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

Eur J Pharm Sci. 2001 Aug;14(1):37-46. doi: 10.1016/s0928-0987(01)00147-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1,2-Dipalmitoylphosphatidylcholine
  • Adhesiveness
  • Cells, Cultured
  • Chemical Phenomena
  • Chemistry, Physical
  • Cholesterol / chemistry
  • Drug Carriers
  • Drug Delivery Systems*
  • Drug Stability
  • Humans
  • Lectins*
  • Liposomes
  • Lung / metabolism*
  • Nebulizers and Vaporizers
  • Pulmonary Alveoli / cytology
  • Pulmonary Alveoli / drug effects
  • Pulmonary Surfactants / pharmacology

Substances

  • Drug Carriers
  • Lectins
  • Liposomes
  • Pulmonary Surfactants
  • 1,2-Dipalmitoylphosphatidylcholine
  • Cholesterol