Madecassoside, a triterpenoid saponin compound mainly isolated from the gotu kola herb (Centella asiatica), shows an extensive range of biological activities, including antiapoptotic, antioxidant, anti-inflammatory, moisturizing, neuroprotective, and wound healing effects. It has been highly used in the management of eczema, skin wounds, and other diseases. Due to poor oral bioavailability, membrane permeability, and intestinal absorption, the clinical application of the madecassoside is limited. Hence, a drug carrier system is needed that not only sustains the release of the madecassoside but also overcomes the drawbacks associated with its administration. Therefore, the authors prepared novel pH-responsive chitosan-based nanogels for the sustained release of madecassoside. Free radical polymerization technique was used for cross-linking of polymer chitosan and monomer methacrylic acid in the presence of cross-linker N′,N′-methylene bis(acrylamide). The decrease in polymer crystallinity after polymerization and development of nanogels was demonstrated by XRD and FTIR analysis. The effects of nanogel contents on polymer volume, sol–gel analysis, swelling, drug loading, and release were investigated. Results indicated that high swelling and maximum release of the drug occurred at pH 7.4 compared to pH 1.2 and 4.6, indicating the excellent pH-sensitive nature of the engineered nanogels. High swelling and drug release were perceived with the integration of a high quantity of chitosan, while a decline was observed with the high integration of N′,N′-methylene bis(acrylamide) and methacrylic acid contents. The same effects of nanogel contents were shown for drug loading too. Sol fraction was reduced, while gel fraction was enhanced by increasing the chitosan load, N′,N′-methylene bis(acrylamide), and methacrylic acid. The Korsmeyer–Peppas model of kinetics was trailed by all nanogel formulations with non-Fickian diffusion. The results demonstrated that prepared nanogels can be employed for sustained release of the madecassoside.

中文翻译：

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用于持续递送羟基积雪草苷的壳聚糖聚合物 pH 响应纳米凝胶的配制和体外评估

羟基积雪草苷是一种三萜皂苷化合物，主要从积雪草中分离出来，具有广泛的生物活性，包括抗细胞凋亡、抗氧化、抗炎、保湿、神经保护和伤口愈合作用。它被广泛用于治疗湿疹、皮肤伤口和其他疾病。由于羟基积雪草苷口服生物利用度、膜通透性和肠道吸收较差，其临床应用受到限制。因此，需要一种药物载体系统，该系统不仅能够维持羟基积雪草苷的释放，而且能够克服与其给药相关的缺点。因此，作者制备了新型 pH 响应型壳聚糖纳米凝胶，用于持续释放羟基积雪草苷。采用自由基聚合技术在交联剂N',N'-亚甲基双丙烯酰胺存在下交联聚合物壳聚糖和单体甲基丙烯酸。 XRD 和 FTIR 分析证明了聚合和纳米凝胶发展后聚合物结晶度的降低。研究了纳米凝胶含量对聚合物体积、溶胶-凝胶分析、溶胀、载药量和释放的影响。结果表明，与 pH 1.2 和 4.6 相比，药物在 pH 7.4 时发生高溶胀和最大释放，表明工程纳米凝胶具有优异的 pH 敏感性。当壳聚糖含量高时，可观察到高溶胀和药物释放，而当N',N'-亚甲基双(丙烯酰胺)和甲基丙烯酸含量高时，观察到药物释放下降。纳米凝胶含量对于药物负载也显示出相同的效果。通过增加壳聚糖负载量、N',N'-亚甲基双(丙烯酰胺)和甲基丙烯酸，溶胶分数降低，而凝胶分数提高。所有具有非菲克扩散的纳米凝胶配方都遵循 Korsmeyer-Peppas 动力学模型。结果表明，制备的纳米凝胶可用于羟基积雪草苷的持续释放。