DRUG DELIVERY SYSTEM FOR THE DELIVERY OF ANTIVIRAL AGENTS
This invention relates to novel implant drug delivery systems for long-acting delivery of antiviral drugs. These compositions are useful for the treatment or prevention of human immunodeficiency virus (HIV) infection.
1 . An implant drug delivery system comprising a biocompatible bioerodible polymer and 4′-ethynyl-2-fluoro-2′-deoxyadenosine wherein said implant drug delivery system is implanted subdermally and 4′-ethynyl-2-fluoro-2′-deoxyadenosine is continually released in vivo at a rate resulting in a plasma concentration between 0.02 ng/mL and 300.0 ng/mL.
2 . The implant drug delivery system of claim 1 wherein the 4′-ethynyl-2-fluoro-2′-deoxyadenosine plasma concentration is between 0.02 ng/mL and 30.0 ng/mL.
3 . The implant drug delivery system of claim 2 wherein the 4′-ethynyl-2-fluoro-2′-deoxyadenosine plasma concentration is between 0.02 ng/mL and 8.0 ng/mL.
4 . The implant drug delivery system of claim 1 wherein the biocompatible bioerodible polymer is selected from the group consisting of poly(DL-lactide), poly(caprolactone), poly(lactide-co-glycolide), poly(lactide), poly(glycolide), poly(ortho esters), poly(dioxanone), poly(alkylcyanoacrylates) and combinations thereof.
5 . The implant drug delivery system of claim 4 wherein the biocompatible bioerodible polymer is poly(DL-lactide).
6 . The implant drug delivery system of claim 4 wherein the biocompatible bioerodible polymer is poly(caprolactone).
7 . The implant drug delivery system of claim 1 , further comprising a diffusional barrier.
8 . The implant drug delivery system of claim 7 , wherein the diffusional barrier is selected from the group consisting of poly(lactide-co-glycolide), poly(lactide), poly(glycolide), poly(caprolactone), poly(ortho esters), poly(dioxanone), poly(alkylcyanoacrylates) and combinations thereof.
9 . The implant drug delivery system of claim 8 , wherein the diffusional barrier comprises 4′-ethynyl-2-fluoro-2′-deoxyadenosine.
10 . The implant drug delivery system of claim 1 wherein the 4′-ethynyl-2-fluoro-2′-deoxyadenosine is dispersed or dissolved in the biocompatible bioerodible polymer.
11 . The implant drug delivery system of claim 1 wherein 4′-ethynyl-2-fluoro-2′-deoxyadenosine is present in the biocompatible bioerodible polymer at about 0.10% and 80% by weight of drug loading.
12 . The implant drug delivery system of claim 11 wherein 4′-ethynyl-2-fluoro-2′-deoxyadenosine is present in the biocompatible bioerodible polymer at 30% and 65% by weight of drug loading.
13 . The implant drug delivery system of claim 11 wherein 4′-ethynyl-2-fluoro-2′-deoxyadenosine is present in the biocompatible bioerodible polymer at 40% and 45% by weight of drug loading.
14 . The implant drug delivery system of claim 1 comprising between 1% and 20% by weight of a radiopaque material.
15 . The implant drug delivery system of claim 1 wherein the 4′-ethynyl-2-fluoro-2′-deoxyadenosine is released at therapeutic concentrations for a duration from between three months and thirty-six months.
16 . The implant drug delivery system of claim 1 wherein the 4′-ethynyl-2-fluoro-2′-deoxyadenosine is released at prophylactic concentrations for a duration from between three months and thirty-six months.
17 . A method of treating or preventing HIV infection with an implant drug delivery system according to claim 1 .
18 . The implant drug delivery system of claim 1 wherein one or more implants can be used to achieve the desired therapeutic dose for durations up to 1 year.
19 . The implant drug delivery system of claim 1 wherein one or more implants can be used to achieve the desired therapeutic dose for durations up to 2 years.