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

Abstract

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, ChinaBackground: 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