Preparation of desmopressin-containing liposomes for intranasal delivery

The loading and leakage characteristics of the desmopressin-containing lipo somes and the effect of liposomes on the nasal mucosa permeation and antidi uresis of desmopressin were investigated. Higher loading efficiency of desm opressin for positively charged liposomes than negatively charged liposomes was obtained, and neutral liposomes resulted in a similar loading efficien cy as that of positively charged liposomes. Greater leakage of desmopressin from negatively charged liposomes than from positively charged and neutral liposomes was shown. The increase of permeability of desmopressin through the nasal mucosa indicated positively charged liposomes>negatively charged liposomes>solution. It was suggested that the enhanced contact time of posi tively charged liposomes with negatively charged nasal mucosa led to a high local desmopressin concentration on the penetration site to promote an eff ective penetration of desmopressin through the nasal mucosa. The desmopress in antidiuresis result after intranasal administration was in good agreemen t with the permeability result in the order of positively charged liposomes >negatively charged liposomes>solution. One of the mechanisms for the expla nation of the best result on the enhancement of antidiuresis for positively charged liposomes may be the bioadhesive effect of the liposomes on the ne gatively charged nasal mucosa. (C) 2001 Elsevier Science B.V. All rights re served.