Journal
JOURNAL OF CONTROLLED RELEASE
Volume 116, Issue 3, Pages 295-303Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2006.09.010
Keywords
sol-gel; silica; controlled release; protein drugs; parenteral administration
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The potential of wet sol-gel derived silica gels as new matrices for the entrapment and sustained release of proteins was investigated. Model proteins, BSA, ribonuclease-A and avidin, with differing molecular weights and/or isoelectric points, were entrapped in two silica polymer formulations having different silica. contents (4% and 12% wt/v). The conformational stability of the proteins after entrapment and their release after immersion into physiological conditions were measured. Circular dichroism analysis showed that protein conformation is maintained after entrapment and stability is enhanced. Protein-free formulations were injected intramuscularly into BALB/c mice to monitor the in vivo fate of the matrix, and the results showed that the gel is totally reabsorbed, without any apparent surrounding inflammation process. The time required for matrix bioerosion varied between one to three weeks, depending on its SiO2 content. Erosion was also measured in vitro and the contribution of erosion and diffusion to the release of the embedded proteins was quantified. These data indicate that wet silica polymers obtained by the sol-gel route are promising matrices for the sustained release of protein drugs. (c) 2006 Elsevier B.V. All rights reserved.
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