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透明质酸-g-PPG 和 PEG-PPG-PEG 杂化温敏水凝胶用于延长凝胶稳定性和持续药物释放。

Hyaluronic acid-g-PPG and PEG-PPG-PEG hybrid thermogel for prolonged gel stability and sustained drug release.

机构信息

Department of Chemistry and Nanoscience, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Republic of Korea.

Department of Chemistry and Nanoscience, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Republic of Korea.

出版信息

Carbohydr Polym. 2022 Sep 1;291:119559. doi: 10.1016/j.carbpol.2022.119559. Epub 2022 May 2.

DOI:10.1016/j.carbpol.2022.119559
PMID:35698385
Abstract

Hyaluronic acid-graft-poly(propylene glycol) (HA-g-PPG) was prepared to induce hydrophobic interactions between HA-g-PPG and F127 PPGs (poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol)) and consequent increases in gel stability of F127 gel. Molecular weights of 340, 1000, and 2500 Da were used for PPG, and grafting ratios of HA-g-PPG varied over 3%, 12%, and 50%. Using rheology measurements, H NMR spectra, lower critical solution temperature measurements, dynamic light scattering, and transmission electron spectroscopy, hydrophobic crosslinking and intermicellar bridge formation were suggested in the aqueous HA-g-PPG/F127 hybrid solutions. In particular, the gel stability of the HA-g-PPG/F127 hybrid thermogel increased from 2 days (F127 only) to 6 days, thus the hybrid thermogel can provide longer delivery of an incorporated drug. The HA-g-PPG/F127 thermogel exhibited tissue compatibility in the subcutaneous layer of rats. The protein drug release from the gel indicated that interactions between negative charged HA-g-PPG and positive charged drug (calcitonin) reduced initial burst release.

摘要

透明质酸接枝聚丙二醇(HA-g-PPG)被用来诱导 HA-g-PPG 与 F127PPGs(聚乙二醇-聚丙二醇-聚乙二醇)之间的疏水相互作用,从而提高 F127 凝胶的稳定性。使用的 PPG 的分子量分别为 340、1000 和 2500Da,HA-g-PPG 的接枝率分别为 3%、12%和 50%。通过流变学测量、1H NMR 谱、低临界溶液温度测量、动态光散射和透射电子显微镜,在 HA-g-PPG/F127 混合水溶液中提出了疏水交联和胶束间桥接形成。特别是,HA-g-PPG/F127 杂化温敏凝胶的凝胶稳定性从 2 天(仅 F127)增加到 6 天,因此杂化温敏凝胶可以提供更长时间的药物包封。HA-g-PPG/F127 温敏凝胶在大鼠皮下层表现出组织相容性。从凝胶中释放的蛋白质药物表明,带负电荷的 HA-g-PPG 与带正电荷的药物(降钙素)之间的相互作用减少了初始突释。

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