Suitability of liposomal carriers for systemic delivery of risedronate using the pulmonary route.
OBJECTIVE
This study aims at testing the hypothesis that reversed phase evaporation liposomes (REVs) are suitable for systemic delivery of an anti-osteporotic drug (risedronate sodium (RS)) via pulmonary nebulization.


METHODS
RS REVs were prepared using phospholipids and cholesterol with or without stearylamine, and were characterized for morphology, entrapment efficiency (EE%), in vitro release, particle size and aerosolization behavior from an actively vibrating mesh nebulizer. RS accumulation in rat bones following intra-tracheal administration of the selected formulation was assessed using a radiolabelling-based technique, and histological examination of rat lung tissue was performed to assess its safety.


RESULTS
The EE% of RS REVs ranged from 8.8% to 58.96% depending on cholesterol molar ratio, phospholipid type and presence of stearylamine. RS REVs' particle size ranged from 2.15 to 3.61 µm and were spherical and moderately polydisperse. Nebulization of the selected formulation showed an aerosol output of 85%, a fine particle fraction of 70.75% and a predicted alveolar deposition of 30.39%. The amount of radiolabelled RS deposited in rat bones after pulmonary administration was 20%, while being considerably safe on lung tissues.


CONCLUSIONS
Cationic REVs is a promising carrier for systemic delivery of RS for treatment of bone resorptive diseases.
Faculty of Pharmacy, Ain Shams University, Pharmaceutics and Industrial Pharmacy , Cairo , Egypt and.
Maha
M
Nasr
Ismail
I
Taha
Rania M
RM
Hathout
D000280:Administration, Inhalation; D000336:Aerosols; D000588:Amines / Q000737:chemistry; D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D001842:Bone and Bones / Q000378:metabolism; D002784:Cholesterol / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D012968:Etidronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D008081:Liposomes; D008168:Lung / Q000378:metabolism*; D008297:Male; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry; D051381:Rats; D000068296:Risedronic Acid; D014018:Tissue Distribution
D000336:Aerosols; D000588:Amines; D050071:Bone Density Conservation Agents; D004337:Drug Carriers; D008081:Liposomes; D010743:Phospholipids; D002784:Cholesterol; C009317:stearylamine; D000068296:Risedronic Acid; D012968:Etidronic Acid