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

Publication date: March 2018Source: Asian Journal of Pharmaceutical Sciences, Volume 13, Issue 2Author(s): Yang Ou, Zhao-hui Tang, Lu Sun, Hai-yang Yu, Jia Li, Mei-hui Zhao, Hui XuAbstractCombretastatin 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.Graphical AbstractA novel macromolecular conjugate of CA4 was synthesized by covalent bonding of CA4 onto poly(L-glutamic acid)-graft-polyethylene glycol (PLG-g-PEG) via Yamaguchi reaction. As an amphiphilic macromolecule, CA4-PL can self-assemble to form nanosized particles in aqueous media.
Source: Asian Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Source Type: research