Colloidal core-shell assemblies and methods of preparation
View Patent ↗This invention relates to a method of making a composition comprising a colloid comprising particles having a colloidal silica core and a shell, said method comprising the steps of: simultaneously introducing into a vessel a first liquid stream containing silica core particles, a second liquid stream containing a polymer having amine functionalities; and a third liquid stream having a pH adjusting substance such that said vessel is maintained at a pH below 6.0, and followed by readjusting the pH of the colloid to a pH between about 7-10; the addition of a cross-linking reagent, and adjusting the pH of the colloid to approximately physiological conditions, wherein the core-shell colloid contains between 10 and 30 μmol amine-monomer/m 2 core surface area.
1. A method of making a composition comprising a colloid which is stable under physiological pH and ionic strength, said colloid comprising particles having a colloidal silica core and a shell, said method comprising the steps of:
introducing into a vessel a first liquid stream containing core particles; simultaneously introducing into said vessel a second liquid stream containing a polymer made from a monomer having amine functionalities in an amount at least equal to the amount required to cover the surfaces of the core particles; and
simultaneously introducing into said vessel a third liquid stream having a pH adjusting substance at such a rate that the pH in said vessel is maintained at a pH below 6.0, and
subsequently readjusting the pH of the core-shell colloid to a pH between about 7-10; followed by the addition of a cross-linking reagent capable of cross-linking the polymer; and finally adjusting the pH of the colloid to approximately physiological conditions wherein the core-shell colloid contains between 10 and 30 μmol amine-monomer/m 2 core surface area.
2. The method of claim 1 wherein said polymer made from said monomer having amine functionalities comprises poly(ethylene)imine.
3. The method of claim 1 wherein the physiological conditions are pH 7.4 in 137 mM NaCl.
4. The method of claim 1 wherein the average particle size diameter of said core particles is between 1 and 500 nm.
5. The method of claim 1 wherein said polymer made from said monomer having amine functionalities is selected from the group consisting of poly(ethylene)imine, polyallylamine, chitosan, gelatin, amino-dextran, proteins, polypeptides and polylysine.
6. The method of claim 1 wherein said core-shell colloid is stable in salt solution having a concentration between about 30 mM to about 600 mM.
7. The method of claim 1 wherein greater than 70% of said polymer made from said monomer having amine functionalities is bound to said core.
8. The method of claim 1 wherein the core-shell colloid contains between 300 and 6000 μmol amine-monomer/g core particles.
9. The method of claim 1 wherein the average particle size diameter of said core particles is between 10 and 100 nm.
10. The method of claim 1 wherein said first, second and third liquid streams are brought together in a high shear mixing zone within a dispersion medium.
11. The method of claim 10 wherein said high shear mixing zone has a turnover rate of greater than 0.1 turnovers/sec.