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芦丁纳米混悬剂在骨质疏松症治疗中的应用:粒径减小对口服生物利用度和活性的影响。

Rutin nanosuspension for potential management of osteoporosis: effect of particle size reduction on oral bioavailability, and activity.

机构信息

Department of Pharmaceutics, NIPER, Hyderabad, India.

Department of Regulatory and Toxicology, NIPER , Hyderabad, India.

出版信息

Pharm Dev Technol. 2020 Oct;25(8):971-988. doi: 10.1080/10837450.2020.1765378. Epub 2020 May 13.

Abstract

Clinical significance of Rutin (RUT) is limited by poor dissolution rate and low oral bioavailability. The study was designed to improve the physicochemical and therapeutic potential of the drug by formulating nanosuspension (NS) for osteoporosis. Rutin nanosuspension (RUT-NS) was prepared after screening a range of stabilizers and their combinations at a different concentration by antisolvent precipitation technique. Effect of precipitation on crystallinity (differential scanning calorimetry DSC, X-ray diffraction studies XRD), morphology (scanning electron microscopy, SEM) and chemical interaction (attenuated total reflectance fourier-transform infrared spectroscopy ATR-FTIR) were studied through biophysical techniques. An optimized nanosuspension exhibited a minimum particle size of 122.85 ± 5.02 nm with higher dissolution of RUT-NS (87. 63 ± 2.29%) as compared to pure drug (39.77 ± 2.8 6%). The enhanced intestine absorption and apparent permeability were achieved due to the improved particle size, surface area and dissolution. RUT-NS displayed greater (3 folds) AUC than pure drug. assays with RUT-NS depicted an increased cell proliferation, antioxidant (ROS) activity and osteocalcin production in MG-63 osteoblast cells. The augmented biochemical biomarkers and bone quality proved the protective effect of RUT-NS. The results supported RUT-NS as a potential therapy for maintaining bone health.

摘要

芦丁(RUT)的临床意义受到较差的溶解速率和低口服生物利用度的限制。本研究旨在通过为骨质疏松症配制纳米混悬剂(NS)来提高药物的物理化学和治疗潜力。通过抗溶剂沉淀技术,在不同浓度下筛选了一系列稳定剂及其组合,制备了芦丁纳米混悬剂(RUT-NS)。通过生物物理技术研究了沉淀对结晶度(差示扫描量热法 DSC、X 射线衍射研究 XRD)、形态(扫描电子显微镜,SEM)和化学相互作用(衰减全反射傅里叶变换红外光谱 ATR-FTIR)的影响。优化的纳米混悬剂表现出最小的粒径为 122.85±5.02nm,与纯药物(39.77±2.86%)相比,芦丁-NS 的溶解度更高(87.63±2.29%)。由于粒径、表面积和溶解度的提高,实现了增强的肠道吸收和表观渗透率。与纯药物相比,RUT-NS 的 AUC 增加了 3 倍。RUT-NS 对 MG-63 成骨细胞的增殖、抗氧化(ROS)活性和骨钙素产生的测定显示出更大的作用。增加的生化生物标志物和骨质量证明了 RUT-NS 的保护作用。结果支持 RUT-NS 作为维持骨骼健康的潜在治疗方法。

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