Chitosan nanocapsules as carriers for oral peptide delivery: effect of chitosan molecular weight and type of salt on the in vitro behaviour and in vivo effectiveness.
We have recently reported preliminary data showing the efficacy of chitosan nanocapsules as carriers for oral peptide delivery. In the present work, our aim was to investigate the influence of some chitosan properties, such as the molecular weight and type of salt, on the interaction of these nanocapsules with the Caco-2 cells and also on their in vivo effectiveness. Chitosan nanocapsules were prepared by the solvent displacement technique using high (450 kDa) and medium (160 kDa) molecular weight chitosan glutamate as well as high molecular weight chitosan hydrochloride (270 kDa). The results indicated that the size of the nanocapsules was dependent on the chitosan molecular weight, whereas the zeta potential and the association efficiency of salmon calcitonin were not affected by the chitosan properties. Upon incubation with the Caco-2 cells, chitosan nanocapsules exhibited a dose-dependent cellular viability, which was hardly affected by, either the chitosan molecular weight or, the type of salt. In addition, it was observed that the transepithelial electrical resistance of the Caco-2 monolayer was not significantly modified upon their exposure to chitosan nanocapsules. The results of the in vivo studies, following oral administration to rats, indicated that chitosan nanocapsules were able to reduce significantly the serum calcium levels, and to prolong this reduction for at least 24 hours, irrespective of the type of chitosan salt and molecular weight of chitosan. Consequently, the performance of chitosan nanocapsules as oral carriers for salmon calcitonin was not affected by the characteristics of chitosan.
Prego
C
C
Department of Pharmaceutical Technology, University of Santiago de Compostela, Campus Sur, 15782 Santiago de Compostela, Spain.
Torres
D
D
Alonso
M J
MJ
D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D002116:Calcitonin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002118:Calcium / Q000097:blood; D002214:Capsules / Q000008:administration & dosage / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects*; D048271:Chitosan / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D008297:Male; D008422:Materials Testing; D008970:Molecular Weight; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D036361:Peptide Hormones / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012492:Salts / Q000737:chemistry
D002214:Capsules; D004337:Drug Carriers; D036361:Peptide Hormones; D012492:Salts; D002116:Calcitonin; D048271:Chitosan; D002118:Calcium