Implant compositions for the unidirectional delivery of therapeutic compounds to the brain
The present invention provides, in some aspects, bilayered and trilayered pharmaceutical implant compositions for the unidirectional delivery of anti-cancer compounds to the brain over a period of time (e.g., several weeks, 1, 2, 3, 4, 5, 6, 7 days, or 1, 2, 3, weeks, or any range derivable therein) following the removal of glioblastoma multiforme or other malignant tumors in the brain.
1. A method of treating a brain cancer in a mammalian subject, comprising administering into a resection cavity in the brain of the subject an implant comprising at least two layers, a drug-containing layer having a drug elution surface to be positioned proximal to the tissue, and, a further layer or layers comprising a lipophilic backing layer and/or a hydrophobic coating, said further layer or layers being positioned distal to the drug elution surface, wherein:
a) the drug-containing layer comprises one or more drugs, a hydrophilic polymer or pore forming agent, and glyceryl behenate;
b) the lipophilic backing layer comprises glyceryl behenate; and
c) the hydrophobic coating comprises glyceryl behenate and coats surfaces of the implant that are not to be positioned proximal to the tissue; and
further, when each of layers a), b) and c) are present, the lipophilic backing layer is positioned between the drug-containing layer and the hydrophobic coating; and
wherein the drug elution surface is positioned proximal to the resection cavity, and, the further layer or layers comprising the lipophilic backing layer and/or the hydrophobic coating are positioned distal and/or lateral to the drug elution surface.
2. The method of claim 1 , wherein the subject is a mammal.
3. The method of claim 2 , wherein the mammal is a human.
4. The method of claim 1 , further comprising removing part or all of a tumor from the subject via the resection cavity.
5. The method of claim 4 , wherein the tumor is cancerous.
6. The method of claim 5 , wherein the tumor is a glioblastoma or glioblastoma multiforme.
7. The method of claim 5 , wherein the tumor is a high grade intrinsic brain tumor.
8. The method of claim 4 , wherein the cancer is a metastatic cancer.
9. The method of claim 1 , wherein the surface of the resection cavity or at least of the part the resection cavity is filled with a surgical glue or a fibrin glue.
10. The method of claim 9 , wherein the resection cavity is filled with a surgical glue.
11. The method of claim 9 , wherein the surgical glue is a fibrin glue.
12. The method of claim 1 , wherein part of the implant is covered with a biocompatible, biodegradable surgical fabric.
13. The method of claim 1 , wherein the brain cancer is glioblastoma or glioblastoma multiforme.