Mucoadhesive properties of carbopol or chitosan-coated liposomes and their effectiveness in the oral administration of calcitonin to rats

Mucoadhesive liposomes were prepared by coating multilamellar liposomes with Carbopol (CP) in a similar manner to that used in the preparation of chitosan-coated liposomes (CS-Lip) previously reported [Takeuchi et al., Chem. Pharm. Bull. 42 (1994) 1954-1956; Pharm. Res. 13 (1996) 896-901]. The positively charged liposomes containing dipalmitoylphos-phatidylcholine (DPPC) and stearylamine at an optimum formulation ratio (40:1) could be coated with CP without aggregation of the liposomal particles during the coating process. The mucoadhesive properties of both the resultant polymer-coated liposomes (CP-Lip and CS-Lip) and the positively or negatively charged noncoated liposomes (Non-Lip) were evaluated using the rat intestine. The order was CS-Lipgreater than or equal to CP-Lip>positively charged Non-Lip>negatively charged Non-Lip. The adhesive property of CP-Lip decreased on increasing pH of the dispersing medium from pH 5.0 to 7.4, probably owing to the electric repulsion between CP-Lip and the mucus layer. The effectiveness of the liposomal formulations in oral administration of calcitonin was evaluated by measuring the change in the blood calcium concentration of rats. Administration of CP-Lip and CS-Lip containing calcitonin showed an enhanced and prolonged reduction in blood calcium concentration. The overall pharmacological effect of CP- and CS-Lips evaluated by means of the area under the plasma calcium concentration curve was 2.4 and 2.8 times higher than that of negatively and positively charged Non-Lips, respectively. (C) 2002 Elsevier Science B.V. All rights reserved.