Document Detail

Influence of injection site, microvascular pressure and ultrasound variables on microbubble-mediated delivery of microspheres to muscle.
MedLine Citation:
PMID:  11849875     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: Our objective was to test the hypothesis that the ultrasound pulsing interval (PI), microbubble injection site and microvascular pressure significantly influence the transport of 100-nm microspheres to muscle through extravasation sites created by the destruction of microbubbles with ultrasound. BACKGROUND: Microbubbles show promise as targeted drug and gene delivery agents; however, designing optimal microbubble-based therapies will require an understanding of the factors that influence the transport of microbubble-delivered, gene-bearing vehicles to tissue. METHODS: Ultrasound at 1 MHz, with a peak negative pressure amplitude of 0.75 MPa, was applied to microbubbles and 100-nm microspheres in exteriorized rat spinotrapezius muscle. Ultrasound PIs of 1, 3, 5 and 10 s, arterial microsphere injection times of 10 or 40 s and arterial versus venous injection sites were tested. RESULTS: Extravasation point creation and microsphere delivery were greatest when the ultrasound PI was 5 or 10 s. No significant differences in extravasation point creation or microsphere delivery were observed with arterial versus venous microbubble injection, but a trend toward increased microsphere delivery with arterial injection may exist. Decreasing the arterial injection time from 40 to 10 s increased microvascular pressure, which, in turn, substantially enhanced microsphere transport to tissue, without a concomitant increase in the number of extravasation points. CONCLUSIONS: The ultrasound PI and microvascular pressure significantly influence the creation of extravasation points and the transport of microspheres to tissue. These factors may be important in designing and optimizing contrast ultrasound-based therapies.
Ji Song; John C Chappell; Ming Qi; Eric J VanGieson; Sanjiv Kaul; Richard J Price
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  39     ISSN:  0735-1097     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-02-18     Completed Date:  2002-03-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  726-31     Citation Subset:  AIM; IM    
Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA.
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MeSH Terms
Blood Pressure / physiology*
Capillary Permeability / physiology*
Cardiomyopathies / physiopathology,  therapy*,  ultrasonography*
Disease Models, Animal
Drug Carriers / administration & dosage*
Drug Delivery Systems*
Extravasation of Diagnostic and Therapeutic Materials / physiopathology
Injections, Intra-Arterial
Injections, Intramuscular
Muscle, Skeletal / physiopathology*,  ultrasonography*
Rats, Sprague-Dawley
Ultrasonography, Doppler, Pulsed*
Grant Support
Reg. No./Substance:
0/Drug Carriers

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