Pharmaceutical evaluation of gas-filled microparticles as gene delivery system.
OBJECTIVE
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 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.


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.
Seemann
Stefanie
S
Schering AG, Research Laboratories, Berlin, Germany.
Hauff
Peter
P
Schultze-Mosgau
Marcus
M
Lehmann
Cathleen
C
Reszka
Regina
R
D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005740:Gases / Q000008:administration & dosage*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage*; D008863:Microspheres; D010316:Particle Size; D010957:Plasmids / Q000008:administration & dosage*; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage*
D005740:Gases; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid