Abstract：
This research investigated the in vivo gelation, biodegradation, and drug release efficiency of a novel injectable sensitive drug delivery system for human growth hormone (HGh). This composite system comprises pH- and temperature-sensitive hydrogel, designated as oligomer serine-b-poly(lactide)-b-poly(ethylene glycol)-b-poly(lactide)-b-oligomer serine (OS-PLA-PEG-PLA-OS) pentablock copolymer, as matrix and electrosprayed HGh-loaded chitosan (HGh@CS) nanoparticles (NPs) as principal material. The proton nuclear magnetic resonance spectrum of the pH- and temperature-sensitive OS-PLA-PEG-PLA-OS pentablock copolymer hydrogel proved that this copolymer was successfully synthesized. The HGh was encapsulated in chitosan (CS) NPs by an electrospraying system in acetic acid with appropriate granulation parameters. The scanning electron microscopy images and size distribution showed that the HGh@CS NPs formed had an average diameter of 366.1 ± 214.5 nm with a discrete spherical shape and dispersed morphology. The sol-gel transition of complex gel based on HGh@CS NPs and OS-PLA-PEG-PLA-OS pentablock hydrogel was investigated at 15 °C and pH 7.8 in the sol state and gelled at 37 °C and pH 7.4, which is suitable for the physiological conditions of the human body. The HGh release experiment of the composite system was performed in an in vivo environment, which demonstrated the ability to release HGh, and underwent biodegradation within 32 days. The findings of the investigation revealed that the distribution of HGh@CS NPs into the hydrogel matrix not only improved the mechanical properties of the gel matrix but also controlled the drug release kinetics into the systematic bloodstream, which ultimately promotes the desired therapeutic body growth depending on the distinct concentration used.
摘要：
这项研究调查了体内凝胶化，生物降解，新型人生长激素（HGh）可注射敏感给药系统的药物释放效率。该复合体系包含pH和温度敏感的水凝胶，指定为低聚物丝氨酸-b-聚（丙交酯）-b-聚（乙二醇）-b-聚（丙交酯）-b-低聚物丝氨酸（OS-PLA-PEG-PLA-OS）五嵌段共聚物，作为基质和电喷雾载HGh的壳聚糖（HGh@CS）纳米颗粒（NPs）作为主要材料。pH-和温度敏感的OS-PLA-PEG-PLA-OS五嵌段共聚物水凝胶的质子核磁共振谱证明成功合成了该共聚物。通过具有适当造粒参数的乙酸中的电喷雾系统将HGh封装在壳聚糖（CS）NP中。扫描电子显微镜图像和尺寸分布表明，形成的HGh@CSNPs的平均直径为366.1±214.5nm，具有离散的球形和分散的形态。研究了基于HGh@CSNP和OS-PLA-PEG-PLA-OS五嵌段水凝胶的复合凝胶在15°C和pH7.8的溶胶状态下的溶胶-凝胶转变，并在37°C和pH7.4的条件下凝胶化，适用于人体的生理条件。复合体系的HGh释放实验在体内环境中进行，证明了释放HGh的能力，并在32天内进行生物降解。研究结果表明，HGh@CSNPs在水凝胶基质中的分布不仅改善了凝胶基质的机械性能，而且还控制了药物在系统血流中的释放动力学。这最终促进所需的治疗体生长，这取决于所使用的不同浓度。
