OCULAR IMPLANTS CONFIGURED TO STORE AND RELEASE STABLE DRUG FORMULATIONS
Disclosed herein are drug delivery devices and methods for the treatment of ocular disorders requiring targeted and controlled administration of a drug to an interior portion of the eye for reduction or prevention of symptoms of the disorder. In several embodiments, the devices are configured to release a pro-drug form of a drug into a target tissue site, wherein the pro-drug is converted to an active drug that yields a therapeutic effect. The use of the device and pro-drug form advantageously, in several embodiments, provide a stable drug composition that can yield a therapeutic effect over an extended time period.
1 . An ocular drug delivery implant comprising:
an outer shell defining an interior space;
at least a first drug positioned within said interior space;
wherein said outer shell includes a rate-limiting element through which said first drug is capable of eluting in a controlled fashion,
wherein said first drug is in the form of a low-activity or inactive pro-drug,
wherein upon implantation of said implant in an ocular target region, said pro-drug elutes out of said device, and
whereby upon said elution, said pro-drug form is converted to an active drug form via one or more chemical mechanisms.
2 . The implant of claim 1 , where the rate-limiting element is a hydrophobic membrane.
3 . The implant of claim 1 , wherein the implant is configured for implantation in an ocular tissue to allow elution of said pro-drug into the anterior chamber of the eye.
4 . The implant of claim 1 , wherein said pro-drug comprises a prostaglandin analog selected from the group consisting of travoprost, latanoprost, bimatoprost, and combinations thereof.
5 . The implant of claim 1 , wherein said hydrophobic polymer is selected from the group consisting of ethylene vinyl acetate, silicone, Purasil, and polyethylene.
6 . The implant of claim 1 , wherein said hydrophobic polymer is configured to prevent bulk flow of ocular fluid into said interior space.
7 . The implant of claim 1 , wherein outer shell is elongate in shape and comprises a proximal and distal end.
8 . The implant of claim 1 , wherein the amount of pro-drug within said interior space is selected such that at least about 50% of said eluted pro-drug is converted to an active drug form.
9 . The implant of claim 1 , wherein the pro-drug comprises an esterified form of an active drug.
10 . The implant of claim 1 , wherein the pro-drug requires phosphorylation or dephosphorylation to be converted into an active form.
11 . The implant of claim 1 , wherein the pro-drug requires alkylation or dealkylation to be converted into an active form.
12 . The implant of claim 1 , wherein the pro-drug requires hydrolysis to be converted into an active form.
13 . The implant of claim 1 , wherein the pro-drug within the implant results in a longer-term drug elution profile as compared to an implant loaded with an active form of the first drug.
14 . A method for treating an ocular disorder, comprising:
implanting into a target region of an eye of said subject a device comprising:
an outer shell defining an interior space;
an esterified pro-drug positioned within said interior space,
wherein said outer shell comprises a hydrophobic membrane through which said pro-drug is capable of eluting in a controlled fashion;
wherein implantation of said device results in elution of said pro-drug to said target region,
wherein elution of said pro-drug results in de-esterification of said pro-drug into an active drug, and
wherein said active drug yields a therapeutic effect, thereby treating said ocular disorder.
15 . The method of claim 14 , wherein said ocular disorder is glaucoma.
16 . The method of claim 14 , wherein said pro-drug comprises a prostaglandin analog selected from the group consisting of travoprost, latanoprost, bimatoprost, and combinations thereof.
17 . The method of claim 14 , wherein said therapeutic effect is a decrease in intraocular pressure.
18 . An ocular drug delivery implant for delivery of a drug to the anterior chamber of an eye, comprising:
an elongate outer shell having a proximal end, a distal end, said outer shell being shaped to define an interior lumen;
a pro-drug positioned within said interior lumen;
wherein, after implantation of said implant in an ocular target region, said pro-drug is capable of eluting though said elongate outer shell in a controlled fashion,
wherein upon said elution, said pro-drug form is converted to an active drug form, said active drug form resulting in a therapeutic effect.
19 . The implant of claim 18 , wherein said pro-drug comprises an esterified, phosphorylated, dephosphorylated, hydrolyzed, non-hydrolyzed, alkylated, or dealkylated form of a drug.
20 . The implant of claim 18 , wherein said pro-drug comprises a reduced activity prostaglandin analog selected from the group consisting of travoprost, latanoprost, bimatoprost, and combinations thereof.
21 . The implant of claim 18 , wherein said implant is configured for implantation in a position allowing the pro-drug to elute from the implant into the anterior chamber of an eye in order to treat increased intraocular pressure.