Chitosan-coated liposomes for delivery to lungs by nebulisation.
The preparation of Chitosan (CHT)-coated liposomes and their applicability as a carrier for delivery of drugs to the lungs by nebulisation was investigated. Empty SUV (small unilamellar) liposomes were initially prepared (with different lipid compositions) and coated with CHT by dropwise addition of CHT solution in the liposome dispersion. CHT-coating efficiency was calculated after separation of coated/non-coated liposomes by centrifugation, and measurement of lipid in each fraction. After establishing the best conditions for CHT-coating (concentration of CHT in the solution), RIF-loaded CHT-coated liposomes, with different lipid compositions (negatively charged and non-charged) were constructed, and their encapsulation efficiency (EE) and nebulisation efficiency (NE%)/stability (NER%) were evaluated. Charged liposomes (containing phosphatidylglycerol [PG]) can be coated with CHT better compared to non-charged ones. The EE of CHT-coated liposomes (that contain PG) is slightly increased while their stability after nebulisation is significantly increased (NER%). Mucoadhesive properties of CHT-coated liposomes were substantially better (compared to non-coated ones) while the toxicity of liposomal RIF towards A549 epithelial cells was lower compared to free drug for all the types of vesicles evaluated, and especially the CHT-coated ones. Thereby, it is concluded that CHT-coated liposomes have advantages (compared to non-coated) when the delivery of drugs to the lungs by nebulisation is considered.
Zaru
Marco
M
Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, Rio 26510, Greece.
Manca
Maria-Letizia
ML
Fadda
Anna Maria
AM
Antimisiaris
Sophia G
SG
D000280:Administration, Inhalation; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry / Q000633:toxicity; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008081:Liposomes / Q000737:chemistry* / Q000633:toxicity*; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D012293:Rifampin / Q000008:administration & dosage*
D004337:Drug Carriers; D008081:Liposomes; D048271:Chitosan; D012293:Rifampin