Combretastatin A4/poly(L-glutamic acid)-graft-PEG conjugates self-assembled to nanoparticles

Yang Ou; Zhao-Hui Tang; Lu Sun; Hai-Yang Yu; Jia Li; Mei-Hui Zhao; Hui Xu

doi:10.1016/j.ajps.2017.10.001

Combretastatin A4/poly(L-glutamic acid)-graft-PEG conjugates self-assembled to nanoparticles

Asian J Pharm Sci. 2018 Mar;13(2):191-196. doi: 10.1016/j.ajps.2017.10.001. Epub 2017 Oct 24.

Authors

Yang Ou^{1

2}, Zhao-Hui Tang², Lu Sun¹, Hai-Yang Yu², Jia Li¹, Mei-Hui Zhao¹, Hui Xu¹

Affiliations

¹ School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
² Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.

Abstract

Combretastatin A4 (CA4) possesses varying ability to cause vascular disruption in tumors, while the short half-life, low water solubility and deactivation of many CA4 analogs during storage limited its antitumor efficacy and drug stability. A novel macromolecular conjugate of CA4 (CA4-PL) was synthesized by covalent bonding of CA4 onto poly(L-glutamic acid)-graft-polyethylene glycol (PLG-g-PEG) via Yamaguchi reaction. The obtained CA4-PL was characterized by ¹H NMR, GPC, and UV methods, and the properties of the nanoparticles composed of CA4-PL, including critical aggregation concentration, size and size distribution, and morphology, were investigated. CA4-PL can self-assemble to form micelle-like nanoparticles of 80~120 nm in diameter, which may have potential to improve the blood circulation period as well as the targetability of CA4, and find applications to treat various tumors when combined with traditional chemotherapy or radio therapy.

Keywords: Combretastatin A4; Macromolecular conjugate; Nanoparticles; Poly(L-glutamic acid)-graft-polyethylene glycol; Self-assemble.