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mPEG-PLA 和 PLA-PEG-PLA 纳米粒作为新型载体用于重组人生长激素(rhGH)的递送。

mPEG-PLA and PLA-PEG-PLA nanoparticles as new carriers for delivery of recombinant human Growth Hormone (rhGH).

机构信息

Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, 14115-175, Iran.

Polymer Engineering Department, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, 14115-114, Iran.

出版信息

Sci Rep. 2018 Jun 29;8(1):9854. doi: 10.1038/s41598-018-28092-8.

Abstract

mPEG-PLA and PLA-PEG-PLA copolymeric nanoparticles with three different PLA to PEG ratios are synthesized and used for encapsulation of recombinant human Growth hormone (rhGH). The structure and composition of the synthesized copolymers were analyzed by H NMR and GPC techniques. Moreover, morphology, encapsulation efficiency (EE), cytotoxicity, release profile and stability of the encapsulated rhGH were measured. Structural analysis of the prepared copolymers showed that they were successfully synthesized with approximately expected molecular weight and relatively low size distribution. It was also revealed that by increasing amounts of PLA/PEG ratio, EE content and size of nanoparticles were increased. Release profile evaluation of rhGH from both formulations indicated that copolymeric nanoparticles of Di-B2 and Tri-B2 exhibited the best results among the synthesized nanospheres, by having initial burst release of 17.5% and 28% and then slow and constant release of rhGH up to 65% and 77% of the encapsulated drug, respectively. Furthermore, results of HPLC, SDS-PAGE and CD analyses showed stability of rhGH during encapsulation and release from nanoparticles. Finally, the results showed that these two formulations provided safe and efficient sustained release of rhGH for more than a month and they have the potential to do further studies under in vivo conditions.

摘要

采用三种不同 PLA 与 PEG 比例的 mPEG-PLA 和 PLA-PEG-PLA 共聚物纳米粒来包封重组人生长激素(rhGH)。通过 1H NMR 和 GPC 技术对合成共聚物的结构和组成进行了分析。此外,还测量了包封 rhGH 的形态、包封效率(EE)、细胞毒性、释放曲线和稳定性。对所制备的共聚物的结构分析表明,它们成功地合成了具有预期分子量和相对较低的分子量分布的共聚物。结果还表明,随着 PLA/PEG 比例的增加,纳米粒的 EE 含量和粒径增加。rhGH 从两种制剂的释放曲线评估表明,Di-B2 和 Tri-B2 共聚物纳米球表现出最佳的结果,分别具有 17.5%和 28%的初始突释,然后rhGH 缓慢且持续释放,分别达到包封药物的 65%和 77%。此外,HPLC、SDS-PAGE 和 CD 分析结果表明,rhGH 在包封和从纳米粒中释放过程中的稳定性。最后,结果表明,这两种制剂为 rhGH 的安全有效的持续释放提供了超过一个月的时间,并且它们有可能在体内条件下进行进一步的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca6a/6026132/2472cbf2a766/41598_2018_28092_Fig1_HTML.jpg

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