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载雷奈酸锶功能化壳聚糖纳米粒的骨质疏松治疗作用增强:制剂研发、体内和分子模拟研究。

Improved treatment efficacy of risedronate functionalized chitosan nanoparticles in osteoporosis: formulation development, in vivo, and molecular modelling studies.

机构信息

a Department of Pharmacology , M. S. Ramaiah University of Applied Sciences , Bengaluru , India.

b Department of Pharmaceutics , M.S. Ramaiah University of Applied Sciences , Bengaluru , India.

出版信息

J Microencapsul. 2019 Jun;36(4):338-355. doi: 10.1080/02652048.2019.1631401. Epub 2019 Jun 27.

Abstract

Delivery of bisphosphonates-like risedronate has been a major challenge till date due to its poor bioavailability and gastrointestinal tract adverse effects. In this study, we explored the prospective use of risedronate functionalised chitosan nanoparticle (RISCN) for management and treatment of osteoporosis. The prepared nanoparticle was characterised by using scanning electron microscopy, atomic force microscopy, and dynamic light scattering technique. Osteoporosis was induced on quarantined female Wistar rats and treated with RISCN. Docking studies were performed to establish the molecular mechanism of RISCN in improving the bone microarchitecture. Results indicated that there was a significant improvement in bone mineral density and healing of trabecular microarchitecture with less cortical porosity on the bone surfaces of the treatment groups. Docking studies indicated a high affinity and binding of chitosan and RISCN towards the human farnesyl diphosphate synthase (FDPS). Thus, a novel risedronate-loaded chitosan nanoparticle revealed promising results in an effective bone bridging process and osteoporosis treatment.

摘要

由于生物利用度差和胃肠道副作用,双膦酸盐类药物利塞膦酸盐的递送一直是一个主要挑战。在这项研究中,我们探索了利塞膦酸盐功能化壳聚糖纳米粒子(RISCN)在骨质疏松症管理和治疗中的应用前景。使用扫描电子显微镜、原子力显微镜和动态光散射技术对制备的纳米粒子进行了表征。在隔离的雌性 Wistar 大鼠中诱导骨质疏松症,并使用 RISCN 进行治疗。进行对接研究以确定 RISCN 改善骨微结构的分子机制。结果表明,治疗组的骨表面骨矿物质密度显著提高,小梁微结构得到改善,皮质孔隙率降低。对接研究表明壳聚糖和 RISCN 与人法呢基二磷酸合酶(FDPS)具有高亲和力和结合性。因此,一种新型的利塞膦酸盐负载壳聚糖纳米粒子在有效的骨桥接过程和骨质疏松症治疗中显示出有希望的结果。

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