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

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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.

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ACKNOWLEDGMENTS

This work was supported by the National Natural Science Foundation of China (no. 30901864), Major National Platform for Innovative Pharmaceuticals (2009zx09301-012), Key Laboratory of Drug Preparation Design & Evaluation of Liaoning Provincial Education Department (2009s100), and the Program for Excellent Talents in the University of Liaoning Provincial Education Department.

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, P.O. Box 32, No.103 Wenhua Road, Shenyang, 110016, People’s Republic of China

    Hong Huo, Yikun Gao, Tianyi Wang, Haitao Jiang, Siling Wang & Tongying Jiang

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  1. Hong Huo
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  2. Yikun Gao
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  3. Tianyi Wang
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  4. Haitao Jiang
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  5. Siling Wang
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  6. Tongying Jiang
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Correspondence to Siling Wang or Tongying Jiang.

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Huo, H., Gao, Y., Wang, T. et al. The Investigation on Polyion Complex Micelles Composed of Diammonium Glycyrrhizinate/Poly(Ethylene Glycol)–Glycidyltrimethylammonium Chloride-Grafted Polyasparthydrazide. AAPS PharmSciTech 13, 1367–1376 (2012). https://doi.org/10.1208/s12249-012-9858-4

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  • DOI: https://doi.org/10.1208/s12249-012-9858-4

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