Inhibition of smooth muscle cell growthin vitro by an antisense oligodeoxynucleotide released from poly(DL-lactic-co-glycolic acid) microparticles

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Abstract
We fabricated poly(DL‐lactic‐co‐glycolic acid) (PLGA) 50:50 microparticles loaded with an antisense (AS) oligodeoxynucleotide (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. © 1997 John Wiley & Sons, Inc.