Efficacy and mechanistic studies of chitosan as nasal absorption enhancer of peptide drugs
1999
Phakphum Teng-amnuai | Atchariya Sailasut | Kanphimol Ritthidet (Chulalongkorn Univ., Bangkok (Thailand). Faculty of Veterinary Science)
Two chitosans were subsequently studied for their possible membrane damaging effects based on measurements of released mucosal components and histological evaluation. Results. At 0.5 percent w/v, both CS J and CS G were effective in enhancing the nasal absorption of [D-Ary sup(2)]-Kyotorphin. The enhancing effect of CS J was significatly greater at pH 4.0 than at pH 5.0 and 6.0 (p0.05) in accordace with the nature of the free amine chitosan to swell and dissolve better in the more acidic conditions. However, there were no significant differences in the adjuvant activity of the soluble acid salt CS G at pH 4.0, 5.0 and 6.0 (p0.05). CS J and G were subsequently selected for further studies at their optimum pH (4.0 for CS J and 6.0 for CS G). At only 0.02 percent w/v, their enhancing effects were already significant and similar to that of 5 percent w/v hydroxypropyl-Beta-cyclodextrin (HP-Beta-CD). Determination of the protein and phosphrus content in the nasal perfusates indicated that the two chitosans, at 0.1 percent w/v, caused minimal release of these substances similar to that of HP-Beta-CD (p0.05). However, they were much smaller than the previously reported values for dimethyl-Beta-cyclodextrin, an effective enhancer which, at 5 percent w/v, gave the protein an total phosphorus release rates about 4-7 folds higher than chitosans. Conclusions. Both CS J and CS G were effective in enhancing nasal absorption of [D-Ary sup(2)]-Kyotorphin. Results from the mucosal component release, morphogical and reversibility studies indicated that chitosans may have a potential for further studies as a safe effective nasal absorption enhancer.
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