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  • Title: Enhancing effect of chitosan on nasal absorption of salmon calcitonin in rats: comparison with hydroxypropyl- and dimethyl-beta-cyclodextrins.
    Author: Sinswat P, Tengamnuay P.
    Journal: Int J Pharm; 2003 May 12; 257(1-2):15-22. PubMed ID: 12711157.
    Abstract:
    Two types of chitosan, i.e. the free amine (CS J) and the glutamate salt (CS G), were evaluated for their enhancing effect on in vivo nasal absorption of salmon calcitonin (sCT) in rats. The results were subsequently compared with beta-cyclodextrins, one of the most commonly studied enhancers. Solutions containing sCT and chitosan (0-1.25% w/v) in isotonic phosphate buffers (IPB; pH 3.0-6.0) were nasally administered at the dose of 10 IU/kg. The plasma calcium lowering effect in each sCT-treated rat was determined by calculating the total percent decrease in plasma calcium (%D). CS J showed an increase in %D as the solution pH was decreased in accordance with the increased ionization and hydration of the free amine chitosan at the more acidic pH. However, CS G showed an increase in %D with increasing pH, with maximum hypocalcemic effect observed at pH 6.0. At their optimal pH (4.0 for CS J and 6.0 for CS G), the absorption enhancing effect of both chitosans was concentration dependent from 0.25 to 1.0% and leveled off at 1.25%. Using specific RIA, the absolute bioavailability of sCT after comparison with i.v. administration was determined to be 2.45, 1.91, and 1.22% for 1% CS J, 5% dimethyl-beta-cyclodextrin (DM-beta-CD) and control group (intranasal (in) sCT alone), respectively. Although the absolute nasal bioavailability seemed to be low when compared to the i.v. administration, the inclusion of 1% CS J resulted in two-fold increase in the AUC(0-180) of plasma sCT relative to that of the control group. Addition of 5% DM-beta-CD also led to 1.56-fold increase in absorption over the control group. All the enhancers showed significant absorption enhancement (P<0.05) with the highest effect observed with CS J. In conclusion, cationic polymer chitosan may have promising potential as a safe and effective nasal absorption enhancer of sCT.
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