Effect of chitosan and thiolated chitosan coating on the inhibition behaviour of PIBCA nanoparticles against intestinal metallopeptidases |
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Authors: | Irene Bravo-Osuna Christine Vauthier Alessandra Farabollini Gioconda Millotti Gilles Ponchel |
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Institution: | (1) Laboratoire de Physicochimie, Faculté de Pharmacie, Pharmacotechnie et Biopharmacie, UMR CNRS 8612, Université Paris Sud, 5, Rue J.B. Clément, 92296 Chatenay-Malabry, France |
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Abstract: | Surface modified nanoparticles composed of poly(isobutylcyanoacrylate) (PIBCA) cores surrounded by a chitosan and thiolated
chitosan gel layer were prepared and characterized in previous works. The presence of such biopolymers on the nanoparticle
surface conferred those nanosystems interesting characteristics that might partially overcome the gastrointestinal enzymatic
barrier, improving the oral administration of pharmacologically active peptides. In the present work, the antiprotease behaviour
of this family of core–shell nanoparticles was in vitro tested against two model metallopeptidases present in the gastrointestinal
tract (GIT): Carboxypeptidase A -CP A- (luminal protease) and Leucine Aminopeptidase M -LAP M- (membrane protease). As previous
step, the zinc-binding capacity of these nanoparticles was evaluated. Interestingly, an improvement of both the zinc-binding
capacity and the antiprotease effect of chitosan was observed when the biopolymers (chitosan and thiolated chitosan) were
used as coating component of the core–shell nanoparticles, in comparison with their behaviour in solution, thanks to the different
biopolymer chains rearrangement. The presence of amino, hydroxyl and thiol groups on the nanoparticle surface promoted zinc
binding and hence the inhibition of the metallopeptidases analysed. On the contrary, the occurrence of a cross-linked structure
in the gel layer surrounding the PIBCA cores of thiolated formulations, due to the formation of interchain and intrachain
disulphide bonds, partially limited the inhibition of the proteases. The low accessibility of cations to the active groups
of the cross-linked polymeric shell was postulated as a possible explanation of this behaviour. Results obtained in this work
make this family of surface-modified nanocarriers promising candidates for the successfull administration of pharmacologically
active peptides and proteins by the oral route. |
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Keywords: | Core– shell nanoparticles Chitosan Thiolated chitosan Poly(isobutylcyanoacrylate) Zinc-binding capacity Intestinal metallopeptidases Nanomedicine |
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