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Effect of chitosan and thiolated chitosan coating on the inhibition behaviour of PIBCA nanoparticles against intestinal metallopeptidases

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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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Acknowledgements

Authors want to thank Dr K. Broadley from Henkel Biomedical (Dublin, Ireland) for his kindness in providing the isobutylcyanoacrylate monomer. Authors also want to thank the Department of Organic Chemistry (Biocis UMR CNRS 8076), Faculty of Pharmacy, University Paris-XI (Chatenay-Malabry, France) for their help in the synthesis of 2-iminothiolane and the “Service central d’analyse du CNRS” (Vernaison, France) for the elemental analysis of thiolated polymers.

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Authors and Affiliations

  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

    Irene Bravo-Osuna, Christine Vauthier, Alessandra Farabollini, Gioconda Millotti & Gilles Ponchel

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  1. Irene Bravo-Osuna
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  2. Christine Vauthier
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  3. Alessandra Farabollini
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  4. Gioconda Millotti
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  5. Gilles Ponchel
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Correspondence to Gilles Ponchel.

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Bravo-Osuna, I., Vauthier, C., Farabollini, A. et al. Effect of chitosan and thiolated chitosan coating on the inhibition behaviour of PIBCA nanoparticles against intestinal metallopeptidases. J Nanopart Res 10, 1293–1301 (2008). https://doi.org/10.1007/s11051-008-9364-5

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  • DOI: https://doi.org/10.1007/s11051-008-9364-5

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