Controlled release of plasmid DNA from a genetically engineered silk-elastinlike hydrogel.
OBJECTIVE
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 x 10(-10) cm2/s (for hydrogels containing 12% w/w SELP and cured for 4 h) to 4.69 +/- 2.81 x 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.
University of Maryland School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore 21201, USA.
Zaki
Z
Megeed
Joseph
J
Cappello
Hamidreza
H
Ghandehari
D000595:Amino Acid Sequence / Q000235:genetics; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000235:genetics*; D001704:Biopolymers; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods; D004549:Elastin / Q000008:administration & dosage / Q000235:genetics; D005349:Fibroins; D005353:Fibronectins; D005818:Genetic Engineering / Q000379:methods*; D020100:Hydrogels / Q000008:administration & dosage*; D008969:Molecular Sequence Data; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics; D011108:Polymers / Q000008:administration & dosage*; D011993:Recombinant Fusion Proteins; D047011:Silk
D001426:Bacterial Proteins; D001704:Biopolymers; D003692:Delayed-Action Preparations; D005353:Fibronectins; D020100:Hydrogels; D011108:Polymers; D011993:Recombinant Fusion Proteins; D047011:Silk; C089172:silk-like protein polymer; D004549:Elastin; D005349:Fibroins