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Controlled Release of Plasmid DNA from a Genetically Engineered Silk-Elastinlike Hydrogel
Authors:Megeed  Zaki  Cappello  Joseph  Ghandehari  Hamidreza
Affiliation:(1) Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 North Pine Street, Baltimore, Maryland, 21201;(2) Protein Polymer Technologies, Inc., 10655 Sorrento Valley Road, San Diego, California, 92121
Abstract:Purpose. The purpose of this study was to evaluate the potential of a genetically engineered silk-elastinlike polymer (SELP) as a matrix for the controlled release of plasmid DNA.Methods. The influences of SELP concentration, DNA concentration, SELP cure time, and buffer ionic strength on the release of DNA from SELP hydrogels were investigated. To calculate the average effective diffusivity of DNA within the hydrogels, the release data were fitted to a known equation.Results. DNA was released from SELP hydrogels by an ion-exchange mechanism. Under the conditions studied, the release rate was influenced by buffer ionic strength, SELP concentration, and SELP cure time but not DNA concentration. The apparent diffusivity of pRL-CMV plasmid DNA in SELP hydrogels ranged from 3.78 ± 0.37 × 10-10 cm2/s (for hydrogels containing 12% w/w SELP and cured for 4 h) to 4.69 ± 2.81 × 10-9 cm2/s (for hydrogels containing 8% w/w SELP and cured for 1 h).Conclusions. The ability to precisely customize the structure and physicochemical properties of SELPs using recombinant techniques, coupled with their ability to form injectable, in situ hydrogel depots that release DNA, renders this class of polymers an interesting candidate for further evaluation in controlled gene delivery.
Keywords:genetically engineered polymers  controlled release  gene delivery  silk-elastinlike polymers  hydrogels
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