Pharmaceutical Evaluation of Gas-Filled Microparticles as Gene Delivery System |
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Authors: | Seemann Stefanie Hauff Peter Schultze-Mosgau Marcus Lehmann Cathleen Reszka Regina |
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Institution: | (1) Schering AG, Research Laboratories, 13342 Berlin, Germany;(2) Max-Delbrueck-Center for Molecular Medicine, AG Drug Targeting, Robert-Roessle-Strasse 10, 13092 Berlin, Germany |
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Abstract: | Purpose. 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).
Methods. 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.
Results. The microparticles had an average particle size of around 5 m. 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.
Conclusions. 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. |
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Keywords: | controlled release DNA gene therapy microparticles poly(D L-lactide-co-glycolide) ultrasound |
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