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Design of Biodegradable Hydrogel for the Local and Sustained Delivery of Angiogenic Plasmid DNA

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Abstract

Purpose

To attain the effective local and sustained delivery of plasmid DNA (pDNA) encoding for a growth factor.

Methods

We hypothesized that controlling the degradation rate of biomaterials encapsulating pDNA via concurrent physical dissociation of the cross-linked structure and hydrolytic chain breakage of polymers would allow one to significantly broaden the range of pDNA release rate. This hypothesis was examined using ionically cross-linked polysaccharide hydrogels which were previously designed to rapidly degrade via engineering of ionic cross-linking junction and partial oxidation of polysaccharide chains.

Results

The hydrogel degradation rates were varied over the broad range, and pDNA release correlated with the gel degradation rate. Degradable hydrogels were used for the local and sustained delivery of a pDNA encoding for vascular endothelial growth factor (VEGF) in the ischemic hindlimbs of mice, and local pDNA release significantly improved the recovery of blood perfusion as compared with a bolus injection of VEGFencoding pDNA.

Conclusion

This strategy to control the hydrogel degradation rate may be useful in regulating the delivery of a broad array of macromolecular drugs, and subsequently improve their therapeutic efficacy.

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Acknowledgement

The authors thank the NIH (RO1 DE013033 and RO1 HL069957) for the financial support of this research. The authors also thank Mr. Francis Rauh of FMC Corporation for supplying the alginate samples.

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Authors and Affiliations

  1. Division of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, 02138, USA

    Hyun Joon Kong, Eun Seok Kim & David J. Mooney

  2. Department of Chemical and Biomolecular Engineering, Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, 48109, USA

    Hyun Joon Kong

  3. School of Medicine, Chungnam National University, Daejeon, South Korea

    Eun Seok Kim

  4. Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, 48109, USA

    Yen-Chen Huang

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  1. Hyun Joon Kong
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Correspondence to David J. Mooney.

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Kong, H.J., Kim, E.S., Huang, YC. et al. Design of Biodegradable Hydrogel for the Local and Sustained Delivery of Angiogenic Plasmid DNA. Pharm Res 25, 1230–1238 (2008). https://doi.org/10.1007/s11095-007-9526-7

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  • DOI: https://doi.org/10.1007/s11095-007-9526-7

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