Classifications

• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
  • C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
  • C08G77/02—Polysilicates

Definitions

• the protein is inserted into a high molecular weight assembly obtained with either a polymer (implants, nano or microparticles) or by self assembly of low molecular lipid entities (liposomes).
• US published Application 2003/0148291 describes the immobilization into sol-gel derived silica polymers of all class of generic bioactive macromolecules whose bioactivity is to be exerted into the immobilized silica system characterized by the fact that the entrapped molecules must not leach out of the gel.
• US Patents 6303290 and 6495352 Bl describe the immobilization of biomolecules into silica gels prepared from silicon dioxide and alkaline solutions differing from the classic alkoxysilane sol-gel route. Besides, the applications are restricted to those that require physical entrapment of biomolecules.
• Sol-gel silica polymers described in the literature are most commonly used in their dry form, which is obtained after removal, by evaporation or sublimation, of water and organic solvents deriving from the polymerization process. Solvent removal by evaporation causes irreversible syneresis of the silica polymer, increasing the interconnections of the silica network.
• FITC modified r-hGH was obtained as described in example 2 and FITC-r-hGH loaded wet gels (cylinders, lOO ⁇ l, 4%, 12% and 20% SiO 2 ) were prepared as described in example 1 and immersed, at 37°C into 50 ml of sterile PBS buffer, constantly agitated. Aliquots of supernatant were removed at scheduled times for protein content determination and replaced with fresh buffer. The amount of buffer used was such that it allowed total dissolution of all of the SiO 2 in the gel (sink conditions for silica.). Protein concentration in the release samples was measured either by fluorescence and/or RP-HPLC (Phenomenex C- 18 column). The results ( Figure 9) show quantitative recovery of the embedded protein and demonstrate that release kinetics may be modulated by varying the wet gel SiO 2 content.
• EXAMPLE 8 In vitro sustained release of recombinant human Growth Hormon (r-hGH) from gels composed of pure silica or containing also alkyl- modified silanes
• Protein concentration in the release samples was measured either by fluorescence and/or RP-HPLC (Phenomenex C- 18 column).
• Figure 10 shows that the release kinetic depends both on gel loading and polymer composition.
• Formulations containing the T-C 16 residue display higher r-hGH retenting properties as compared to purely inorganic ones.
• EXAMPLE 9 In vitro release of r-hGH from microspheres containing different amounts of alkyl siloxane residue.
• Gel were loaded at 3 mg r-hGH/g wet gel and were immersed and constantly agitated at 37°C into sterile PBS buffer, in sink conditions for silica dissolution. Aliquots of supernatant were removed at scheduled times for protein content determination and replaced with fresh buffer.
• EXAMPLE 10 In vivo fate of wet gel formulation upon s.c. parenteral administration.
• the 4% gel appeared heavily infiltrated by very few granulocytes and high numbers of mononuclear cells resembling small lymphocytes. Macrophages were almost not present, nor were signs of inflammatory events in the subcutaneous tissues immediately surrounding the gel deposit, at any time point tested. Conversely, the 12% gel induced an initial cell infiltrate mainly represented by granulocytes which were subsequently replaced by an heavy macrophage component and few lymphocytes.
• Liu DM and Chen I-W (2001) Encapsulation of biomaterials in porous glasslike matrices prepared via an aqueous colloidal sol-gel process, The Trustees of the

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• Chemical & Material Sciences (AREA)
• Health & Medical Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Medicinal Chemistry (AREA)
• Polymers & Plastics (AREA)
• Organic Chemistry (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
• Medicinal Preparation (AREA)

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• 2006
  • 2006-04-12 IT ITMI20060734 patent/ITMI20060734A1/it unknown
• 2007
  • 2007-02-23 EP EP07712309A patent/EP2004727A1/en not_active Withdrawn
  • 2007-02-23 WO PCT/EP2007/051762 patent/WO2007115860A1/en active Application Filing
  • 2007-02-23 JP JP2009504660A patent/JP2009533373A/ja active Pending

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