title: In vitro cell culture evaluation and in vivo efficacy of amphiphilic chitosan for oral insulin delivery.
abstract: The overall goal of this paper was to enhance the bioavailability of orally delivered insulin. A mucoadhesive amphiphilic chitosan derivative, lauroyl sulphated chitosan (LSCS) was used as the oral carrier for insulin. Trans epithelial electrical resistance experiment was performed on Caco-2 cell monolayers and observed a reduction of TEER after the incubation with the particles. The insulin transport experiment was done with excised rat intestinal tissue using an Ussing chamber and observed an enhanced transport of insulin due to the effect of LSCS. Following oral administration of FITC-insulin loaded LSCS in SD rats; the qualitative biodistribution of the administered drug was investigated using a fluorescence microscopy. The results showed the time dependent distribution of insulin through gastro intestinal tract (GIT). The efficacy of insulin-loaded LSCS sub micro particles (LSCS-ins) was investigated in diabetic rats by measuring the blood glucose level and found to be an effective reduction of the blood glucose level after oral administration of LSCS-ins. The pharmacological availability was found to be 2.5-fold and had a longer pharmacological activity compared with that of native insulin via oral and subcutaneous (sc) routes. The enhanced oral bioavailability of insulin may be associated with a higher release rate in the intestinal juice, enhanced absorption by improved permeability and increased residence time in the intestinal cavity. Thus, encapsulating insulin in LSCS matrix is a promising carrier for sustained and controlled drug delivery with improved bioavailability of insulin for diabetic patients.
authors.affiliation: Division of Biosurface Technology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram 695012, India.
authors.forename: R
authors.initials: R
authors.lastname: Shelma
authors.forename: Chandra P
authors.initials: CP
authors.lastname: Sharma
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D018938:Caco-2 Cells; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D003911:Dextrans; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology; D016503:Drug Delivery Systems; D017097:Electric Impedance; D004847:Epithelial Cells / Q000187:drug effects; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D005452:Fluoresceins; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008856:Microscopy, Fluorescence; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013501:Surface-Active Agents / Q000737:chemistry*; D014018:Tissue Distribution / Q000187:drug effects; D016896:Treatment Outcome; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D003911:Dextrans; D005452:Fluoresceins; D007328:Insulin; D013501:Surface-Active Agents; D062826:Zonula Occludens-1 Protein; C480355:chitosan sulfate; C052526:fluorescein-dextran; D048271:Chitosan; D016650:Fluorescein-5-isothiocyanate