Suhail Muhammad, Chiu I-Hui, Ullah Arif, Khan Arshad, Ullah Hamid, Al-Sowayan Noorah Saleh, Wu Pao-Chu
School of Pharmacy, Kaohsiung Medical University, 100 Shih-Chuan first Road, Kaohsiung 80708, Taiwan.
Institute of Biomedical Materials, School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, China.
ACS Omega. 2024 Apr 16;9(17):19345-19352. doi: 10.1021/acsomega.4c00461. eCollection 2024 Apr 30.
Madecassoside, a triterpenoid saponin compound mainly isolated from the gotu kola herb (), 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.
羟基积雪草苷是一种主要从积雪草中分离得到的三萜皂苷化合物，具有广泛的生物活性，包括抗凋亡、抗氧化、抗炎、保湿、神经保护和伤口愈合作用。它已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差、膜通透性和肠道吸收性不佳，其临床应用受到限制。因此，需要一种药物载体系统，既能维持羟基积雪草苷的释放，又能克服其给药相关的缺点。因此，作者制备了新型pH响应性壳聚糖基纳米凝胶用于羟基积雪草苷的缓释。在交联剂N',N'-亚甲基双丙烯酰胺存在下，采用自由基聚合技术使壳聚糖聚合物与甲基丙烯酸单体交联。通过XRD和FTIR分析证明了聚合后聚合物结晶度的降低和纳米凝胶的形成。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，纳米凝胶在pH 7.4时出现高溶胀和药物最大释放，表明所制备的纳米凝胶具有优异的pH敏感性。壳聚糖含量高时，纳米凝胶表现出高溶胀和药物释放，而N',N'-亚甲基双丙烯酰胺和甲基丙烯酸含量高时则观察到下降。纳米凝胶含量对载药量也有同样的影响。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，凝胶分数增加。所有纳米凝胶制剂均遵循非菲克扩散的Korsmeyer-Peppas动力学模型。结果表明，所制备的纳米凝胶可用于羟基积雪草苷的缓释。
