Synthesis And In Vitro Evaluation Of Functional Poly(L-glutamic Acid-co-L-lysine)

Synthetic polypeptide, one of the most important biodegradable polymers, hasfound wide uses in biomedical application such as drug delivery, tissue engineering,diagnostics and biosensors. Polypeptide has the superiority of biocompatibility andLow immunogenicity, which indicate wide used as drug career.As there are many kinds of side-chain functional groups that can react with targetdrugs, the polypeptide can be well used as drug career in medical science. But, therestill many problems with the single amino acid polymer (such as solubility andCytotoxicity), generally, we bring one or two other constituents into the polypeptide,to yield a new functional copolymer that could avoiding these defects.At the time being, there are four main strategies available to modify polypeptide:(1) copolymerization with ether to yield a polypeptide-co-polyether;(2)copolymerization with chitin to yield a polypeptide-co-chitin;(3) copolymerizationwith polyester to yield a polypeptide-co-polyester;(4) two kinds of amino acidcopolymerization to yield a co-polypeptide. These changes partly influence thephysical and chemical properties, which made the materials suitable for using asbiocompatible polymer.In the present study, P(Glu-co-Lys) was prepared through the randomcopolymerization of BLG-NCA and ZLys-NCA in DMF using n-hexylamine asinitiator, first BLG-NCA and ZLys-NCA reacted in DMF to get P(BLG--co-ZLys).Then P(BLG--co-ZLys) was dissolved in trifluoroacetic acid and then HBr/acetic acid(33wt%) was added, after the Deprotection, one could get the P(Glu-co-Lys) thatthere’s pH sensitive carboxyl and amine on the side. By changing the L-glutamicacid/L-lysine ratio (Glu/Lys), the surface charge of the P(Glu-co-Lys) nanoparticleswas expected to be reversed to positive from negative when the pH decrease to6.8(Tumor extracellular pH) from7.4(Blood pH), so that the P(Glu-co-Lys)nanoparticles have pH sensitivity, its structure were proved by H NMR、C NMR andnanoparticales were detected through DLS, FI and TEM.In this article, the cis-diaminodichloroplatinum (CDDP) and Adriamycin (DOX)were loading into the nanoparticales by dialysis, then surface charge of thesynthesized CDDP/P(Glu-co-Lys) and DOX/P(Glu-co-Lys) also influenced by drugloading content. The MTT assay proved when the L-glutamic acid ratio higher thanthe L-lysine, the material display low cytotoxicity and biocompatible, which mean could be used as drug nanocareer. These nanoparticles of CDDP/P(Glu-co-Lys) andDOX/P(Glu-co-Lys) displayed obvious cell inhibition. All the properties indicate thatthe co-polypeptide were suitable for the application as potential pH sensitive drugcareer.