Design, characterisation, and bioefficiency of insulin–chitosan nanoparticles after stabilisation by freeze-drying or cross-linking

Design, characterisation, and bioefficiency of insulin–chitosan nanoparticles after stabilisation by freeze-drying or cross-linking

[Display omitted] Insulin delivery by oral route would be ideal, but has no effect, due to the harsh conditions of the gastrointestinal tract. Protection of insulin using encapsulation in self-assembled particles is a promising approach. However, the lack of stability of this kind of particles in bi...

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Bibliographic Details
Published in:International journal of pharmaceutics Vol. 491; no. 1-2; pp. 402 - 408
Main Authors: Diop, M., Auberval, N., Viciglio, A., Langlois, A., Bietiger, W., Mura, C., Peronet, C., Bekel, A., Julien David, D., Zhao, M., Pinget, M., Jeandidier, N., Vauthier, C., Marchioni, E., Frere, Y., Sigrist, S.
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01-08-2015
Subjects:
Animals
Blood Glucose - metabolism
Caco-2 Cells
Chemistry, Pharmaceutical
Chitosan
Chitosan - chemistry
Complex coacervation
Cross-Linking Reagents
Drug Delivery Systems
Drug Design
Drug Stability
Excipients
Freeze Drying
Humans
Insulin
Insulin - administration & dosage
Insulin - chemistry
Insulin - pharmacology
Male
Mucus - metabolism
Nanoparticles
Nanoparticles - chemistry
Oral administration
Rats
Rats, Wistar
Nanoparticles
Complex coacervation
Chitosan
Insulin
Oral administration
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Summary:[Display omitted] Insulin delivery by oral route would be ideal, but has no effect, due to the harsh conditions of the gastrointestinal tract. Protection of insulin using encapsulation in self-assembled particles is a promising approach. However, the lack of stability of this kind of particles in biological environments induces a low bioavailability of encapsulated insulin after oral administration. The objective of this work was to evaluate the effect of two stabilisation strategies alone or combined, freeze-drying and cross-linking, on insulin-loaded chitosan NPs, and to determine their bioefficiency in vitro and in vivo. NPs were prepared by complex coacervation between insulin and chitosan, stabilised either by cross linking with sodium tripolyphosphate solution (TPP), by freeze-drying or both treatments. In vitro bioefficiency NP uptake was evaluated by flow cytometry on epithelial models (Caco-2/RevHT29MTX (mucus secreting cells)). In vivo, NPs were injected via catheter in the peritoneum or duodenum on insulinopenic rats. Freeze-drying increased in size and charge (+15% vs control 412±7nm; +36±0.3mV) in comparison with cross linking which decreased NP size (−25%) without impacting the NP charge. When combined the consecutive treatments reduced NPs size and increased charges as compared to standard level. Freeze drying is necessary to prevent the destruction of NP in intestinal environment in comparison with no freeze dryed one where 60% of NP were destroyed after 2h. Additionally freeze drying combined with cross linking treatments improved bioefficiency of NP with uptake in cell increased when mucus is present. Combination of both treatment showed a protection of insulin in vivo, with a reduction of glycemia when NPs were administrated. This work showed that the combination of freeze drying and cross linking treatment is necessary to stabilize (freeze-drying) and increase bioefficiency (cross-linking) of self assembled NP in the delivery of insulin in vitro and in vivo.
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ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2015.05.065