The objective of this work was to explore the potential of ultraflexible liposomes as carriers for improving the absorption of salmon calcitonin (sCT) through intranasal administration. The average diameters of positively charged ultraflexible liposomes ranged from about 73 to 99 nm, while those of negatively charged ones were 114 and 157.6 nm, respectively. The content of sodium deoxycholate in liposomes markedly affected the size and encapsulated efficiency of liposomes. The absorption of sCT through intranasal administration was evaluated by hypocalcemic efficacy in rats. The total Ca decrease D% of sCT-loaded ultraflexible liposomes with positive and negative charges were significantly bigger than that of sCT solution, while there was no significant difference in the hypocalcemic efficacy between plain liposome and sCT solution. Unexpectedly, the hypocalcemic efficacy of sCT-loaded ultraflexible liposomes with positive charges was not significantly better than those with negative charges. The decrease rate and extent of the serum calcium level for subcutaneous injection of sCT solution were almost equivalent to those for intranasal administration of negatively and positively charged ultraflexible liposomes within the first 2 h, indicating that the ultraflexible liposomes could quickly enhance the penetration of the drug during their residence in the nasal cavity. The results of the toxicity of sCT-loaded ultraflexible liposomes to nasal mucosa demonstrated that the ultraflexible liposomes exerted slight toxicity on the nasal mucosa. On an overall evaluation, the ultraflexible liposomes may be a useful vehicle for intranasal delivery of sCT. (C) 2009 Elsevier Inc. All rights reserved.