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Synthesis, characterization, and biological evaluation of poly(L-γ-glutamyl-glutamine)-paclitaxel nanoconjugate

Authors Van S, Das SK, Wang X, Feng Z, Jin Y, Hou Z, Chen F, Pham A, Jiang N, Howell SB, Yu L

Published 11 October 2010 Volume 2010:5 Pages 825—837

DOI https://doi.org/10.2147/IJN.S13482

Review by Single-blind

Peer reviewer comments 3

Sang Van1, Sanjib K Das1, Xinghe Wang1, Zhongling Feng1, Yi Jin1, Zheng Hou1, Fu Chen1, Annie Pham1, Nan Jiang1, Stephen B Howell2, Lei Yu1
1Nitto Denko Technical Corporation, Oceanside, CA, USA; 2Moores Cancer Center, University of California, La Jolla, San Diego, CA, USA

Abstract: The purpose of this study was to develop a novel, highly water-soluble poly(L-γ-glutamyl-glutamine)-paclitaxel nanoconjugate (PGG-PTX) that would improve the therapeutic index of paclitaxel (PTX). PGG-PTX is a modification of poly(L-glutamic acid)-paclitaxel conjugate (PGA-PTX) in which an additional glutamic acid has been added to each glutamic side chain in the polymer. PGG-PTX has higher water-solubility and faster dissolution than PGA-PTX. Unlike PGA-PTX, PGG-PTX self-assembles into nanoparticles, whose size remains in the range of 12–15 nm over the concentration range from 25 to 2,000 µg/mL in saline. Its critical micellar concentration in saline was found to be ~25 µg/mL. The potency of PGG-PTX when tested in vitro against the human lung cancer H460 cell line was comparable to other known polymer-PTX conjugates. However, PGG-PTX possesses lower toxicity compared with PGA-PTX in mice. The maximum tolerated dose of PGG-PTX was found to be 350 mg PTX/kg, which is 2.2-fold higher than the maximum tolerated dose of 160 mg PTX/kg reported for the PGA-PTX. This result indicates that PGG-PTX was substantially less toxic in vivo than PGA-PTX.

Keywords: nanoconjugates, poly(L-glutamic acid), poly(L-γ-glutamyl-glutamine)-paclitaxel, nanoparticles, anticancer

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