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Folate-conjugated star branched PLLA-b-(PEG)2 copolymer as nanocarrier for targeted delivery
Annual Conference and Expo on Biomaterials
Ing-Hong Ooi, See-Kiat Wong, Ismail Zainol and Mei-Peng Ng
International Medical University, Malaysia University Pendidikan Sultan Idris, Malaysia Taylorâ??s University, Malaysia
ScientificTracks Abstracts: J Biotechnol Biomater
Abstract
Folate-conjugated star-branched poly(L-lactide)-block-[poly(ethylene glycol)] copolymer are of interest as tumor-specific drug delivery system, targeting cancerous tumors overexpressed with folate receptors via receptor mediated cellular uptake mechanism. The primary objective of this study was to synthesize and characterize folate-conjugated four-arm star-branched PLLA-b-(PEG)2 copolymers. The 4-arm star-branched copolymers with folate groups attached to the PEG chain ends were synthesized by a multi step procedure using ring opening polymerization and carbodiimide chemistry strategies. Briefly, in the first step, four-arm star-branched PLLA was synthesized by a ring opening polymerization of L-lactide in the presence of pentaerythritol as initiator and 4-dimethylaminopyridine DMAP/DMAP HOSO2CF3 as catalyst. The resulting polymer was activated with 4-nitrophenyl chloroformate (4-NPC), which was then reacted with aminoadipic acid (AAA) to afford AAAterminated four-arm PLLA (P1). An ?±-amino-Ï?-folate-PEG was conjugated to P1 via carbodiimide chemistry to produce the title star-branched PLLA-b-(PEG)2 copolymer (P2). All synthesized polymers were precipitated in diethyl ether/methanol mixture followed by centrifugation and then purification by membrane dialysis against deionized water using Spectra/Por membrane of appropriate molecular weight cut-off size, before being freeze-dried. FTIR and 1H NMR and GPC techniques were used to characterize and confirmed the synthesized intermediates as well as the target polymer P2. The nanoparticles of P2 loaded with a model drug were fabricated by using a modified emulsion solvent evaporation technique. The resulting nanoparticles average sizes ranged from 178-211 nm with PDIs from 0.121 to 0.235 and zeta potentials from -13.2 to -19.9 mV before and after freeze drying. The drug release and cytotoxicity studies of the nanoparticles will be presented.Biography
Ing-Hong Ooi has obtained his PhD in 1998 from the University of Akron, Ohio, USA. He is currently the Head of the Department of Pharmaceutical Chemistry and Senior Lecture in the School of Pharmacy, International Medical University, Malaysia.
Email: inghong_ooi@imu.edu.my
