Solid lipid nanoparticles (SLNs) are one of the most promising nanocarriers to increase the oral absorption of drugs with poor solubility and low permeability. However, the absorption mechanism of SLNs remains incomplete and thus requires further careful consideration. In this study, positively charged chitosan (CS) modified SLNs or hydroxypropyl trimethylammonium chloride chitosan (HACC) modified SLNs were designed and their absorption mechanisms were fully clarified to improve the oral absorption of docetaxel (DTX). The HACC-DTX-SLNs showed the highest cellular uptake in Caco-2 cell monolayer; the transport efficacy in the follicle-associated epithelium cell monolayer was higher than that in the Caco-2 cell monolayer. The CS- or HACC-modified SLNs could reversibly regulate the transepithelial electrical resistance and the expressions of tight junction (TJ) associated proteins, such as claudin-1, occludin, and zonula occludens-1. The uptake of HACC-DTX-SLNs through Peyer's patches was higher than that of the normal tissue of the small intestine in rats. The enhanced absorption mechanisms of HACC-DTX-SLNs were mainly related to the caveola-mediated endocytosis, M cell phagocytosis, and reversible TJ opening.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81373333, 81311140267]; Suzhou Science and Technology Bureau [SYS201204]; Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions; Applied Basic Research Program
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2015]版：
大类|2 区医学
小类|2 区医学：研究与实验2 区药学
最新[2023]版：
大类|2 区医学
小类|2 区药学3 区医学：研究与实验
JCR分区：
出版当年[2014]版：
Q1MEDICINE, RESEARCH & EXPERIMENTALQ1PHARMACOLOGY & PHARMACY
最新[2023]版：
Q1PHARMACOLOGY & PHARMACYQ2MEDICINE, RESEARCH & EXPERIMENTAL
第一作者机构：[1]Soochow Univ, Coll Pharmaceut Sci, Suzhou, Peoples R China[2]Jiaxing Univ, Coll Med, Jiaxing, Peoples R China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Shi Li-Li,Xie Hongjuan,Lu Jia,et al.Positively Charged Surface-Modified Solid Lipid Nanoparticles Promote the Intestinal Transport of Docetaxel through Multifunctional Mechanisms in Rats[J].MOLECULAR PHARMACEUTICS.2016,13(8):2667-2676.doi:10.1021/acs.molpharmaceut.6b00226.
APA：
Shi, Li-Li,Xie, Hongjuan,Lu, Jia,Cao, Yue,Liu, Jiang-Yan...&Cao, Qing-Ri.(2016).Positively Charged Surface-Modified Solid Lipid Nanoparticles Promote the Intestinal Transport of Docetaxel through Multifunctional Mechanisms in Rats.MOLECULAR PHARMACEUTICS,13,(8)
MLA：
Shi, Li-Li,et al."Positively Charged Surface-Modified Solid Lipid Nanoparticles Promote the Intestinal Transport of Docetaxel through Multifunctional Mechanisms in Rats".MOLECULAR PHARMACEUTICS 13..8(2016):2667-2676
