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Physicochemical properties and biocompatibility of a polymer-paclitaxel conjugate for cancer treatment

Authors Yang, Van S, Liu, Wang, Jiang X, Wang, Yu L

Published 21 October 2011 Volume 2011:6 Pages 2557—2566

DOI https://doi.org/10.2147/IJN.S25044

Review by Single-blind

Peer reviewer comments 3

Danbo Yang1, Sang Van2, Jian Liu2, Jing Wang1, Xinguo Jiang3, Yiting Wang1, Lei Yu1,2
1Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai, China; 2Biomedical Group, Nitto Denko Technical Corporation, Oceanside, CA; 3School of Pharmacy, Fudan University, Shanghai, China

Background: Poly(L-γ-glutamylglutamine) paclitaxel (PGG-PTX) conjugate is a non-diblock polymeric drug nanoparticle intended to improve the therapeutic index of paclitaxel. The purpose of the present study was to elucidate further the physicochemical properties of PGG-PTX in order to proceed with its clinical development.
Methods and results: PGG-PTX was designed by integration of a hydrophobic paclitaxel conjugate through an added hydrophilic glutamic acid onto poly(L-glutamic acid). The addition of a flexible glutamic linker between PGA and paclitaxel resulted in spontaneous self-assembly of a PGG-PTX conjugate into nanoparticles. The PGG-PTX conjugate was stable as a lyophilized solid form. An in vitro viability experiment showed that PGG-PTX was effective after a longer incubation period, the same trend as Taxol. In vitro studies using NCI-H460 and B16F0 cancer cells demonstrated significantly high cellular uptake after 30 minutes of incubation. The in vivo biocompatibility of PGG-PTX conjugate was evaluated in the NCI-H460 tumor model, the assessment of tissue seemed to be normal after 21 days of treatment.
Conclusion: These results are encouraging for further development of non-block polymeric paclitaxel nanoparticles for treatment of cancer.

Keywords: polymer conjugate, paclitaxel, poly(L-γ-glutamylglutamine), drug delivery, physicochemical properties, nanoparticles

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