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.
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.
Authors: F Kurtis Kasper; Stephanie K Seidlits; Andrew Tang; Roger S Crowther; Darrell H Carney; Michael A Barry; Antonios G Mikos Journal: J Control Release Date: 2005-04-26 Impact factor: 9.776
Authors: Catarina Madeira; Luís M S Loura; M Raquel Aires-Barros; Aleksander Fedorov; Manuel Prieto Journal: Biophys J Date: 2003-11 Impact factor: 4.033
Authors: Jessica A DeQuach; Joy E Lin; Cynthia Cam; Diane Hu; Michael A Salvatore; Farah Sheikh; Karen L Christman Journal: Eur Cell Mater Date: 2012-06-05 Impact factor: 3.942
Authors: Justin L Madrigal; Shonit N Sharma; Kevin T Campbell; Roberta S Stilhano; Rik Gijsbers; Eduardo A Silva Journal: Acta Biomater Date: 2018-02-02 Impact factor: 8.947