title: Lectin-functionalized liposomes for pulmonary drug delivery: effect of nebulization on stability and bioadhesion.
abstract: The generation of respirable aerosols of a functionalized colloidal carrier has been investigated in this study. Lectin-functionalized liposomes, which proved to show improved cell association (using A549 cell line and primary human alveolar cells) even in the presence of a commercial lung surfactant preparation, have been developed. The stability of non-functionalized liposomes during nebulization using a jet nebulizer (Pari II provocation nebulizer, operated using an air flow of 30 l/min) was firstly investigated, and the experimental and formulation conditions were optimized and applied for the preparation of lectin-functionalized liposomes. The incorporation of cholesterol enhanced the stability of the liposomes during nebulization (from 15-20% leakage of a hydrophilic marker to 8% upon cholesterol incorporation) and upon incubation with lung surfactant preparation. Nebulization of the functionalized liposomes did not significantly influence their physical stability. Their enhanced cell binding capability (compared to non-functionalized liposomes) was also maintained. A drop in cell association compared to fresh functionalized liposomes was detected after nebulization, nevertheless, the binding was still significantly higher than that of the non-functionalized liposomes. The deposition of the liposomal preparation in lung periphery, proved by the deposition of the liposomal preparation on the lower stages of an ASTRA type cascade impinger and a mean median aerodynamic diameter (MMAD) of 2.85 microm, makes it a potential candidate as a macromolecule-drug carrier for local and/or systemic administration.
authors.affiliation: Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, P.O. Box 15 11 50, D-66041, Saarbrücken, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Abu-Dahab
authors.forename: U F
authors.initials: UF
authors.lastname: Schäfer
authors.forename: C M
authors.initials: CM
authors.lastname: Lehr
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine; D000268:Adhesiveness; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002784:Cholesterol / Q000737:chemistry; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004355:Drug Stability; D006801:Humans; D037102:Lectins; D008081:Liposomes; D008168:Lung / Q000378:metabolism*; D009330:Nebulizers and Vaporizers; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects; D011663:Pulmonary Surfactants / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D037102:Lectins; D008081:Liposomes; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine; D002784:Cholesterol