Synthesis, Characterization and In Vitro Evaluation of Self-Assembled poly(ethylene glycol)-glycyrrhetinic Acid Conjugates

Gu      He; Zhiyao      He; Xi      Zheng; Junmin      Li; Chi      Liu; Xiangrong      Song; Liang      Ouyang; Fengbo      Wu

Abstract

Glycyrrhetinic acid (GA) is a commonly used drug for the chemotherapy of Chronic Hepatitis B, allergic dermatitis, inflammation, etc. But some problems such as poor water-solubility, low bioavailability and short plasma halflife, have limited its use. In the present study, PEGylation derivatives of GA derivatives were synthesized and characterized by FTIR, NMR, transmission electron microscopy, particle size analysis, etc. The PEG-GA conjugates having a critical micelle concentration of 0.081-0.73 mg/mL were used to form nano-sized micelles, with mean diameters of 120.86 ± 31.74 nm. The physico-chemical properties of the PEG – GA conjugate were evaluated including stability, cellular toxicity, and drug release profile. All the conjugates synthesized showed good stabilities in acidic and neutral solutions, while the stability in alkaline solution and the enzymatic hydrolysis rate, were significantly affected by the linkage between the GA and PEG chain. The results demonstrate that, by PEGylation of GA derivatives, the greatly increased water solubility and desirable self-assembly abilities of PEG-GA were obtained. The novel conjugates have potential medical applications for intravenously delivery of insoluble drug delivery.

Keywords: Glycyrrhetinic acid, in vitro evaluation, micelles, poly(etylene glycol), self assembly, antitumor activities, glycyrrhizic acid, drug delivery, nontoxic, biocompatible