polymers were self-assembled as 200 ± 10 nm nanoparticles
and they exhibited excellent encapsulation capabilities for anticancer
drugs such as doxorubicin (DOX) and camptothecin (CPT). In vitro drug
release studies revealed that the drug-loaded l-tyrosine
nanoparticles were stable at extracellular conditions and they underwent
enzymatic-biodegradation exclusively at the intracellular level to
release the drugs. Cytotoxicity studies in the cervical cancer (HeLa)
and normal WT-MEFs cell lines revealed that the nascent l-tyrosine nanoparticles were nontoxic, whereas the CPT and DOX drug-loaded
polymer nanoparticles exhibited excellent cell killing in cancer cells.
Confocal microscopic imaging confirmed the cellular internalization
of drug-loaded nanoparticles. The drugs were taken up by the cells
much higher quantity while delivering them from l-tyrosine
nanoparticle platform compared to their free state. Flow cytometry
analysis showed that the DOX-loaded polymer nanoscaffolds internalized
the drugs 8–10× higher compared to free DOX. Both the
synthesis of new classes of poly(ester-urethane)s via melt polycondensation
approach and the enzyme-responsive drug delivery concept were accomplished
for the first time. Thus, the present investigation is expected to
open up new opportunities for l-tyrosine polymeric materials
in biomaterial and thermoplastic applications.