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

Robert L. Cleek; Ajay A. Rege; Larry A. Denner; Suzanne G. Eskin; Antonios G. Mikos

doi:10.1002/(SICI)1097-4636(19970615)35:4<525::AID-JBM12>3.0.CO;2-A

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

Robert L. Cleek, Ajay A. Rege, Larry A. Denner, Suzanne G. Eskin, Antonios G. Mikos

Research output: Contribution to journal › Article › peer-review

78 Scopus citations

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.

Original language	English (US)
Pages (from-to)	525-530
Number of pages	6
Journal	Journal of Biomedical Materials Research
Volume	35
Issue number	4
DOIs	https://doi.org/10.1002/(SICI)1097-4636(19970615)35:4<525::AID-JBM12>3.0.CO;2-A
State	Published - Jun 15 1997
Externally published	Yes

ASJC Scopus subject areas

Biomaterials
Biomedical Engineering

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10.1002/(SICI)1097-4636(19970615)35:4<525::AID-JBM12>3.0.CO;2-A

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title = "Inhibition of smooth muscle cell growth in vitro by an antisense oligodeoxynucleotide released from poly(DL-lactic-co-glycolic acid) microparticles",

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.",

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AU - Cleek, Robert L.

AU - Rege, Ajay A.

AU - Denner, Larry A.

AU - Eskin, Suzanne G.

AU - Mikos, Antonios G.

PY - 1997/6/15

Y1 - 1997/6/15

N2 - 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.

AB - 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.

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

Abstract

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