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. 2009 Feb 23;368(1-2):215-9.
doi: 10.1016/j.ijpharm.2008.10.021. Epub 2008 Nov 5.

Influence of polymer structure and biodegradation on DNA release from silk-elastinlike protein polymer hydrogels

David Hwang  1 , Vikas Moolchandani, Ramesh Dandu, Mohamed Haider, Joseph Cappello, Hamidreza Ghandehari
Affiliations

Influence of polymer structure and biodegradation on DNA release from silk-elastinlike protein polymer hydrogels

David Hwang et al. Int J Pharm. .

Abstract

Silk-elastinlike protein polymers (SELPs) of varying ratios and lengths of silk and elastin blocks capable of hydrogel formation were evaluated as matrices for controlled delivery of plasmid DNA. Influence of polymer structure, ionic strength of the media and gelation time on DNA release from two structurally related hydrogels, SELP-47K and SELP-415K, was evaluated. The influence of elastase-induced degradation on the swelling behavior and DNA release from these hydrogels was investigated. Results indicate that release is a function of polymer structure, concentration and cure time. SELP-415K which has twice the number of elastin units as that of SELP-47K demonstrated higher release than that of SELP-47K. DNA release from these hydrogels is an inverse function of polymer concentration and cure time, with higher release observed at lower polymer concentration and shorter cure time. Results indicate that ionic strength of the media governs the rate of release. An increase in swelling ratio was observed in the presence of elastase at 12 wt.% composition for both SELP analogs. Release in the presence of elastase was enhanced due to increased swelling ratio and loss of hydrogel integrity. These studies allude to the utility of recombinant techniques to control plasmid DNA release and biodegradation in SELP hydrogels.

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Figures

Fig. 1
Fig. 1
Amino acid sequences of: A) SELP 47K; B) SELP 415K. Lys (K) residues underlined. The elastin blocks are highlighted in gray. Head and tail sequences not shown.
Fig. 2
Fig. 2
Influence of polymer structure and cure time (CT) on DNA release from 12 wt% SELP hydrogels at pH=7.4 and μ=0.16 M released over a 28 day period. Symbols represent SELP-415K at 4 hr cure time (CT) (◆) and 48 hr CT (■), and SELP-47K at 4 hr CT (▲) and 48 hr CT (X) respectively. Each symbol represents mean ± standard deviation for n=3 samples.
Fig. 3
Fig. 3
Influence of ionic strength on DNA release from SELP 415K hydrogels at pH=7.4. Symbols represent release at 0.016M (◆), 0.16M (■) and 1.6M (▲). Each symbol represents mean ± standard deviation for n=3 samples.
Fig. 4
Fig. 4
Influence of polymer structure and ionic strength on the turbidity of DNA (at room temperature): Symbols represent absorbance of polymer complexes of SELP-415K at 0.016M (◆) and 0.16M (▲), and SELP-47K at 0.016M (■) and 0.16M (formula image). Each symbol represents mean ± standard deviation for n=3 samples.
Fig. 5
Fig. 5
Influence of elastase on the swelling behavior of SELP hydrogels as a function of polymer concentration and structure. The bars represent q of SELP hydrogels (i) in the presence (white) and absence (black) of elastase. Each bar represents mean ± standard deviation for n=3 samples.
Fig. 6
Fig. 6
Influence of elastase-induced degradation on release of DNA from SELP hydrogel analogs. Symbols represent cumulative percent release of DNA from 12wt% hydrogels of SELP-47K in the presence (△) and absence (▲) of elastase, and SELP-415K in the presence (◇) and absence (◆) of elastase. Each symbol represents mean ± standard deviation for n=3 samples.
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