title: Wet sol-gel derived silica for controlled release of proteins.
abstract: 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 SiO(2) 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.
authors.affiliation: University of Padova, Department of Pharmaceutical Sciences, Via Marzolo 5, 35131-Padova, Italy.
authors.forename: Deborah
authors.initials: D
authors.lastname: Teoli
authors.forename: Laura
authors.initials: L
authors.lastname: Parisi
authors.forename: Nicola
authors.initials: N
authors.lastname: Realdon
authors.forename: Massimo
authors.initials: M
authors.lastname: Guglielmi
authors.forename: Antonio
authors.initials: A
authors.lastname: Rosato
authors.forename: Margherita
authors.initials: M
authors.lastname: Morpurgo
mesh_terms: D000818:Animals; D002942:Circular Dichroism; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D004339:Drug Compounding; D004355:Drug Stability; D005260:Female; D007526:Isoelectric Point; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D044367:Phase Transition; D011506:Proteins / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D058428:Silica Gel; D012822:Silicon Dioxide / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012995:Solubility; D013997:Time Factors; D017155:Wettability
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011506:Proteins; D058428:Silica Gel; D012822:Silicon Dioxide