Polyarginine Nanocapsules as a Potential Oral Peptide Delivery Carrier

被引:28
|
作者
Lollo, Giovanna [1 ,2 ,4 ]
Gonzalez-Paredes, Ana [1 ,2 ]
Garcia-Fuentes, Marcos [1 ,2 ]
Calvo, Pilar [3 ]
Torres, Dolores [1 ]
Jose Alonso, Maria [1 ,2 ]
机构
[1] Univ Santiago de Compostela, Dept Pharmaceut & Pharmaceut Technol, Sch Pharm, Campus Vida, Santiago De Compostela 15782, Spain
[2] Univ Santiago de Compostela, Ctr Res Mol Med & Chron Dis CIMUS, Campus Vida, Santiago De Compostela 15782, Spain
[3] PharmaMar SA, Madrid 28770, Spain
[4] Univ Claude Bernard Lyon 1, Univ Lyon, CNRS, LAGEP UMR 5007, 43 Blvd 11 Novembre 1918, F-69100 Villeurbanne, France
关键词
nanotechnology; nanocapsules; colloid; biodegradable polymers; biomaterials; cancer; Caco-2; cells; oral drug delivery; oral absorption; surfactants; POLY-L-ARGININE; CELL-PENETRATING PEPTIDES; TIGHT JUNCTION PROTEINS; PARACELLULAR PERMEABILITY; CHITOSAN NANOCAPSULES; MOLECULAR-WEIGHT; ABSORPTION; MECHANISM; INTERNALIZATION; NANOPARTICLES;
D O I
10.1016/j.xphs.2016.09.029
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
We have previously reported the development of novel nanocapsules made of polyarginine ( PArg) specifically designed for the delivery of small anticancer drugs into cells. Our goal, in this work, has been to investigate the potential of these nanocarriers for oral delivery of peptide anticancer drugs. To reach this objective, we chose the antitumoral peptide, elisidepsin, and evaluated the characteristics of the PArg nanocapsules in terms of drug loading capacity, stability in simulated intestinal fluids, and ability to interact with the intestinal epithelium both in vitro ( Caco-2 model cell line) and in vivo. Our results suggest that elisidepsin can be effectively loaded into the nanocapsules by adjusting the formulation parameters, using a solvent displacement technique. The resulting nanocapsules were stable upon incubation in simulated intestinal fluids and had the ability to reduce, in a transient manner, the transepithelial electrical resistance of the Caco-2 cell monolayer. Confocal images also revealed that PArg nanocapsules were internalized by the monolayer without evident signs of cytotoxicity. Finally, the in vivo fluorescent imaging study illustrates the retention of the nanocapsules in the gastrointestinal tract upon oral administration. Overall, the results underline the potential interest of PArg nanocapsules as carriers for the oral administration of peptide drugs. (C) 2017 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:611 / 618
页数:8
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