In vivo evaluation of an oral salmon calcitonin-delivery system based on a thiolated chitosan carrier matrix.
OBJECTIVE
To develop and evaluate an oral delivery system for salmon calcitonin.


METHODS
2-Iminothiolane was covalently bound to chitosan in order to improve the mucoadhesive and cohesive properties of the polymer. The resulting chitosan-TBA conjugate (chitosan-4-thiobutylamidine conjugate) was homogenized with salmon calcitonin. mannitol, and a chitosan-Bowman-Birk inhibitor conjugate and a chitosan-elastatinal conjugate (6.75 + 0.25 + 1 + 1 + 1). Optionally 0.5% (m/m) reduced glutathione. used as permeation mediator, was added. Each mixture was compressed to 2 mg microtablets and enteric coated with a polymethacrylate. Biofeedback studies were performed in rats by oral administration of the delivery system and determination of the decrease in plasma calcium level as a function of time.


RESULTS
Test formulations led to a significant (p < 0.005) decrease in the plasma calcium level of the dosed animals in comparison to control tablets being based on unmodified chitosan. The addition of glutathione in the tablets led to a further improvement in the oral bioavailability of salmon calcitonin with an earlier onset of action and a decrease in the calcium level of about 10% for at least 10 h.


CONCLUSIONS
The combination of mucoadhesive thiolated chitosan, chitosan-enzyme-inhibitor conjugates and the permeation mediator glutathione seems to represent a promising strategy for the oral delivery of salmon calcitonin.
Guggi
Davide
D
Institute of Pharmaceutical Technology and Biopharmaceutics, Center of Pharmacy, University of Vienna, Althanstr. 14, A-1090 Vienna, Austria.
Kast
Constantia E
CE
Bernkop-Schnürch
Andreas
A
D000818:Animals; D001682:Biological Availability; D002116:Calcitonin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry*; D048271:Chitosan; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005079:Excipients; D005978:Glutathione / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013607:Tablets; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000737:chemistry / Q000494:pharmacology
D004337:Drug Carriers; D005079:Excipients; D013607:Tablets; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D002686:Chitin; C028815:salmon calcitonin; D002116:Calcitonin; D048271:Chitosan; D005978:Glutathione