Pharmaceutical evaluation of gas-filled microparticles as gene delivery system

To produce and characterize a nonviral ultrasound-controlled release system of plasmid DNA (pDNA) encapsulated in gas-filled poly(D,L-lactide-co-glycolide) microparticles (PLGA-MPs). Different cationic polymers were used to form pDNA/polymer complexes to enhance the stability of pDNA during micropar...

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Bibliographic Details
Published in:Pharmaceutical research 2002-03, Vol.19 (3), p.250-257
Main Authors: SEEMANN, Stefanie, HAUFF, Peter, SCHULTZE-MOSGAU, Marcus, LEHMANN, Cathleen, RESZKA, Regina
Format: Article
Language:English
Subjects:
Acoustics
Adenoviruses
Biological and medical sciences
Contrast agents
Drug Delivery Systems - methods
Drug Evaluation, Preclinical - methods
Efficiency
Gases - administration & dosage
Gene therapy
General pharmacology
Genetic Therapy - methods
Humans
Lactic Acid - administration & dosage
Lipids
Medical sciences
Microspheres
Particle Size
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Plasmids - administration & dosage
Polyglycolic Acid - administration & dosage
Polylactic Acid-Polyglycolic Acid Copolymer
Polymers
Polymers - administration & dosage
Ultrasonic imaging
Vectors (Biology)
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Summary:To produce and characterize a nonviral ultrasound-controlled release system of plasmid DNA (pDNA) encapsulated in gas-filled poly(D,L-lactide-co-glycolide) microparticles (PLGA-MPs). Different cationic polymers were used to form pDNA/polymer complexes to enhance the stability of pDNA during microparticle preparation. The physico-acoustical properties of the microparticles, particle size, pDNA integrity, encapsulation efficiency and pDNA release behavior were studied in vitro. The microparticles had an average particle size of around 5 microm. More than 50% of all microparticles contained a gas core, and when exposed to pulsed ultrasound as used for color Doppler imaging create a signal that yields typical color patterns (stimulated acoustic emission) as a result of the ultrasound-induced destruction of the microparticles. Thirty percent of the pDNA used was successfully encapsulated and approximately 10% of the encapsulated pDNA was released by ultrasound within 10 min. Plasmid DNA can be encapsulated in biodegradable gas-filled PLGA-MPs without hints for a structural disintegration. A pDNA release by ultrasound-induced microparticle-destruction could be shown in vitro.
ISSN:0724-8741
1573-904X
DOI:10.1023/a:1014430631844