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壳聚糖包封美洛昔康纳米粒用于持续药物递送应用:在 Wistar 大鼠中的制备、表征和药代动力学。

Chitosan Encapsulated Meloxicam Nanoparticles for Sustained Drug Delivery Applications: Preparation, Characterization, and Pharmacokinetics in Wistar Rats.

机构信息

Department of Veterinary Pharmacology and Toxicology, Veterinary College, Hebbal, Bengaluru 560 024, Karnataka, India.

Karnataka Veterinary, Animal and Fisheries Sciences University, Bidar 585 401, Karnataka, India.

出版信息

Molecules. 2022 Oct 27;27(21):7312. doi: 10.3390/molecules27217312.

Abstract

Meloxicam (MLX) is currently used in the therapeutic management of both acute and chronic inflammatory disorders such as pain, injuries, osteoarthritis, and rheumatoid arthritis in both humans and animals. Gastrointestinal toxicity and occasional renal toxicity were observed in patients taking it for a long-term period. Meloxicam's late attainment of peak plasma concentration results in a slow onset of action. The goal of the current study was to prepare and characterize chitosan encapsulated meloxicam nanoparticles (CEMNPs) with high bioavailability and less gastro intestinal toxicity in order to prevent such issues. The size of the prepared CEMNPs was approximately 110-220 nm with a zetapotential of +39.9 mV and polydispersity index of 0.268, suggesting that they were uniformly dispersed nanoparticles. The FTIR and UV-Vis spectroscopy have confirmed the presence of MLX in the prepared CEMNPs. The pharmacokinetics have been studied with three groups of male Wistar rats receiving either of the treatments, viz., 4 mg·kg of MLX and 1 or 4 mg·kg of CEMNPs. Plasma samples were collected until 48 h post administration, and concentrations of MLX were quantified by using reverse (C) phase HPLC. Non-compartmental analysis was applied to determine pharmacokinetic variables. Upon oral administration, the maximum concentration (C) was reached in 4 h for CEMNPs and 6 h for MLX. The mean area under the plasma MLX concentration-time curve from 'zero' to infinity (AUC), half-life (t), and mean resident time (MRT) of 1 mg·kg of CEMNPs was 1.4-, 2-, and 1.8-fold greater than 4 mg·kg of MLX. The prepared CEMNPs demonstrated quicker absorption and prolonged release along with a significant improvement in the bioavailability of MLX, paving a prospective path for the development of drugs with enhanced bioavailability with less side effects.

摘要

美洛昔康(MLX)目前被用于人类和动物的急性和慢性炎症性疾病的治疗管理,如疼痛、损伤、骨关节炎和类风湿关节炎。长期服用美洛昔康的患者会出现胃肠道毒性和偶尔的肾毒性。美洛昔康达到血浆峰值浓度的时间较晚,导致其作用缓慢。本研究的目的是制备和表征具有高生物利用度和较少胃肠道毒性的壳聚糖包封美洛昔康纳米粒(CEMNPs),以预防此类问题。制备的 CEMNPs 的粒径约为 110-220nm,Zeta 电位为+39.9 mV,多分散指数为 0.268,表明它们是均匀分散的纳米粒。傅立叶变换红外光谱(FTIR)和紫外可见光谱(UV-Vis)已证实 MLX 存在于制备的 CEMNPs 中。用三种雄性 Wistar 大鼠组进行了药代动力学研究,分别接受以下处理:4mg·kg 的 MLX 和 1 或 4mg·kg 的 CEMNPs。在给药后 48 小时内采集血浆样本,并通过反相(C)高效液相色谱法(HPLC)定量 MLX 的浓度。应用非房室分析来确定药代动力学变量。口服给药后,CEMNPs 的 C 最大浓度(C)在 4 小时达到,而 MLX 在 6 小时达到。1mg·kg 的 CEMNPs 的 AUC(从 0 到无穷大的血浆 MLX 浓度-时间曲线下面积)、半衰期(t)和平均驻留时间(MRT)分别比 4mg·kg 的 MLX 高 1.4、2 和 1.8 倍。与 MLX 相比,制备的 CEMNPs 表现出更快的吸收和延长的释放,以及 MLX 的生物利用度显著提高,为开发具有更高生物利用度和更少副作用的药物铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/052f/9658985/5b3eb75efa3a/molecules-27-07312-g001.jpg

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