title: Liposomes for drug delivery to the lungs by nebulization.
abstract: Preparation of drug-loaded freeze-dried (FD) liposomes, designed for delivery to lungs after rehydration/nebulization was investigated. Rifampicin (RIF) incorporating multilamelar (MLV) and dried rehydrated vesicles (DRV); composed of phosphatidylcholine (PC), dipalmitoyloglycero-PC (DPPC) or distearoyloglycero-PC (DSPC), containing or not Cholesterol (Chol), were prepared. Vesicles were characterized for encapsulation efficiency (EE%), size distribution, zeta-potential, stability during freeze drying (FD) and nebulization (nebulization efficiency (NE%) and retention of RIF after nebulization (NER%)). Mucoadhesion and toxicity in A549 cells was measured. RIF EE% was not affected by liposome type but lipid composition was important; Synthetic lipid vesicles (DPPC and DSPC) had higher EE% compared to PC. As Chol increased EE% decreased. Freeze drying (FD) had no effect on EE%, however trehalose decreased EE% possibly due to RIF displacement. NER% was highly affected by lipid composition. Results of NE% and NER% for RIF-loaded liposomes show that DSPC/Chol (2:1) is the best composition for RIF delivery in vesicular form to lungs, by nebulization. Mucoadhesion and A549 cell toxicity studies were in line with this conclusion, however if mucoadhesion is required, improvement may be needed.
authors.affiliation: Department of Pharmacy, University of Patras, Rio, Greece.
authors.forename: Marco
authors.initials: M
authors.lastname: Zaru
authors.forename: Spyridon
authors.initials: S
authors.lastname: Mourtas
authors.forename: Pavlos
authors.initials: P
authors.lastname: Klepetsanis
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Fadda
authors.forename: Sophia G
authors.initials: SG
authors.lastname: Antimisiaris
mesh_terms: D000269:Adhesives; D000327:Adsorption; D000336:Aerosols; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000493:pharmacokinetics; D002152:Calorimetry, Differential Scanning; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D002784:Cholesterol / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005079:Excipients; D005612:Freeze Drying; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D008168:Lung / Q000378:metabolism*; D009092:Mucous Membrane; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011650:Pulmonary Alveoli / Q000378:metabolism; D012293:Rifampin / Q000008:administration & dosage / Q000493:pharmacokinetics; D013499:Surface Properties; D013778:Tetrazolium Salts; D013816:Thermodynamics; D013844:Thiazoles
chemical_list: D000269:Adhesives; D000336:Aerosols; D000904:Antibiotics, Antitubercular; D005079:Excipients; D008081:Liposomes; D013778:Tetrazolium Salts; D013844:Thiazoles; D002784:Cholesterol; C022616:thiazolyl blue; D012293:Rifampin