Intramuscular delivery of DNA releasing microspheres

Microsphere properties and transgene expression

Jae-Hyung Jang, Lonnie D. Shea

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Plasmid-loaded microspheres can provide localized and sustained release into the target tissue, and thus have the potential to enhance the efficiency of naked DNA at promoting transgene expression. In this report, microsphere design parameters are investigated by correlating the extent and duration of transgene expression intramuscularly to the polymer molecular weight and the mass of DNA delivered. Plasmid DNA was incorporated into poly (lactide-co-glycolide) microspheres using a cryogenic double emulsion process, and microspheres were injected intramuscularly. Bolus injection of naked plasmid was used for control, which exhibited transfection of muscle cells with transgene expression that gradually decreased over time. Microspheres fabricated from low molecular weight polymer had expression levels that increased from day 1 to day 92, which subsequently decreased through day 174. Decreasing the microsphere mass delivered resulted in steady expression during the same time. However, microspheres fabricated with high molecular weight polymer had expression for only 14 days. Intramuscular injection resulted in a foreign body response to the microspheres, and these infiltrating cells adjacent were primarily transfected. This understanding of microsphere properties that determine transgene expression and the distribution of transfected cells may facilitate their application to fields such as tissue engineering or DNA vaccines.

Original languageEnglish
Pages (from-to)120-128
Number of pages9
JournalJournal of Controlled Release
Volume112
Issue number1
DOIs
Publication statusPublished - 2006 May 1

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Transgenes
Microspheres
DNA
Polymers
Plasmids
Molecular Weight
Polyglactin 910
DNA Vaccines
Intramuscular Injections
Tissue Engineering
Foreign Bodies
Emulsions
Muscle Cells
Transfection
Injections

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

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Intramuscular delivery of DNA releasing microspheres : Microsphere properties and transgene expression. / Jang, Jae-Hyung; Shea, Lonnie D.

In: Journal of Controlled Release, Vol. 112, No. 1, 01.05.2006, p. 120-128.

Research output: Contribution to journalArticle

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