DRUG DELIVERY DEVICES, KITS AND METHODS THEREFOR

• US 20090196903A1
• Filed: 01/29/2009
• Published: 08/06/2009
• Est. Priority Date: 01/29/2008
• Status: Active Grant

• Current Assignee: Microchips Biotech, Inc. (Keratin Biosciences, Inc.)
• Original Assignee: Gilbert H. Kliman
• Inventors: KLIMAN, Gilbert H.
• Granted Patent: US 8,521,273 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61P 27/02 Ophthalmic agents

Abstract

Implantable drug delivery devices, and kits and methods incorporating them are described. The devices may, for example, be configured for implantation into an ocular region of a subject. The drug delivery devices may comprise multiple, selectively-triggerable drug reservoirs for administration of sequential or concomitant drug regimens. Some variations of devices may comprise one or more reservoirs that may be triggered by an optical stimulus, e.g., light having a wavelength within a certain wavelength range. The devices, methods, and kits may be useful in the treatment chronic ocular conditions, such as age-related macular degeneration.

Claims

1. A drug delivery device for implantation into a subject, the device comprising:

a first reservoir configured to be loaded with a first agent; and

a first target region configured to selectively absorb light from a first optical stimulus to trigger release of the first agent, the first optical stimulus comprising light having a wavelength within a first wavelength range.

2. The drug delivery device of claim 1, wherein the first wavelength range is between about 500 nm to about 1500 nm.

3. The drug delivery device of claim 2, wherein the first wavelength range is between about 500 nm to about 700 nm.

4. The drug delivery device of claim 3, wherein the first wavelength range is between about 500 nm to about 600 nm.

5. The drug delivery device of claim 1, wherein the first wavelength range overlaps with emission from the group consisting of an argon ion laser, a Nd:

YAG laser, a frequency-doubled Nd;

YAG laser, a diode laser, a Nd;

YLF laser, a krypton laser, a dye laser, and a helium-neon laser.

6. The drug delivery device of claim 1, wherein the first target region comprises a chromophore selected to absorb light emitted over the first wavelength range.

7. The drug delivery device of claim 1, comprising a second reservoir that is configured to be loaded with a second agent and to release the second agent.

8. The drug delivery device of claim 7, wherein the second reservoir is configured to release the second agent loaded therein in response to a second stimulus.

9. The drug delivery device of claim 8, wherein the second stimulus comprises a second optical stimulus.

10. The drug delivery device of claim 8, wherein the second stimulus comprises a stimulus selected from the group consisting of a thermal stimulus, a radiofrequency stimulus, an ionizing radiative stimulus, an electrical stimulus, a mechanical stimulus, a chemical stimulus, an ultrasound stimulus, a magnetic stimulus, and combinations thereof.

11. The drug delivery device of claim 7, wherein the first and second agents are the same.

12. The drug delivery device of claim 7, wherein the first and second agents are different.

13. The drug delivery device of claim 9, wherein the second optical stimulus is different than the first optical stimulus.

14. The drug delivery device of claim 13, wherein the first optical stimulus comprises irradiation of the device with a first wavelength and the second optical stimulus comprises irradiation of the device with a second wavelength.

15. The drug delivery device of claim 13, wherein the first optical stimulus comprises irradiation of the device with a first power density and the second optical stimulus comprises irradiation of the device with a second power density.

16. The drug delivery device of claim 13, wherein the first optical stimulus comprises irradiation of the device with an incident beam having a first spot size and the second optical stimulus comprises irradiation of the device with an incident beam having a second spot size.

17. The drug delivery device of claim 13, wherein the first optical stimulus comprises irradiation of the device with an incident beam having a first spot geometry and the second optical stimulus comprises irradiation of the device with an incident beam having a second spot geometry.

18. The drug delivery device of claim 9, wherein the second reservoir comprises a second target region configured to interact with the second optical stimulus to trigger release of the agent loaded in the second reservoir.

19. The drug delivery device of claim 14, wherein the first reservoir comprises a first chromophore that absorbs the first wavelength, and the second reservoir comprises a second chromophore that absorbs the second wavelength.

20. The drug delivery device of claim 1, wherein the first optical stimulus triggers formation of a first orifice in the first reservoir.

21. The drug delivery device of claim 20, wherein the first reservoir is configured to release the first agent through the first orifice via diffusion into the anatomy of the subject.

22. The drug delivery device of claim 20, wherein the first reservoir is configured to release the first agent in a sustained manner after the formation of the first orifice.

23. The drug delivery device of claim 1, wherein the first reservoir comprises an active mechanism configured to actively release the first agent following triggering.

24. The drug delivery device of claim 23, wherein the active mechanism comprises a pump or injector.

25. The drug delivery device of claim 1, wherein the first reservoir is configured to passively release the first agent following triggering.

26. The drug delivery device of claim 1, further comprising a coating.

27. The drug delivery device of claim 26, wherein the coating is configured to passively release an agent.

28. The drug delivery device of claim 1, wherein the first reservoir is configured to change shape in response to the first optical stimulus.

29. The drug delivery device of claim 28, wherein the shape change causes the first reservoir to release the first agent in a sustained manner into the anatomy of the subject.

30. The drug delivery device of claim 1, configured to be implanted in an ocular region of the subject.

31. The drug delivery device of claim 7, wherein the first and second reservoirs are interconnected.

32. The drug delivery device of claim 7, comprising first and second device body sections configured to move independently of each other, wherein the first device body section comprises the first reservoir and the second device body section comprises the second reservoir.

33. The drug delivery device of claim 1, further comprising a tether configured to allow retrieval of the device, repositioning of the device, and/or securing of the device.

34. The drug delivery device of claim 1, further comprising an attachment configured to allow the device to be secured to the subject'"'"'s anatomy.

35. The drug delivery device of claim 7, wherein at least one of the first and second agents is selected from the group consisting of:

anti-inflammatories, anti-infectives, anti-allergens, cholinergic agonists and antagonists, adrenergic agonists and antagonists, anti-glaucoma agents, agents for cataract prevention or treatment, neuroprotection agents, anti-oxidants, antihistamines, anti-platelet agents, anti-coagulants, anti-thrombic agents, anti-scarring agents, anti-proliferatives, anti-tumor agents, complement inhibitors, decongestants, vitamins, growth factors, anti-growth factor agents, gene therapy vectors, chemotherapy agents, protein kinase inhibitors, small interfering RNAs, limus family compounds, and combinations thereof.

36. The drug delivery device of claim 35, wherein at least one of the first and second agents comprises an anti-growth factor agent.

37. The drug delivery device of claim 36, wherein the anti-growth factor agent comprises an anti-VEGF agent.

38. The drug delivery device of claim 36, wherein the anti-VEGF agent comprises aflibercept.

39. The drug delivery device of claim 36, wherein the anti-VEGF agent comprises ranibizumab.

40. The drug delivery device of claim 36, wherein the anti-VEGF agent comprises bevacizumab.

41. The drug delivery device of claim 35, wherein at least one of the first and second agents comprises an anti-inflammatory agent.

42. The drug delivery device of claim 41, wherein the anti-inflammatory agent comprises a steroidal agent.

43. The drug delivery device of claim 42, wherein the steroidal agent comprises dexamethasone.

44. The drug delivery device of claim 42, wherein the steroidal agent comprises triamcinolone.

45. The drug delivery device of claim 42, wherein the steroidal agent comprises fluocinolone.

46. The drug delivery device of claim 35, wherein at least one of the first and second agents comprises a limus family compound.

47. The drug delivery device of claim 46, wherein the limus family compound comprises rapamycin.

48. The drug delivery device of claim 35, wherein at least one of the first and second agents comprises a complement inhibitor.

49. The drug delivery device of claim 7, wherein the first and second agents are selected to be part of a concomitant combination drug regimen.

50. The drug delivery device of claim 7, wherein the first and second agents are selected to be part of a sequential drug regimen.

51. The drug delivery device of claim 1, wherein the drug delivery device comprises a first delivery configuration and a second implanted configuration.

52. The drug delivery device of claim 51, wherein the first delivery configuration is configured to be implanted in the subject through a 20 gauge or smaller cannula.

53. The drug delivery device of claim 51, wherein the first delivery configuration is elongated, and the second implanted configuration comprises at least one curve.

54. The drug delivery device of claim 51, wherein the first delivery configuration comprises at least one fold.

55. The drug delivery device of claim 1, configured for the treatment of age-related macular degeneration.

56. The drug delivery device of claim 1, wherein the device is configured to receive a replacement reservoir comprising the first agent.

57. The drug delivery device of claim 56, wherein the replacement reservoir is pre-loaded with the first agent.

58. The drug delivery device of claim 7, wherein at least one of the first and second reservoirs is configured to be loaded with its respective agent while the device is implanted in the subject.

59. The drug delivery device of claim 7 wherein at least one of the first and second reservoirs is configured to be reloaded with a reload agent.

60. The drug delivery device of claim 49, wherein the reload agent is contained in a pre-loaded replacement reservoir.

61. The drug delivery device of claim 1, comprising a third reservoir that is configured to be loaded with a third agent.

62. The drug delivery device of claim 61, wherein the third reservoir is configured to release the third agent in response to a third stimulus.

63. The drug delivery device of claim 30, configured to be implanted in a vitreous cavity, a retina, a sclera, a cornea, or a conjunctiva of the subject.

109. A drug delivery implant comprising a proximal end, a distal end, a housing extending therebetween, and the drug delivery device of claim 1 configured to be received within the housing.

110. The drug delivery implant of claim 109, wherein the proximal end comprises an access area.

111. The drug delivery implant of claim 109, wherein the implant has a circular, ellipsoidal, or quadrilateral cross-sectional geometry.

112. The drug delivery implant of claim 109, configured to be implanted in an ocular region of a subject.

113. The drug delivery implant of claim 112, wherein the ocular region is a vitreous cavity, a retina, a sclera, a cornea, a conjunctiva, or a potential space within the orbit.

114. The drug delivery implant of claim 109, wherein the implant comprises a transparent material.

115. The drug delivery implant of claim 114, wherein the transparent material comprises a transparent polymer.

116. The drug delivery implant of claim 115, wherein the transparent polymer comprises an acrylic copolymer, acrylonitrile butadiene styrene (ABS), polycarbonate, polystyrene, polyvinyl chloride (PVC), polyethylene terephthalate glycol (PETG), or styrene acrylonitrile (SAN).

117. The drug delivery implant of claim 116, wherein the acrylic copolymer comprises polymethyl methacrylate (PMMA) copolymer or styrene methyl methacrylate (SMMA) copolymer.

118. The drug delivery implant of claim 109, wherein the implant comprises one or more windows.

119. The drug delivery implant of claim 109, further comprising a fixation element.

120. The drug delivery implant of claim 109, wherein the proximal end comprises a sealing valve.

121. The drug delivery implant of claim 109, wherein the first agent is selected from the group consisting of anti-inflammatories, anti-infectives, anti-allergens, cholinergic agonists and antagonists, adrenergic agonists and antagonists, anti-glaucoma agents, agents for cataract prevention or treatment, neuroprotection agents, anti-oxidants, antihistamines, anti-platelet agents, anti-coagulants, anti-thrombic agents, anti-scarring agents, anti-proliferatives, anti-tumor agents, complement inhibitors, decongestants, vitamins, growth factors, anti-growth factor agents, gene therapy vectors, chemotherapy agents, protein kinase inhibitors, small interfering RNAs, limus family compounds, and combinations thereof.

122. The drug delivery implant of claim 121, wherein the first agent comprises an anti-growth factor agent.

123. The drug delivery implant of claim 122, wherein the anti-growth factor agent comprises an anti-VEGF agent.

124. The drug delivery implant of claim 123, wherein the anti-VEGF agent comprises aflibercept.

125. The drug delivery implant of claim 123, wherein the anti-VEGF agent comprises ranibizumab.

126. The drug delivery implant of claim 123, wherein the anti-VEGF agent comprises bevacizumab.

127. The drug delivery implant of claim 121, wherein the first agent comprises an anti-inflammatory agent.

128. The drug delivery implant of claim 127, wherein the anti-inflammatory agent comprises a steroidal agent.

129. The drug delivery implant of claim 128, wherein the steroidal agent comprises dexamethasone.

130. The drug delivery implant of claim 128, wherein the steroidal agent comprises triamcinolone.

131. The drug delivery implant of claim 128, wherein the steroidal agent comprises fluocinolone.

132. The drug delivery implant of claim 121, wherein the first agent comprises a limus family compound.

133. The drug delivery implant of claim 132, wherein the limus family compound comprises rapamycin.

134. The drug delivery implant of claim 133, wherein the first agent comprises a complement inhibitor.

64. A kit comprising:

a drug delivery device for implantation into a subject, the device comprising;

a first reservoir configured to be loaded with a first agent; and

a first target region configured to selectively absorb light from a first optical stimulus to trigger release of the first agent; and

an implantation device configured to implant the drug delivery device into the subject.

65. The kit of claim 64, further comprising a first optical source configured to deliver the first optical stimulus to the first target region.

66. The kit of claim 65, wherein the first optical source is selected from the group consisting of:

an argon ion laser, a Nd;

YAG laser, a frequency-doubled Nd;

YAG laser, a diode laser, a Nd;

YLF laser, a helium-neon laser, a krypton ion laser, and a dye laser.

67. The kit of claim 65, wherein the first optical source emits pulsed light.

68. The kit of claim 65, comprising at least one focusing apparatus to adjust a power density of light emitted from the first optical source.

69. The kit of claim 68, wherein the at least one focusing apparatus comprises a lens.

70. The kit of claim 64, wherein the implantation device comprises a 20 gauge or smaller cannula.

71. A kit comprising:

a first drug delivery device for implantation into a subject, the device comprising;

a first reservoir configured to be loaded with a first agent; and

a first target region configured to selectively absorb light from a first optical stimulus to trigger release of the first agent; and

a second drug delivery device for implantation into a subject.

72. A kit comprising:

a first agent; and

a first drug delivery device for implantation into a subject, the device comprising;

a first reservoir configured to be loaded with the first agent; and

a first target region configured to selectively absorb light from a first optical stimulus to trigger release of the first agent.

73. The kit of claim 72, comprising a suite of agents comprising at least the first agent.

74. The kit of claim 72, comprising a first replacement reservoir configured to be loaded with the first agent, wherein the first drug delivery device is configured to receive the first replacement reservoir.

75. A method comprising:

implanting a drug delivery device into the anatomy of a subject, the drug delivery device comprising;

a first reservoir loaded with a first agent; and

a first target region configured to selectively absorb light from a first optical stimulus, the first optical stimulus comprising light within a first wavelength range; and

irradiating the first target region with the first optical stimulus to trigger release of the first agent.

76. The method of claim 75, wherein the drug delivery device comprises a second reservoir loaded with a second agent.

77. The method of claim 76, comprising triggering release of the second agent with a second stimulus.

78. The method of claim 77, wherein the second stimulus comprises a second optical stimulus.

79. The method of claim 77, wherein the second stimulus is selected from the group consisting of a thermal stimulus, a chemical stimulus, an electrical stimulus, an ultrasound stimulus, a magnetic stimulus, a mechanical stimulus, a radiofrequency stimulus, an ionizing radiative stimulus, and combinations thereof.

80. The method of claim 78, wherein the second optical stimulus comprises irradiation of the second reservoir with light having a different wavelength than the first optical stimulus.

81. The method of claim 78, wherein the second optical stimulus comprises irradiation of the second reservoir with light having a different power density than the first optical stimulus.

82. The method of claim 78, wherein the second optical stimulus comprises irradiation of the second reservoir with an incident beam having a different spot size than the first optical stimulus.

83. The method of claim 78, wherein the second optical stimulus comprises irradiation of the second reservoir with an incident beam having a different spot geometry than the first optical stimulus.

84. The method of claim 76, comprising releasing the first and second agents to provide a combination drug regimen.

85. The method of claim 77, comprising delivering the first optical stimulus and the second stimulus to the drug delivery device in sequence.

86. The method of claim 77, comprising delivering the first optical stimulus and the second stimulus to the drug delivery device in parallel.

87. The method of claim 76, comprising delivering sequential doses of the same agent to the subject.

88. The method of claim 75, comprising implanting the drug delivery device into the anatomy of the patient with a 20 gauge or smaller cannula.

89. The method of claim 75, comprising reloading at least one of the first and second reservoirs with a reload agent after the device has been implanted into the anatomy of the subject.

90. The method of claim 75, comprising implanting the drug delivery device into an ocular region of the subject.

91. The method of claim 90, wherein the ocular region comprises a vitreous cavity, a retina, a sclera, a cornea, or a conjunctiva of the subject.

92. The method of claim 91, comprising implanting the drug delivery device into a vitreous cavity of the subject through an implantation site under a conjunctiva and sealing the implantation site after implantation by closing the conjunctiva over the implantation site.

93. The method of claim 75, wherein the first reservoir is configured for sustained release of the first agent.

94. The method of claim 75, wherein the first reservoir is configured for controlled release of the first agent.

95. The method of claim 75, wherein the first reservoir is configured for burst release of the first agent.

96. The method of claim 75, wherein the first reservoir is configured for bolus release of the first agent.

97. The method of claim 75, for treating a condition selected from the group consisting of age-related macular degeneration, diabetic retinopathy, cancer, glaucoma, retinal and choroidal disease, cataracts, dry eye syndrome, optic neuropathy, orbital disease, corneal conditions, and uveitis.

98. The method of claim 75, wherein the condition is age-related macular degeneration.

99. The method of claim 97, wherein the condition is diabetic retinopathy.

100. The method of claim 97, wherein the condition is retinal and choroidal disease.

101. The method of claim 97, wherein the condition is uveitis.

102. The method of claim 97, wherein the condition is glaucoma.

103. A method comprising:

implanting a drug delivery device into the anatomy of a subject, the drug delivery device comprising;

a first reservoir configured to be loaded with a first agent; and

a first target region configured to selectively absorb light having a wavelength within a first wavelength range to trigger release of the first agent,

loading the first reservoir with the first agent; and

irradiating the first target region with light having a wavelength within the first wavelength range.

104. The method of claim 103, comprising implanting a sealable port near that allows access to the drug delivery device after it has been implanted.

105. The method of claim 103, comprising loading the first reservoir with the first agent after implanting the drug delivery device into the anatomy of the subject.

106. A method comprising:

implanting a drug delivery device into a subject, the drug delivery device comprising first and second reservoirs, each reservoir configured to be loaded with an agent, and the first and second reservoirs comprising first and second target regions, respectively; and

visually differentiating the first reservoir from the second reservoir using the first and second target regions.

107. A drug delivery device for implantation into a subject, the device comprising:

a first reservoir configured to be loaded with a first agent, the first reservoir comprising a first target region; and

a second reservoir configured to be loaded with a second agent, the second reservoir comprising a second target region, wherein the first and second target regions are configured to be visually differentiated.

108. A drug delivery device for implantation into a subject, the device comprising:

a first reservoir configured to be loaded with a first agent, and

a first target region configured to selectively respond to a first stimulus to trigger release of the first agent from the first reservoir, wherein the first target region extends circumferentially around a body of the device.