title: Positively Charged Surface-Modified Solid Lipid Nanoparticles Promote the Intestinal Transport of Docetaxel through Multifunctional Mechanisms in Rats.
abstract: 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.
authors.affiliation: College of Pharmaceutical Sciences, Soochow University , Suzhou, People's Republic of China.|College of Medicine, Jiaxing University , Jiaxing, People's Republic of China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Shi
authors.affiliation: Tongren Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, People's Republic of China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Xie
authors.affiliation: College of Pharmaceutical Sciences, Soochow University , Suzhou, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Lu
authors.affiliation: College of Pharmaceutical Sciences, Soochow University , Suzhou, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cao
authors.affiliation: College of Pharmaceutical Sciences, Soochow University , Suzhou, People's Republic of China.
authors.forename: Jiang-Yan
authors.initials: JY
authors.lastname: Liu
authors.affiliation: College of Pharmaceutical Sciences, Soochow University , Suzhou, People's Republic of China.
authors.forename: Xiao-Xue
authors.initials: XX
authors.lastname: Zhang
authors.affiliation: College of Pharmaceutical Sciences, Soochow University , Suzhou, People's Republic of China.
authors.forename: Hongjian
authors.initials: H
authors.lastname: Zhang
authors.affiliation: College of Pharmaceutical Sciences, Soochow University , Suzhou, People's Republic of China.
authors.forename: Jing-Hao
authors.initials: JH
authors.lastname: Cui
authors.affiliation: College of Pharmaceutical Sciences, Soochow University , Suzhou, People's Republic of China.
authors.forename: Qing-Ri
authors.initials: QR
authors.lastname: Cao
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D048271:Chitosan / Q000737:chemistry; D000077143:Docetaxel; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry*; D008297:Male; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043823:Taxoids / Q000378:metabolism*
chemical_list: D008055:Lipids; D043823:Taxoids; D000077143:Docetaxel; D048271:Chitosan
keywords: chitosan; docetaxel; hydroxypropyl trimethylammonium chloride chitosan; oral absorption mechanism; solid lipid nanoparticle