Rationally designed hyaluronic acid-based nano-complexes for pentamidine delivery

被引:28
作者
Carton, Flavia [1 ,2 ]
Chevalier, Yves [1 ]
Nicoletti, Letizia [1 ,2 ]
Tarnowska, Malgorzata [1 ]
Stella, Barbara [3 ]
Arpicco, Silvia [3 ]
Malatesta, Manuela [2 ]
Jordheim, Lars Petter [4 ]
Briancon, Stephanie [1 ]
Lollo, Giovanna [1 ]
机构
[1] Univ Claude Bernard Lyon 1, Univ Lyon, CNRS, LAGEPP UMR 5007, 43 Bd 11 Novembre 1918, F-69622 Villeurbanne, France
[2] Univ Verona, Dept Neurosci Biomed & Movement Sci, Anat & Histol Sect, Str Grazie 8, Verona, Italy
[3] Univ Torino, Dept Drug Sci & Technol, Via P Giuria 9, Turin, Italy
[4] Univ Claude Bernard Lyon 1, Univ Lyon, Ctr Rech Cancerol Lyon, INSERM 1052,CNRS 5286,Ctr Leon Berard, F-69008 Lyon, France
关键词
Hyaluronic acid; Polyarginine; Pentamidine; Biomaterials; Drug delivery systems; DRUG; NANOPARTICLES; RELEASE; CANCER; POLYARGININE; NANOCAPSULES; FORMULATION; BEHAVIOR; SYSTEMS;
D O I
10.1016/j.ijpharm.2019.118526
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Nanoparticles of polymeric complexes made of hyaluronic acid and polyarginine were investigated for the encapsulation of the cationic hydrophilic drug pentamidine isethionate. The interaction between the anionic hyaluronic acid and the cationic pentamidine resulting in the formation of polyelectrolyte complexes was firstly studied. Then, nanoparticles made of hyaluronic acid and polyarginine loaded with pentamidine were developed. These drug delivery systems consist of a monodisperse population of negatively charged pentamidine-loaded nanoparticles with a high drug encapsulation rate (80%). Such high encapsulation efficiency coming from ion exchange was confirmed by measurements of the counterion isethionate released from pentamidine during nanoparticles formation. Besides, freeze-dried pentamidine-loaded nanoparticles kept their integrity after their reconstitution in water. In vitro studies on human lung (A549) and breast (MDA-MB-231) cancer cell lines showed that pentamidine-loaded nanoparticles were more cytotoxic in comparison to the free drug, suggesting an enhanced internalization of encapsulated drug by cancer cells.
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页数:11
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