The relationship between the rigidity of the liposomal membrane and the absorption of insulin after nasal administration of liposomes modified with an enhancer containing insulin in rabbits.
The relationship between the rigidity of the liposomal membrane and the absorption of insulin after nasal administration of liposomes modified with an enhancer containing insulin was investigated for the nasal delivery of peptide drugs in rabbits. The rigid liposomal membrane makes liposomes stable, protecting insulin from enzymatic degradation. Soybean-derived sterol (SS) or its sterylglucoside (SG) was used as an enhancer. Dipalmitoylphosphatidylcholine (DPPC) liposomes modified with SG had increased fluidity of the hydrophobic group of the liposome bilayer compared with the liposomes modified with cholesterol (Ch) or SS, as shown by measurements of the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5,-hexatriene (DPH); however, the fluidity of the polar group of the liposome bilayer was decreased according to measurements of steady-state fluorescence anisotropy of dansylhexadecylamine (DSHA) at 37 degrees C. These findings suggest that the fluidity of the hydrophobic group of the liposome bilayer is responsible for the increase of liposomal leakage and instability of the liposomes. When insulin was administered nasally to rabbits as a solution, no hypoglycemic effect was observed. The administration of insulin contained in DPPC/SG (7/4, mole) liposomes with high fluidity caused a high glucose reduction of long duration (8 hr). DPPC/SS and DPPC/Ch (7/4) liposomes with low fluidity caused low glucose reductions. These results demonstrated that liposomes modified with SG can be useful as carriers of insulin administered nasally.
Muramatsu
K
K
Department of Pharmaceutics, Hoshi University, Tokyo, Japan.
Maitani
Y
Y
Takayama
K
K
Nagai
T
T
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000008:administration & dosage / Q000737:chemistry; D000042:Absorption; D000281:Administration, Intranasal; D000818:Animals; D002782:Cholestenes / Q000008:administration & dosage / Q000737:chemistry; D002784:Cholesterol / Q000008:administration & dosage / Q000737:chemistry; D004161:Diphenylhexatriene / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers; D005260:Female; D005454:Fluorescence Polarization; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008081:Liposomes / Q000737:chemistry*; D008560:Membrane Fluidity; D009297:Nasal Mucosa / Q000378:metabolism; D010840:Phytosterols / Q000008:administration & dosage / Q000737:chemistry; D011817:Rabbits
D002782:Cholestenes; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D008081:Liposomes; D010840:Phytosterols; C096056:soy derived sterylglucoside mixture; D004161:Diphenylhexatriene; D015060:1,2-Dipalmitoylphosphatidylcholine; D002784:Cholesterol; C033580:soysterol