title: Liposomes prolong the therapeutic effect of anti-asthmatic medication via pulmonary delivery.
abstract: OBJECTIVE
  The main objective of this study was to develop a novel aerosolized liposome formulation for pulmonary delivery of anti-asthmatic medication and to explore the relationship between the bioavailability and anti-asthmatic efficacy of such a formulation. Asthma treatment usually requires frequent administration of medication for sustained bronchodilating response. Liposomes are known for their capability for sustained drug release and thus would be a suitable delivery system for anti-asthmatic medication for prolonged therapeutic effect. Salbutamol sulfate (SBS) was chosen as the model drug in this study because of its high water solubility and fast absorption after administration.
  
  
  METHODS
  SBS was efficiently encapsulated into liposomes by the vesicular phospholipid gel technique. SBS permeability across the pulmonary membrane of an Asian toad was determined by in vitro study. Intratracheal administration of liposomes labeled with the fluorescent dye 1,1'-dioctadecyltetramethyl indotricarbocyanine iodide (DiR) in a rat model was assessed by a small animal imaging system and pharmacokinetic analysis. Pharmacodynamic analysis was performed in guinea pigs using the Konzett-Rössler method.
  
  
  RESULTS
  SBS was efficiently encapsulated into liposomes with encapsulation efficiency as high as 70%. The particle size of the SBS liposome suspension was approximately 57 ± 21 nm. In the in vitro study of permeability across the pulmonary membrane of Asian toads, SBS from liposomes demonstrated a slower transport rate compared to free SBS solution. Pulmonary delivery of liposomes in a rat model showed that the liposomes were effectively distributed in the respiratory tract and lungs, and that the release of SBS from liposomes was sustained for at least 48 hours. Pharmacodynamic analysis in a guinea pig model showed that the anti-asthmatic effect of SBS liposomes persisted for up to 18 hours, whereas that of free SBS solution was less than 8 hours.
  
  
  CONCLUSIONS
  The overall results demonstrated that liposomes could increase the concentration and retention time of SBS in the lungs and therefore prolong its therapeutic effect.
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Chen
authors.forename: Wenhua
authors.initials: W
authors.lastname: Huang
authors.forename: Blenda Chi
authors.initials: BC
authors.lastname: Wong
authors.forename: Linlin
authors.initials: L
authors.lastname: Yin
authors.forename: Yuen Fan
authors.initials: YF
authors.lastname: Wong
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000280:Administration, Inhalation; D000420:Albuterol / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001001:Anura; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005456:Fluorescent Dyes; D006168:Guinea Pigs; D006632:Histamine / Q000009:adverse effects; D016014:Linear Models; D008081:Liposomes / Q000494:pharmacology*; D008168:Lung / Q000737:chemistry / Q000378:metabolism; D008297:Male; D010316:Particle Size; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018927:Anti-Asthmatic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005456:Fluorescent Dyes; D008081:Liposomes; D006632:Histamine; D000420:Albuterol