Amine polymer-modified nanoparticulate carriers
The invention relates to a composition comprising a colloid which is stable under physiological pH and ionic strength, said colloid comprising particles having a silica core and a shell: a) wherein said shell comprises a cross-linked poly(ethylene)imine polymer having amine functionalities; b) wherein the particles have a volume-weighted mean particle size diameter of less than 200 nm, and c) wherein greater than 50% of said polymer in the colloid is bound to the core surfaces, wherein the polymer having amine functionalities has an average molecular weight less than 100,000 g/mol, the composition has a H of between 6 and 8; and d) wherein the colloid contains between 300 and 6000 .μmol amine-monomer/g core particles.
1. A composition comprising a colloid which is stable under physiological pH and ionic strength, said colloid comprising particles having a silica core and a shell:
a) wherein said shell comprises a cross-linked poly(ethylene)imine polymer having amine functionalities;
b) wherein the particles have a volume-weighted mean particle size diameter of less than 200 nm,
c) wherein greater than 50% of said polymer in the colloid is bound to the core surfaces, wherein the polymer having amine functionalities has an average molecular weight less than 100,000 g/mol, the composition has a pH of between 6 and 8; and
d) wherein the colloid contains between 300 and 6000 μmol amine-monomer/g core particles.
2. A composition according to claim 1 wherein said volume-weighted mean particle size diameter is less than 100 nm.
3. A composition according to claim 1 wherein the standard deviation of said volume-weighted mean particle size diameter is less than the mean particle size diameter.
4. A composition according to claim 1 wherein a protective chain of polyethylene glycol is on the surface of the particle.
5. A composition according to claim 1 wherein said particles further comprise a biomedical component.
6. A composition according to claim 1 wherein said particle comprises a radiographic contrast agent.
7. A composition according to claim 1 wherein said core has a negative charge.
8. A composition according to claim 1 wherein greater than 70% of said polymer in the colloid is bound to the core surfaces.
9. A composition according to claim 1 wherein a protective chain is on the surface of said particle.
10. A composition according to claim 1 wherein said particles further comprise a biological, pharmaceutical or diagnostic component.
11. A composition according to claim 1 wherein the solids content of said colloid is between about 1 and 30% by weight.
12. A composition according to claim 1 wherein the colloid contains greater than 10 μmol amine-monomer/m 2 core particle surface area.
13. A composition according to claim 1 wherein the mean volume-weighted particle size diameter is less than 50 nm.
14. The composition of claim 1 wherein said composition has a pH of 7.4 and a Na salt concentration of 137 mM.
15. The composition of claim 1 wherein the colloid has a salt concentration of greater than 100 mM.
16. The composition of claim 1 wherein the composition is suitable for in-vivo applications.