Sustained release intraocular drug delivery systems comprising a water soluble therapeutic agent and a release modifier
A biocompatible, sustained release intraocular drug delivery system comprising a protein or polynucleotide therapeutic agent, a polymeric carrier for the therapeutic agent and a long chain fatty alcohol release modifier. The biocompatible, sustained release intraocular drug delivery system can be used to treat an ocular condition.
1. A sustained release, biodegradable intraocular implant comprising
a) about 70-85% by weight of a biodegradable polymeric carrier, wherein the biodegradable polymeric carrier is a poly-lactide-co-glycolide (PLGA) co-polymer;
b) about 10-20% by weight of a water soluble therapeutic agent, wherein the therapeutic agent is an inhibitor of vascular endothelial growth factor (VEGF) selected from the group consisting of ranibizumab, bevacizumab, mixtures of ranibizumab and bevacizumab, pegaptanib, and an siRNA molecule; and
c) about 5-10% by weight of a long chain fatty alcohol comprising from between 10 to 40 carbon atoms;
wherein a therapeutically effective amount of the therapeutic agent is released from the biodegradable intraocular implant for at least one week after the intraocular implant is placed in the eye.
2. The intraocular implant of claim 1 , wherein the long chain fatty alcohol is selected from the group consisting of capric alcohol, lauryl alcohol, myristyl alcohol, cetyl alcohol, palmitoleyl alcohol, stearyl alcohol, isostearyl alcohol, elaidyl alcohol, oleyl alcohol, linoleyl alcohol, polyunsaturated elaidolinoleyl alcohol, polyunsaturated linolenyl alcohol, elaidolinolenyl alcohol, polyunsaturated ricinoleyl alcohol, arachidyl alcohol, behenyl alcohol, erucyl alcohol, lignoceryl alcohol, ceryl alcohol, montanyl alcohol, cluytyl alcohol, myricyl alcohol, melissyl alcohol, and geddyl alcohol.
3. A method for treating an ocular condition, the method comprising the step of intraocular placement of a sustained release, biodegradable intraocular implant according to claim 1 .
4. The method of claim 3 , wherein the step of intraocular placement is carried out using an intraocular injector.
5. The method of claim 3 , wherein the ocular condition is selected from the group consisting of uveitis, macular edema, macular degeneration, proliferative retinopathy, diabetic retinopathy, retinitis pigmentosa and glaucoma.
6. The intraocular implant of claim 1 , wherein said long chain fatty alcohol is selected from the group consisting of 1-hexadecanol, 1-octadecanol, and 1-eicosanol.
7. The intraocular implant of claim 1 , wherein said long chain fatty alcohol is a saturated straight chain alcohol 16 to 26 carbon atoms in length.
8. The intraocular implant of claim 1 , wherein said long chain fatty alcohol is 1-eicosanol.