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壳聚糖-聚丙交酯/透明质酸复合微球作为生物活性转化生长因子-β1控释载体

Chitosan-Polylactide/Hyaluronic Acid Complex Microspheres as Carriers for Controlled Release of Bioactive Transforming Growth Factor-β1.

作者信息

Min Qing, Liu Jiaoyan, Li Jing, Wan Ying, Wu Jiliang

机构信息

School of pharmacy, Hubei University of Science and Technology, Xianning 437100, China.

College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.

出版信息

Pharmaceutics. 2018 Nov 17;10(4):239. doi: 10.3390/pharmaceutics10040239.

DOI:10.3390/pharmaceutics10040239
PMID:30453642
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6321178/
Abstract

Chitosan(CH)-polylactide(PLA) copolymers containing varied PLA percentages were synthesized using a group-protection method and one of them with solubility in water-based solvents was used to prepare CH-PLA/hyaluronic acid (HA) complex microspheres for the delivery of transforming growth factor-β1 (TGF-β1). An emulsification processing method was developed for producing TGF-β1-loaded CH-PLA/HA microspheres using sodium tripolyphosphate (TPP) as ionic crosslinker and the size of the microspheres was devised to the micron level in order to achieve high encapsulating efficiency. The encapsulating efficiency, swelling property and release administration of the microspheres could be synergistically regulated by PLA component, the applied TPP dose and the incorporated HA amount. In comparison to CH/HA microspheres, the CH-PLA/HA microspheres had greatly reduced TGF-β1 release rates and were able to administrate the TGF-β1 release at controlled rates over a significant longer period of time. The released TGF-β1 was detected to be bioactive when compared to the free TGF-β1. These results suggest that the presently developed CH-PLA/HA complex microspheres have promising potential in delivering TGF-β1 for cartilage repair applications where the applied TGF-β1 amount in the early stage needs to be low whilst the sustained TGF-β1 release at an appropriate dose in the later stage has to be maintained.

摘要

采用基团保护法合成了不同聚乳酸（PLA）含量的壳聚糖（CH）-聚乳酸共聚物，并使用其中一种可溶于水基溶剂的共聚物制备了用于递送转化生长因子-β1（TGF-β1）的CH-PLA/透明质酸（HA）复合微球。开发了一种乳化加工方法，以三聚磷酸钠（TPP）作为离子交联剂来制备负载TGF-β1的CH-PLA/HA微球，并将微球尺寸设计为微米级，以实现高包封率。微球的包封率、溶胀性能和释放行为可通过PLA组分、TPP用量和HA掺入量协同调节。与CH/HA微球相比，CH-PLA/HA微球的TGF-β1释放速率大大降低，并且能够在更长的时间内以可控速率释放TGF-β1。与游离TGF-β1相比，检测到释放的TGF-β1具有生物活性。这些结果表明，目前开发的CH-PLA/HA复合微球在递送TGF-β1用于软骨修复应用方面具有广阔的潜力，在该应用中，早期所需的TGF-β1用量较低，而后期必须维持适当剂量的TGF-β1持续释放。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01c/6321178/3440fa2dcc76/pharmaceutics-10-00239-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01c/6321178/3f7f38a11bbd/pharmaceutics-10-00239-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01c/6321178/dafd04a471db/pharmaceutics-10-00239-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01c/6321178/1514e487f094/pharmaceutics-10-00239-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01c/6321178/f83358443c2b/pharmaceutics-10-00239-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01c/6321178/3440fa2dcc76/pharmaceutics-10-00239-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01c/6321178/3f7f38a11bbd/pharmaceutics-10-00239-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01c/6321178/dafd04a471db/pharmaceutics-10-00239-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01c/6321178/1514e487f094/pharmaceutics-10-00239-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01c/6321178/f83358443c2b/pharmaceutics-10-00239-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01c/6321178/3440fa2dcc76/pharmaceutics-10-00239-g005.jpg

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