The Investigation on Polyion Complex Micelles Composed of Diammonium Glycyrrhizinate/Poly(Ethylene Glycol)–Glycidyltrimethylammonium Chloride-Grafted Polyasparthydrazide

Abstract

Abstract. To prepare stable polyion complex (PIC) micelles, polyasparthydrazide (PAHy) modified with glycidyltrimethylammonium groups and methoxy poly(ethylene glycol) (mPEG) (mPEG-g-PAHy-GTA) was synthesized. The cytotoxicity of the polymer was evaluated by the methyl tetrazolium assay. The polymer entrapped the diammonium glycyrrhizinate (DG) and formed polyion complexes. The effect of pH value, grafting degree of mPEG, copolymer and drug concentration on the micelle formation was investigated by means of measuring entrapment efficiency and micelle size. In vitro DG release from the PIC micelles was detected by dialysis in various media of different ionic strengths. To examine the pharmacokinetic behavior of micelles in vivo, the time course of the drug in plasma was evaluated. The cytotoxicity of the polymer was very low. The results showed that entrapment efficiency can reach about 93%, and the mean particle size was almost 50 nm. The drug release rate decreased with a decrease in ionic strength of the release medium or an increase in the PEG grafting degree. Compared with DG solution, the AUC of DG micelles had a twofold increase. The smaller clearance and longer mean residence time of the DG micelles group compared with DG solution group showed that the DG loaded in PIC micelles can reduce drug elimination and prolong the drug residence time in the blood circulation. The results indicated that PIC micelles composed of mPEG-g-PAHy-GTA would be prospective as a drug carrier to the drugs which can be ionized in solution.

Polyion complex micelles composed of pegylated polyasparthydrazide derivatives for siRNA delivery to the brain

“…The ratio of GTA grafted onto PAHy side chain was defined as the grafting degree (GD, mol%) (GD of GTA = trimethylammonium groups/the L-aspartic acid units). The grafting degree was 32% as reported before [14].…”

“…PAHy-GTA was synthesized and characterized according to the previously reported procedure [14]. Briefly, polysuccimide (PSI) was synthesized by the polycondensation of L-aspartic acid [17].…”

“…In order to solve the problem of micelles across BBB in vivo, on the basis of our previous studies we design a novel polymer modified with brain targeting ligand for siRNA delivery to the brain. In previous work, polyasparthydrazide modified with methoxy PEG and trimethylammonium groups (mPEG-g-PAHy-GTA) was synthesized [14]. Then the synthesized polymer entrapped diammonium glycyrrhizinate (DG) and formed PIC micelles which can release DG in response to ionic strength.…”

Engineering biodegradable micelles of polyethylenimine-based amphiphilic block copolymers for efficient DNA and siRNA delivery

“…Incorporation of PEG-CG during micelle formation could strongly affect the micelle-DNA interactions, as both particle size and zeta potential were altered at the presence of PEG-CG. It has been suggested that the PEG corona could prevent the aggregation of micelles or micellebased nanocomposites due to a steric repulsion between the PEG chains [42][43][44][45]. This may explain that sizes of polyplex particles containing PEG-CG were smaller than those without PEG-CG for most of the N/P ratios ( Fig.…”