NDLI: Inhibition of Tracheal Vascular Extravasation by Liposome-Encapsulated Albuterol in Rats

Content Provider	Springer Nature Link
Author	Zhang, Weiming Guo, Luke Nadel, Jay A. Papahadjopoulos, Demetrios
Copyright Year	1998
Abstract	Purpose. To develop a liposome-based system for systemic delivery of anti-inflammatory drugs to airways and other inflamed tissues. Methods. Postcapillary venular gap junctions open during airway inflammation and allow fluid accumulation and permit molecules (e.g. complement, kininogen) to enter tissues, initiating inflammatory cascades. Beta-adrenergic agonists prevent inflammatory plasma extravasation, but because of their deleterious side effects, they are not used intravenously. When sterically stabilized "stealth” liposomes are injected iv, they remain in the circulation for long periods. Inflammatory mediators [e.g., substance P(SP)] open postcapillary venular gaps and allow liposomes and their contents to be deposited selectively in the inflamed tissue. Results. We hypothesized that liposomes encapsulating a beta-adrenergic agonist, such as albuterol, would deposit selectively in inflamed airway tissue, where the drug would slowly leak out of the liposomes, resulting in closure of the gaps, thus preventing subsequent inflammatory extravasation. To test this hypothesis, we delivered albuterol-loaded liposomes iv in rats. Then we injected SP to open the venular gaps and allow accumulation of the drug-loaded liposomes in airway tissue. We examined whether this treatment resulted in inhibition of subsequent plasma extravasation induced by SP. The results indicate that liposome-encapsulated albuterol inhibits subsequent extravasation, presumably by leaking out of liposomes in airway tissue. This inhibition occurs for prolonged periods of time and with limited side effects compared to the effect of free albuterol. Conclusions. We conclude that liposomes loaded with appropriate drugs, by migrating to inflamed tissue and subsequently inhibiting inflammatory cascades, may be of therapeutic value in inflammatory diseases.
Starting Page	455
Ending Page	460
Page Count	6
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	15
Issue Number	3
e-ISSN	1573904X
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	1998-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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