Inhibition of smooth muscle cell growth in vitro by an antisense oligodeoxynucleotide released from poly(DL-lactic-co-glycolic acid) microparticles.
We fabricated poly(DL-lactic-co-glycolic acid) (PLGA) 50:50 microparticles loaded with an antisense (AS) oligodeoxy-nucleotide (ODN) against the rat tenascin mRNA and determined the effect in vitro of the AS-ODN released on smooth muscle cell (SMC) proliferation and migration. AS-ODN was entrapped using a double-emulsion-solvent-extraction technique with high efficiency. Release of AS-ODN was characterized by a small initial-burst effect followed by a period of controlled AS-ODN release for up to 20 days. SMC proliferation studies exhibited dose-dependent growth inhibition with AS-ODN-loaded microparticles. Microparticles loaded with scrambled (SC) ODN showed less growth inhibition than AS-ODN. Moreover, only the AS-ODN-loaded microparticles inhibited migration. These results demonstrate the feasibility of entrapping an AS-ODN to rat tenascin in PLGA microparticles for controlled delivery to inhibit SMC proliferation and migration.
Cleek
R L
RL
Cox Laboratory for Biomedical Engineering, Department of Chemical Engineering, Rice University, Houston, Texas 77251-1892, USA.
Rege
A A
AA
Denner
L A
LA
Eskin
S G
SG
Mikos
A G
AG
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D004337:Drug Carriers; D008863:Microspheres; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011108:Polymers; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D019063:Tenascin / Q000235:genetics
D004337:Drug Carriers; D016376:Oligonucleotides, Antisense; D011108:Polymers; D012333:RNA, Messenger; D019063:Tenascin; C048851:polysorb