Polyvinyl Derivatives as Novel Interactive Polymers for Controlled Gene Delivery to Muscle View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1996-05

AUTHORS

Russell J. Mumper, John G. Duguid, Khursheed Anwer, Melisa K. Barron, Hiroaki Nitta, Alain P. Rolland

ABSTRACT

PURPOSE: DNA plasmids (pDNA) can be taken up by and expressed in striated muscle after direct intramuscular injection. We have developed interactive polymeric gene delivery systems that increase pDNA bioavailability to muscle cells by both protecting pDNA from nucleases and controlling the dispersion and retention of pDNA in muscle tissue. METHODS: A DNA plasmid, containing a CMV promoter and a galactosidase reporter gene (CMV-beta-gal), was injected either in saline or formulated in polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA) solutions. Interactions between PVP and pDNA were assessed by dynamic dialysis, Isothermal Titration Calorimetry (ITC), and Fourier Transformed Infra Red (FT-IR) spectroscopy. Formulations (50 mu l) were injected into rat tibialis muscles after surgical exposure. Immunohistochemistry for beta-gal was used to visualize the sites of expression in muscle. RESULTS: Beta-gal expression using pDNA in saline reached a plateau while beta-gal expression using PVP formulations increased linearly in the dose range studied (12.5-150 mu g pDNA injected) and resulted in an increase in the number and distribution of cells expressing beta-gal. The interaction between PVP and pDNA was found to be an endothermic process governed largely by hydrogen-bonding and results in protection of pDNA from extracellular nucleases. CONCLUSIONS: Significant enhancement of gene expression using interactive polyvinyl-based delivery systems has been observed. The improved tissue dispersion and cellular uptake of pDNA using polyvinyl-based systems after direct injection into muscle is possibly due to osmotic effects. More... »

PAGES

701-709

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1023/a:1016039330870

DOI

http://dx.doi.org/10.1023/a:1016039330870

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1006850729

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/8860424


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