Active agent eluting matrices with particulates
View Patent ↗The present invention is directed to polymeric matrices for the controlled release of a hydrophilic bioactive agent. Generally, the elution control matrix includes a polymeric matrix having a first polymer and a plurality of microparticles that include the hydrophilic bioactive agent. In one embodiment, the matrix includes a polymer comprising hydrophilic and hydrophobic portions. In another embodiment, the microparticles include a crosslinked hydrophilic polymer.
1. An elution control matrix for the controlled release of a hydrophilic bioactive agent, comprising a polymeric matrix comprising:
a first polymer that is hydrophobic, wherein a portion or all of the polymeric matrix is formed from the first polymer; and
a plurality of microparticles dispersed within the polymeric matrix; wherein the microparticles comprise a hydrophilic bioactive agent and crosslinked hydrophilic polymer.
2. The elution control matrix of claim 1 wherein the microparticles comprise a polypeptide.
3. The elution control matrix of claim 1 , wherein the microparticles comprises a polypeptide that is an antibody or fragment thereof.
4. The elution control matrix of claim 1 , wherein the microparticles comprises a Fab fragment.
5. The elution control matrix of claim 1 , wherein the microparticles are formed predominantly of the hydrophilic bioactive agent.
6. The elution control matrix of claim 1 wherein the first polymer is a biostable polymer.
7. The elution control matrix of claim 6 wherein the first polymer is selected from the group consisting of poly(alkyl(meth)acrylates) and poly(aromatic(meth)acrylates).
8. The elution control matrix of claim 7 wherein the first polymer comprises poly(n-butyl methacrylate).
9. The elution control matrix of claim 1 further comprising a second polymer that is biodegradable.
10. The elution control matrix of claim 1 further comprising a second polymer, wherein the weight ratio of the second polymer to the microparticles in the matrix is in the range of 0.5:1 to 1:1.
11. The elution control matrix of claim 1 wherein the crosslinked hydrophilic polymer comprises a polysaccharide.
12. The elution control matrix of claim 11 wherein the crosslinked hydrophilic polymer comprises a polysaccharide selected from the group consisting of maltodextrin and amylose.
13. The elution control matrix of claim 1 wherein the microparticles are present in the matrix in an amount in the range of 30% to 70% by weight solids.
14. The elution control matrix of claim 1 wherein the microparticles are present in the matrix in an amount in the range of 30% to 40% by weight solids.
15. The elution control matrix of claim 1 which is in the form of a coating on an implantable medical device.
16. The elution control matrix of claim 1 which is in the form of a coating on an implantable intraocular device.
17. The elution control matrix of claim 1 wherein the hydrophilic polymer is crosslinked on the surface of the particle forming a coating or shell.
18. The elution control matrix of claim 1 wherein the crosslinked hydrophilic polymer is crosslinked via polymerized groups pendent from the hydrophilic polymer.
19. The elution control matrix of claim 1 wherein the crosslinked hydrophilic polymer is crosslinked via polymerized groups pendent from the hydrophilic polymer, wherein crosslinking is performed using a polymeric polymerization initiator comprising charged groups.
20. The elution control matrix of claim 1 which is in the form of an implant.
21. The elution control matrix of claim 1 wherein the first polymer is soluble in a halogenated alkane solvent.