Cysteine-Functionalized Nanostructured Lipid Carriers for Oral Delivery of Docetaxel: A Permeability and Pharmacokinetic Study
Molecular Pharmaceutics, ISSN: 1543-8392, Vol: 12, Issue: 7, Page: 2384-2395
2015
- 75Citations
- 83Captures
- 1Mentions
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- Citations75
- Citation Indexes75
- 75
- CrossRef52
- Captures83
- Readers83
- 83
- Mentions1
- News Mentions1
- News1
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Cysteine-Functionalized Nanostructured Lipid Carriers for Oral Delivery of Docetaxel: A Permeability and Pharmacokinetic Study.
Authors: Guihua Fang, Bo Tang, Yanhui Chao, Helin Xu, Jingxin Gou, Yu Zhang, Hui Xu, Xing Tang PMID: 25974386 DOI: 10.1021/acs.molpharmaceut.5b00081 Publication Type: Research Support,
Article Description
Here we report the development and evaluation of cysteine-modified nanostructured lipid carriers (NLCs) for oral delivery of docetaxel (DTX). The NLCs ensure high encapsulation efficiency of docetaxel, while the cysteine bound the NLCs with PEG2000-monostearate (PEG2000-MSA) as a linker, and allowed a specific interaction with mucin of the intestinal mucus layer and facilitated the intestinal transport of docetaxel. The cysteine-modified NLCs (cNLCs) had a small particle size (<100 nm) and a negative zeta potential (-13.72 ± 0.07 mV), which was lower than that of the unmodified NLCs (uNLCs) (-6.39 ± 0.07 mV). This correlates well with the location of the cysteine group on the surface of the NLCs obtained by X-ray photoelectron spectroscopy (XPS). The cNLCs significantly improved the mucoadhesion properties compared with uNLCs. The intestinal absorption of cNLCs in total intestinal segments was greatly improved in comparison with uNLCs and docetaxel solution (DTX-Sol), and the in vivo imaging system captured pictures also showed not only increased intestinal absorption but also improved accumulation in blood. The cNLCs could be absorbed into the enterocytes via both endocytosis and passive transport. The results of the in vivo pharmacokinetic study indicated that the AUC0-t of cNLCs (1533.00 ng/mL·h) was markedly increased 12.3-fold, and 1.64-fold compared with docetaxel solution and uNLCs, respectively. Overall, the cysteine modification makes nanostructured lipid carriers more suitable as nanocarriers for oral delivery of docetaxel. (Figure Presented).
Bibliographic Details
American Chemical Society (ACS)
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