Lectin-functionalized liposomes for pulmonary drug delivery: effect of nebulization on stability and bioadhesion

The generation of respirable aerosols of a functionalized colloidal carrier has been investigated in this study. Lectin-functionalized liposomes. whic h proved to show improved cell association (using A549 cell line and primar y human alveolar cells) even in the presence of a commercial lung surfactan t preparation. have been developed. The stability of non-functionalized lip osomes during nebulization using a jet nebulizer (Pari II provocation nebul izer, operated using an air flow of 30 1/min) was firstly investigated. and the experimental and formulation conditions were optimized and applied for the preparation of lectin-functionalized liposomes. The incorporation of c holesterol enhanced the stability of the liposomes during nebulization (fro m 15-20% leakage of a hydrophilic marker to 8% upon cholesterol incorporati on) and upon incubation with lung surfactant preparation. Nebulization of t he functionalized liposomes did not significantly influence their physical stability. Their enhanced cell binding capability (compared to non-function alized liposomes) was also maintained. A drop in cell association compared to fresh functionalized liposomes was detected after nebulization, neverthe less, the binding was still significantly higher than that of the non-funct ionalized liposomes. The deposition of the liposomal preparation in lung pe riphery, proved by the deposition of the liposomal preparation on the lower stages of an ASTRA type cascade impinger and a mean median aerodynamic dia meter (MMAD) of 2.85 mum, makes it a potential candidate as a macromolecule -drug carrier for local and/or systemic administration. (C) 2001 Elsevier S cience BY. All rights reserved.