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Nanoscale cationic micelles of amphiphilic copolymers based on star-shaped PLGA and PEI cross-linked PEG for protein delivery application

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Abstract

To enhance the bioavailability of protein therapeutants and improve the stability of storage and delivery, a series of branched amphiphilic block copolymers consisting of cholic acid (CA) initiated poly(D,L-lactide-co-glycolide) (CA-PLGA) and water-soluble polyethyleneimine cross-linked polyethylene glycol (PEI-PEG) denoted as CA-PLGA-b-(PEI-PEG) were synthesized and characterized. CA-PLGA-b-(PEI-PEG) presented low cytotoxicity by MTT and cck-8 assay. The cationic CA-PLGA-b-(PEI-PEG) micelles (diameter about 100 nm and zeta potential 34–61 mV) were prepared through self-assembly method, and complexed with insulin via electrostatic interaction to obtain nanoscale micelle/insulin complexes. The micelle/insulin complexes-loaded CA-PLGA microspheres (MIC-MS, 10.4 ± 3.85 μm) were manufactured by employing a double emulsion (W1/O/W2) method. The in vitro insulin release behavior and in vivo hypoglycaemic effect of MIC-MS on streptozotocin (STZ) induced diabetic rats were compared with those of the insulin-loaded CA-PLGA microspheres (INS-MS, 7.8 ± 2.57 μm). The initial burst in vitro release of MIC-MS was markedly lower than that of INS-MS (P < 0.01), and the pharmacological availability of MIC-MS via subcutaneous administration was 148.9% relative to INS-MS. Therefore, the cationic CA-PLGA-b-(PEI-PEG) micelles can effectively increase the bioavailability of insulin in CA-PLGA microspheres and can be considered as a potential protein carrier.

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Acknowledgements

This work was funded by the National Natural Science Foundation of China (No. 81373365) and Guangdong Science and Technology Project (No. 2015A010105014).

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Authors and Affiliations

  1. Biomaterials Research Center, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China

    Jun Wang, Shunying Li, Tingting Chen, Lei Wu, Wenting Zhu & Qingbing Zeng

  2. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China

    Jun Wang, Shunying Li, Tingting Chen, Huiwu Zhang, Lei Wu, Wenting Zhu & Qingbing Zeng

  3. Department of Histology and Embryology, School of Basic Medicine, Southern Medical University, Guangzhou, 510515, China

    Wenjiao Xian

  4. Cancer Therapeutics & Drug Discovery Center, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China

    Huiwu Zhang

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Wang, J., Li, S., Chen, T. et al. Nanoscale cationic micelles of amphiphilic copolymers based on star-shaped PLGA and PEI cross-linked PEG for protein delivery application. J Mater Sci: Mater Med 30, 93 (2019). https://doi.org/10.1007/s10856-019-6294-y

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