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纳米医学I:紫杉醇负载的聚(ε-己内酯)、聚(DL-丙交酯-共-乙交酯)和聚(DL-乳酸)基质纳米颗粒在Wistar大鼠体内外的评价

Nanomedicine I: In vitro and in vivo evaluation of paclitaxel loaded poly-(ε-caprolactone), poly (DL-lactide-co-glycolide) and poly (DL-lactic acid) matrix nanoparticles in wistar rats.

作者信息

VasanthaKumar Sekar, Ahamed Haja Nazeer, Saha Ranendra N

机构信息

Industrial Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science (BITS-Pilani), Pilani, Rajasthan, India,

出版信息

Eur J Drug Metab Pharmacokinet. 2015 Jun;40(2):137-61. doi: 10.1007/s13318-014-0189-6. Epub 2014 Mar 27.

DOI:10.1007/s13318-014-0189-6
PMID:24671895
Abstract

Progress in nanoscience and nanotechnology laid foundation for nanotherapy-based approach in cancer drug delivery for improved therapy and quality of life. The prepared polymeric nanoparticles (PNPs), PCL, PLGA and PLA NPs help in delivering paclitaxel (TAX) in vivo by avoiding the use of unsafe excipient, Cremophore EL. The classy microscopic examination SEM, TEM and AFM analysis revealed the spherical and smooth structure of the NPs as well as their homogeneous solid matrix without any amorphous arrangements. The FTIR analysis of PNPs exposed that there was no chemical interaction between polymer, stabilizer and TAX. The (1)H NMR and XRD analyses illustrate molecular dispersion of TAX in the polymeric matrix and no evidence was observed for the presence of crystalline TAX. The outcome of in vivo acute toxicity study endorses residual solvent free PNPs. The PNPs demonstrate excellent control in delivering TAX up to 48 h with best fitted to First-order, Baker-Lonsdale, Higuchi and Korsmeyer-Peppas model. The log plasma concentration-time profile shows that the prepared PNPs were safe and have much less side-effects. The pharmacokinetic study results illustrate increase in mean residence time as result of long circulating nature of the prepared nanoparticles, which helps them to reach target area. The estimated pharmacokinetic parameters AUC0-∞ (ng h)/mL, AUMC0-∞ (ng h(2))/mL, C max (ng/mL), t 1/2 (h), MRT (h), Cl (L/h/kg), V ss (L/kg) and V z (L/kg) shows improved therapeutic efficacy when compared with TAX solution.

摘要

纳米科学和纳米技术的进展为基于纳米疗法的癌症药物递送方法奠定了基础,以改善治疗效果和生活质量。制备的聚合物纳米颗粒(PNPs)、聚己内酯(PCL)、聚乳酸-羟基乙酸共聚物(PLGA)和聚乳酸(PLA)纳米颗粒通过避免使用不安全的辅料聚氧乙烯蓖麻油(Cremophore EL),有助于在体内递送紫杉醇(TAX)。经典的显微镜检查扫描电子显微镜(SEM)、透射电子显微镜(TEM)和原子力显微镜(AFM)分析揭示了纳米颗粒的球形和光滑结构以及它们均匀的固体基质,没有任何无定形排列。PNPs的傅里叶变换红外光谱(FTIR)分析表明聚合物、稳定剂和TAX之间没有化学相互作用。氢核磁共振(¹H NMR)和X射线衍射(XRD)分析表明TAX在聚合物基质中呈分子分散状态,未观察到结晶TAX存在的证据。体内急性毒性研究结果支持无残留溶剂的PNPs。PNPs在长达48小时的时间内展示了出色的TAX递送控制能力,最符合一级、贝克-朗斯代尔、 Higuchi和考斯迈尔-佩帕斯模型。对数血浆浓度-时间曲线表明,制备的PNPs是安全的,副作用小得多。药代动力学研究结果表明,由于制备的纳米颗粒具有长循环特性,平均驻留时间增加,这有助于它们到达靶区域。与TAX溶液相比,估计的药代动力学参数曲线下面积(AUC0-∞)(ng h)/mL、一阶矩曲线下面积(AUMC0-∞)(ng h²)/mL、最大血药浓度(C max)(ng/mL)、半衰期(t 1/2)(h)、平均驻留时间(MRT)(h)、清除率(Cl)(L/h/kg)、稳态分布容积(V ss)(L/kg)和中央室分布容积(V z)(L/kg)显示出更好的治疗效果。

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