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Liposomes prolong the therapeutic effect of anti-asthmatic medication via pulmonary delivery

Authors Chen X, Huang W, Wong BC, Yin L, Wong YF, Xu M, Yang Z

Received 7 November 2011

Accepted for publication 15 December 2011

Published 28 February 2012 Volume 2012:7 Pages 1139—1148

DOI https://doi.org/10.2147/IJN.S28011

Review by Single-blind

Peer reviewer comments 2

Xiaoyu Chen, Wenhua Huang, Blenda Chi Kwan Wong, Linlin Yin, Yuen Fan Wong, Min Xu, Zhijun Yang

School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong

Purpose: 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.
Conclusion: The overall results demonstrated that liposomes could increase the concentration and retention time of SBS in the lungs and therefore prolong its therapeutic effect.

Keywords: salbutamol sulfate, asthma, intratracheal administration, sustained release

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