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Enhanced Protein Delivery from Photopolymerized Hydrogels Using a Pseudospecific Metal Chelating Ligand

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Purpose

This study was conducted to investigate the cause of incomplete protein release from photopolymerized poly(ethylene glycol) (PEG) hydrogels and verify the protein-protection mechanism provided by iminodiacetic acid (IDA).

Methods

The in vitro release of bovine serum albumin (BSA) from PEG hydrogels prepared under different conditions was studied. Photoinitiator and initial protein concentrations were varied as well as the addition of IDA and metal ions. Protein immobilization within the nondegradable networks via free-radical reaction was demonstrated by gel electrophoresis.

Results

Protein release efficiency was shown to be dependent on photoinitiator and initial protein concentration. Gel electrophoresis results revealed immobilization of protein to the polymer network and further indicated the detrimental role of free radicals in lowering protein-release efficiency. Adding IDA to the prepolymer solution enhanced total protein release from the subsequently photopolymerized network in a dose-dependent manner. The addition of metal ions including Cu2+, Zn2+, and Ni2+ further increased BSA release efficiency. Agreement between the protein release data and theoretical model predictions accounting for reversible protein–IDA binding further validated the protection effect provided by IDA and IDA-transition metal complexes.

Conclusions

The protection effect described in this study offers a novel strategy for increasing the delivery efficiencies of many therapeutically valuable proteins.

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Acknowledgments

The authors wish to acknowledge Drs. Sarah Harcum, James Morris, and Meredith Morris for discussion in SDS-PAGE. The project was supported in part by funding from NSF-EPSCoR.

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Authors and Affiliations

  1. Department of Bioengineering, Clemson University, Clemson, South Carolina, 29634, USA

    Chien-Chi Lin & Andrew T. Metters

  2. Department of Chemical and Biomolecular Engineering, Clemson University, 127 Earle Hall, Clemson, South Carolina, 29634, USA

    Andrew T. Metters

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  1. Chien-Chi Lin
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Correspondence to Andrew T. Metters.

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Lin, CC., Metters, A.T. Enhanced Protein Delivery from Photopolymerized Hydrogels Using a Pseudospecific Metal Chelating Ligand. Pharm Res 23, 614–622 (2006). https://doi.org/10.1007/s11095-005-9395-x

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