Active drug delivery in the gastrointestinal tract

• US 20040267240A1
• Filed: 05/03/2004
• Published: 12/30/2004
• Est. Priority Date: 01/29/2003
• Status: Abandoned Application

• Current Assignee: Daniel Goldstein, Yoram Sela, Yossi Gross, Ziv Belsky
• Original Assignee: Daniel Goldstein, Yoram Sela, Yossi Gross, Ziv Belsky
• Inventors: Gross, Yossi, Sela, Yoram, Belsky, Ziv, Goldstein, Daniel
• Application Number:
  US10/838,072
• Publication Number:
  US 20040267240A1
• Time in Patent Office: Days
• US Class Current: 604/890.1
• CPC Class Codes: A61B 1/041 Capsule endoscopes for imaging
• CPC Class Codes: A61B 5/0008 Temperature signals
• CPC Class Codes: A61B 5/01 Measuring temperature of body parts ; Diagnostic temperature sensing, e.g. for malignant or inflamed tissue clinical contact thermometers G01K13/20
• CPC Class Codes: A61B 5/073 Intestinal transmitters
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/42 Detecting, measuring or recording for evaluating the gastrointestinal, the endocrine or the exocrine systems A61B1/00, A61B5/4857, A61B5/486, A61B5/4866, A61B5/4869 take precedence
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61J 3/07 into the form of capsules or similar small containers for oral use
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/0097 Micromachined devices; Microelectromechanical systems [MEMS]; Devices obtained by lithographic treatment of silicon; Devices comprising chips intradermal microneedle arrays A61K9/0021; MEMS in general B81B7/02
• CPC Class Codes: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50

Abstract

Apparatus for drug administration is provided, including an ingestible capsule, which includes a drug, stored by the capsule, and an environmentally-sensitive mechanism, adapted to change a state thereof responsively to a disposition of the capsule within a gastrointestinal (GI) tract of a subject. The capsule further includes first and second electrodes, and a control component, adapted to facilitate passage of the drug, in response to a change of state of the environmentally-sensitive mechanism, through an epithelial layer of the GI tract by driving the first and second electrodes to apply a “low intensity time-varying” (LITV) signal.

Claims

1. Apparatus for drug administration, comprising an ingestible capsule, which comprises:

a drug, stored by the capsule;

an environmentally-sensitive mechanism, adapted to change a state thereof responsively to a disposition of the capsule within a gastrointestinal (GI) tract of a subject;

first and second electrodes; and

a control component, adapted to facilitate passage of the drug, in response to a change of state of the environmentally-sensitive mechanism, through an epithelial layer of the GI tract by driving the first and second electrodes to apply a “

low intensity time-varying”

(LITV) signal.

2. The apparatus according to claim 1, wherein the LITV signal includes a signal that creates a field that is less than about 5 Volts/cm and varies at a rate greater than about 1 Hz, and wherein the control component is adapted to drive the first and second electrodes to apply the signal that creates the field.

3. The apparatus according to claim 1, wherein the LITV signal includes a signal capable of opening tight junctions of the epithelial layer to an extent sufficient to allow at least a 100% increase in passage of the drug therethrough, and wherein the control component is adapted to drive the first and second electrodes to apply the signal capable of opening the tight junctions.

4. The apparatus according to claim 1, wherein the LITV signal includes a signal insufficient to cause electroporation of cells of the epithelial layer, and wherein the control component is adapted to drive the first and second electrodes to apply the signal that is insufficient to cause the electroporation.

5. The apparatus according to claim 1,

wherein the environmentally-sensitive mechanism comprises a sensor adapted to sense an indication of a distance traveled by the capsule in the GI tract, and

wherein the environmentally-sensitive mechanism is adapted to undergo the change of state responsive to the distance.

6. The apparatus according to claim 1, wherein the environmentally-sensitive mechanism comprises a camera, adapted to image the GI tract, and wherein the control component is adapted to drive the first and second electrodes to apply the LITV signal in response to an image acquired by the camera.

7. The apparatus according to claim 1, wherein the disposition of the capsule includes a temperature in a vicinity of the capsule, wherein the environmentally-sensitive mechanism comprises a temperature sensor, and wherein the control component is adapted to drive the first and second electrodes to apply the LITV signal in response to the temperature sensed by the temperature sensor.

8. The apparatus according to claim 1, wherein the disposition of the capsule includes a pH in a vicinity of the capsule, wherein the environmentally-sensitive mechanism comprises a pH sensor, and wherein the control component is adapted to drive the first and second electrodes to apply the LITV signal in response to the pH sensed by the pH sensor.

9. The apparatus according to claim 1, wherein the environmentally-sensitive mechanism comprises a sensor, adapted to sense a characteristic of the GI tract, and wherein the control component is adapted to drive the first and second electrodes to apply the LITV signal in response to the sensed characteristic.

10. The apparatus according to claim 1, wherein the control component is adapted to:

drive the first and second electrodes to apply the LITV signal, and

drive an iontophoretic current between the first and second electrodes.

11. The apparatus according to claim 1, wherein the control component is adapted to configure the LITV signal using parameters selected at least in part responsively to the disposition of the capsule within the GI tract.

12. The apparatus according to claim 1, wherein the control component is adapted to configure the LITV signal using parameters selected at least in part responsively to a property of the drug.

13. The apparatus according to claim 1, wherein the control component is adapted to drive the first and second electrodes to apply the LITV signal at a current of less than about 5 mA.

14. The apparatus according to claim 1, wherein the control component is adapted to drive the first and second electrodes to apply the LITV signal for a period of between about 1 and about 120 minutes.

15. The apparatus according to claim 1, wherein the control component is adapted to configure the LITV signal to be sufficiently weak so as not to cause local activation of smooth muscle.

16. The apparatus according to claim 1, wherein the capsule comprises a central portion, intermediate the first and second electrodes, a shape of the central portion being such as to reduce current flow within a lumen of the GI tract.

17. The apparatus according to claim 1, wherein the capsule comprises a central portion, intermediate the first and second electrodes, the central portion having a diameter that is such as to bring the central portion in contact with the epithelial layer of the GI tract, whereby to reduce current flow within a lumen of the GI tract.

18. The apparatus according to claim 1, wherein the capsule comprises a self-expansible central portion, intermediate the first and second electrodes, the central portion adapted to expand, in response to being in the GI tract, to have a diameter that is such as to bring the central portion in contact with the epithelial layer of the GI tract, whereby to reduce current flow within a lumen of the GI tract.

19. The apparatus according to claim 1, wherein the capsule comprises a central portion, intermediate the first and second electrodes, an outer surface of the central portion comprising a hydrophobic material.

20. The apparatus according to claim 1, wherein the capsule comprises a central portion, intermediate the first and second electrodes, an outer surface of the central portion comprising a lipophilic material.

21. The apparatus according to claim 1, wherein the environmentally-sensitive mechanism is essentially entirely biodegradable.

22. The apparatus according to claim 1, wherein the first and second electrodes and the control component are essentially entirely biodegradable.

23. The apparatus according to claim 1, wherein at least 80% of the mass of the capsule is biodegradable.

24. The apparatus according to claim 23, wherein at least 95% of the mass of the capsule is biodegradable.

25. The apparatus according to claim 24, wherein essentially the entire capsule is biodegradable.

26. The apparatus according to claim 1, wherein the environmentally-sensitive mechanism comprises a coating on a surface of the capsule.

27. The apparatus according to claim 26, wherein the coating comprises a pH-sensitive coating.

28. The apparatus according to claim 1, wherein the control component is adapted to configure the LITV signal to include a series of pulses.

29. The apparatus according to claim 28, wherein the control component is adapted to drive the first and second electrodes to apply the LITV signal at a current of less than about 5 mA.

30. The apparatus according to claim 28, wherein the control component is adapted to configure the LITV signal to have a frequency of between about 1 and about 100 Hz.

31. The apparatus according to claim 28, wherein the control component is adapted to configure the LITV signal to have a pulse duration of between about 0.1 and about 10 milliseconds.

32. The apparatus according to claim 28, wherein the control component is adapted to:

drive the first and second electrodes to apply the LITV signal at a current of less than about 5 mA, and

configure the LITV signal to have a frequency of between about 1 and about 100 Hz, and a pulse duration of between about 0.1 and about 10 milliseconds.

33. The apparatus according to claim 28, wherein the control component is adapted to drive the first and second electrodes to apply the LITV signal at a voltage per centimeter of between about 0.5 and about 5 Volts/cm.

34. The apparatus according to claim 1, wherein the control component is adapted to drive the first and second electrodes to apply the LITV signal in a train of bursts, each of the bursts including at least one pulse.

35. The apparatus according to claim 34, wherein the control component is adapted to configure the train to have a repetition frequency of between about 6 and about 30 Hz.

36. The apparatus according to claim 34, wherein the control component is adapted to configure each of the bursts to include between 1 and about 4 pulses.

37. The apparatus according to claim 34, wherein the control component is adapted to configure each of the bursts to include a plurality of pulses, having a delay of about 4 to about 8 milliseconds between the start of each successive pulse.

38. The apparatus according to claim 34, wherein the control component is adapted to configure the at least one pulse to have a duration of between about 0.1 and about 2 milliseconds.

39. Apparatus for administration of a drug, comprising an ingestible capsule adapted to store the drug, the capsule comprising:

an environmentally-sensitive mechanism, adapted to change a state thereof responsively to a disposition of the capsule within a gastrointestinal (GI) tract of a subject;

first and second electrodes; and

a control component, adapted to facilitate passage of the drug, in response to a change of state of the environmentally-sensitive mechanism, through an epithelial layer of the GI tract by driving the first and second electrodes to apply a “

low intensity time-varying”

(LITV) signal.

40. The apparatus according to claim 39, wherein the LITV signal includes a signal that creates a field that is less than about 5 Volts/cm and varies at a rate greater than about 1 Hz, and wherein the control component is adapted to drive the first and second electrodes to apply the signal that creates the field.

41. The apparatus according to claim 39, wherein the LITV signal includes a signal capable of opening tight junctions of the epithelial layer to an extent sufficient to allow at least a 100% increase in passage of the drug therethrough, and wherein the control component is adapted to drive the first and second electrodes to apply the signal capable of opening the tight junctions.

42. The apparatus according to claim 39, wherein the LITV signal includes a signal insufficient to cause electroporation of cells of the epithelial layer, and wherein the control component is adapted to drive the first and second electrodes to apply the signal that is insufficient to cause the electroporation.

43. Apparatus for drug administration, comprising an ingestible capsule, which comprises:

a drug, stored by the capsule;

an environmentally-sensitive mechanism, adapted to change a state thereof responsively to a disposition of the capsule within a gastrointestinal (GI) tract of a subject;

first and second electrodes; and

a control component, adapted to facilitate passage of the drug, in response to a change of state of the environmentally-sensitive mechanism, through an epithelial layer of the GI tract by driving an electroporation current between the first and second electrodes.

44. The apparatus according to claim 43, wherein the control component is adapted to configure the electroporation current to have an AC voltage of between about 3 and about 50 Volts.

45. The apparatus according to claim 43, wherein the control component is adapted to configure the electroporation current to have a frequency of between about 1 and about 300 Hz.

46. The apparatus according to claim 43, wherein the control component is adapted to:

drive the electroporation current between the first and second electrodes, and

drive an iontophoretic current between the first and second electrodes.

47. The apparatus according to claim 43, wherein the control component is adapted to configure the electroporation current using parameters selected at least in part responsively to the disposition of the capsule within the GI tract.

48. The apparatus according to claim 43, wherein the control component is adapted to configure the electroporation current using parameters selected at least in part responsively to a property of the drug.

49. The apparatus according to claim 43, wherein the environmentally-sensitive mechanism is essentially entirely biodegradable.

50. The apparatus according to claim 43, wherein the first and second electrodes and the control component are essentially entirely biodegradable.

51. The apparatus according to claim 43, wherein at least 80% of the mass of the capsule is biodegradable.

52. The apparatus according to claim 51, wherein at least 95% of the mass of the capsule is biodegradable.

53. The apparatus according to claim 52, wherein essentially the entire capsule is biodegradable.

54. Apparatus for administration of a drug, comprising an ingestible capsule adapted to store the drug, the capsule comprising:

an environmentally-sensitive mechanism, adapted to change a state thereof responsively to a disposition of the capsule within a gastrointestinal (GI) tract of a subject;

first and second electrodes; and

a control component, adapted to facilitate passage of the drug, in response to a change of state of the environmentally-sensitive mechanism, through an epithelial layer of the GI tract by driving an electroporation current between the first and second electrodes.

55. Apparatus for drug administration, comprising an ingestible capsule, which comprises:

a drug, stored by the capsule;

an environmentally-sensitive mechanism, adapted to change a state thereof responsively to a target location of the capsule within a gastrointestinal (GI) tract of a subject;

first and second electrodes; and

a control component, adapted to;

in response to a change of state of the environmentally-sensitive mechanism, facilitate passage of the drug through an epithelial layer of the GI tract by driving a current between the first and second electrodes, and

configure the current using parameters selected at least in part responsively to the target location of the capsule within the GI tract.

56. The apparatus according to claim 55, wherein the control component is adapted to directly drive the drug through the epithelial layer by driving the current between the first and second electrodes.

57. The apparatus according to claim 55, wherein the control component is adapted to configure the current using parameters selected at least in part responsively to a property of the drug.

58. The apparatus according to claim 55, wherein the control component is adapted to configure the current to include a “

low intensity time-varying”

(LITV) signal.

59. The apparatus according to claim 55, wherein the control component is adapted to configure the current to include an electroporation current.

60. The apparatus according to claim 55, wherein the control component is adapted to configure the current to include an iontophoretic current.

61. Apparatus for administration of a drug, comprising an ingestible capsule adapted to store the drug, the capsule comprising:

an environmentally-sensitive mechanism, adapted to change a state thereof responsively to a target location of the capsule within a gastrointestinal (GI) tract of a subject;

first and second electrodes; and

a control component, adapted to;

in response to a change of state of the environmentally-sensitive mechanism, facilitate passage of the drug through an epithelial layer of the GI tract by driving a current between the first and second electrodes, and

configure the current using parameters selected at least in part responsively to the target location of the capsule within the GI tract.

62. Apparatus for drug administration, comprising an ingestible capsule, which comprises:

a drug, stored by the capsule;

an environmentally-sensitive mechanism, adapted to change a state thereof responsively to a target location of the capsule within a gastrointestinal (GI) tract of a subject;

first and second electrodes; and

a control component, adapted to;

in response to a change of state of the environmentally-sensitive mechanism, facilitate passage of the drug through an epithelial layer of the GI tract by driving a current between the first and second electrodes, and

configure the current using parameters selected at least in part responsively to a property of the drug.

63. The apparatus according to claim 62, wherein the control component is adapted to directly drive the drug through the epithelial layer by driving the current between the first and second electrodes.

64. The apparatus according to claim 62, wherein the control component is adapted to configure the current using parameters selected at least in part responsively to the target location of the capsule within the GI tract.

65. The apparatus according to claim 62, wherein the control component is adapted to configure the current to include a “

low intensity time-varying”

(LITV) signal.

66. The apparatus according to claim 62, wherein the control component is adapted to configure the current to include an electroporation current.

67. The apparatus according to claim 62, wherein the control component is adapted to configure the current to include an iontophoretic current.

68. Apparatus for administration of a drug, comprising an ingestible capsule adapted to store the drug, the capsule comprising:

an environmentally-sensitive mechanism, adapted to change a state thereof responsively to a target location of the capsule within a gastrointestinal (GI) tract of a subject;

first and second electrodes; and

a control component, adapted to;

in response to a change of state of the environmentally-sensitive mechanism, facilitate passage of the drug through an epithelial layer of the GI tract by driving a current between the first and second electrodes, and

configure the current using parameters selected at least in part responsively to a property of the drug.

69. Apparatus for facilitating administration of a drug contained in a pill, the apparatus comprising an ingestible housing, which is not adapted to contain the drug or to be assembled in an integral unit with the drug, the housing comprising:

an ingestible environmentally-sensitive mechanism, adapted to change a state thereof responsive to a disposition thereof within a gastrointestinal (GI) tract of a subject; and

a drug-passage facilitation mechanism, which, in response to a change of state of the environmentally-sensitive mechanism, is adapted to facilitate the passage of the drug through an epithelial layer of the GI tract.

70. The apparatus according to claim 69,

wherein the environmentally-sensitive mechanism comprises a sensor adapted to sense an indication of a distance traveled by the housing in the GI tract, and

wherein the environmentally-sensitive mechanism is adapted to undergo the change of state responsive to the distance.

71. The apparatus according to claim 69, wherein the environmentally-sensitive mechanism comprises a camera, adapted to image the GI tract, and wherein the drug-passage facilitation mechanism is adapted to facilitate the passage of the drug in response to an image acquired by the camera.

72. The apparatus according to claim 69, wherein the disposition of the environmentally-sensitive mechanism includes a temperature in a vicinity of the environmentally-sensitive mechanism, wherein the environmentally-sensitive mechanism comprises a temperature sensor, and wherein the drug-passage facilitation mechanism is adapted to facilitate the passage of the drug in response to the temperature sensed by the temperature sensor.

73. The apparatus according to claim 69, wherein the disposition of the environmentally-sensitive mechanism includes a pH in a vicinity of the environmentally-sensitive mechanism, wherein the environmentally-sensitive mechanism comprises a pH sensor, and wherein the drug-passage facilitation mechanism is adapted to facilitate the passage of the drug in response to the pH sensed by the pH sensor.

74. The apparatus according to claim 69, wherein the environmentally-sensitive mechanism comprises a sensor, adapted to sense a characteristic of the GI tract, and wherein the environmentally-sensitive mechanism is adapted to facilitate the passage of the drug in response to the sensed characteristic.

75. The apparatus according to claim 69, wherein the environmentally-sensitive mechanism is adapted to undergo the change of state generally at an expected time of release of the drug from the drug pill.

76. The apparatus according to claim 69, wherein the environmentally-sensitive mechanism comprises a coating on a surface of the housing.

77. The apparatus according to claim 76, wherein the coating comprises a pH-sensitive coating.

78. Apparatus for facilitating administration of a drug contained in a pill, the apparatus comprising an ingestible housing, which is not adapted to contain the drug or to be assembled in an integral unit with the drug, the housing comprising:

at least two electrodes; and

a control component, adapted to facilitate the passage of the drug through an epithelial layer of a gastrointestinal (GI) tract of a subject by applying a current between the electrodes.

79. The apparatus according to claim 78, wherein the control component is adapted to configure the current to include a “

low intensity time-varying”

(LITV) signal.

80. The apparatus according to claim 78, wherein the control component is adapted to configure the current to include an electroporation current.

81. The apparatus according to claim 78, wherein the control component is adapted to configure the current to include an iontophoretic current.

82. Apparatus for use with a drug pill, the apparatus comprising:

a coupling mechanism, adapted to couple the drug pill to the apparatus;

an ingestible environmentally-sensitive mechanism, adapted to change a state thereof responsive to a disposition thereof within a gastrointestinal (GI) tract of a subject; and

a drug-passage facilitation mechanism, which, in response to a change of state of the environmentally-sensitive mechanism, is adapted to facilitate passage of a drug contained in the drug pill through an epithelial layer of the GI tract.

83. The apparatus according to claim 82, wherein the drug pill includes a commercially-available drug pill, and wherein the coupling mechanism is adapted to couple the commercially-available drug pill to the apparatus.

84. The apparatus according to claim 82, wherein the coupling mechanism comprises an adhesive.

85. Apparatus for use with a drug pill, the apparatus comprising:

a coupling mechanism, adapted to couple the drug pill to the apparatus;

at least two electrodes; and

a control component, adapted to facilitate passage of a drug contained in the drug pill through an epithelial layer of a gastrointestinal (GI) tract of a subject by applying a current between the electrodes.

86. The apparatus according to claim 85, wherein the control component is adapted to configure the current to include a “

low intensity time-varying”

(LITV) signal.

87. The apparatus according to claim 85, wherein the control component is adapted to configure the current to include an electroporation current.

88. The apparatus according to claim 85, wherein the control component is adapted to configure the current to include an iontophoretic current.

89. The apparatus according to claim 85, wherein the coupling mechanism comprises at least one of the electrodes.

90. The apparatus according to claim 89, wherein the at least one of the electrodes is configured to surround a portion of the drug pill once the drug pill has been coupled to the apparatus.

91. Apparatus for facilitating administration of a drug to a subject, the apparatus comprising:

a sensor unit, which comprises;

a sensor, adapted to detect an indication of a concentration of a substance in a blood circulation of the subject; and

a wireless transmitter, adapted to wirelessly transmit the indication; and

an ingestible capsule, which comprises;

a wireless receiver, adapted to receive the indication;

at least two electrodes; and

a control component, adapted to facilitate passage of the drug through an epithelial layer of a gastrointestinal (GI) tract of the subject by applying a current between the electrodes.

92. The apparatus according to claim 91, wherein the control component is adapted to configure the current to include a “

low intensity time-varying”

(LITV) signal.

93. The apparatus according to claim 91, wherein the control component is adapted to configure the current to include an electroporation current.

94. The apparatus according to claim 91, wherein the control component is adapted to configure the current to include an iontophoretic current.

95. The apparatus according to claim 91, wherein the substance includes the drug, and wherein the sensor is adapted to detect the indication of the concentration of the drug in the blood circulation.

96. The apparatus according to claim 91,

wherein the substance includes a calibrating substance,

wherein the sensor is adapted to detect the indication of the concentration of the calibrating substance in the blood circulation, and

wherein the control component is adapted to facilitate the passage of the calibrating substance and the drug through the epithelial layer of the GI tract, responsively to the received indication.

97. The apparatus according to claim 91, wherein the sensor comprises a noninvasive external sensor.

98. The apparatus according to claim 91, wherein the sensor comprises an invasive sensor.

99. The apparatus according to claim 91, wherein the ingestible capsule is adapted to store the drug.

100. The apparatus according to claim 91, wherein the ingestible capsule is not adapted to contain the drug or to be assembled in an integral unit with the drug.

101. The apparatus according to claim 91, wherein the drug is contained in a drug pill, and wherein the ingestible capsule comprises a coupling mechanism, adapted to couple the drug pill to the ingestible capsule.

102. The apparatus according to claim 91,

wherein the ingestible capsule comprises an environmentally-sensitive mechanism, adapted to change a state thereof responsively to a disposition of the capsule within the GI tract, and

wherein the control component is adapted to facilitate the passage of the drug through the epithelial layer in response to a change of state of the environmentally-sensitive mechanism.

103. The apparatus according to claim 91,

wherein the indication includes respective first and second indications, sensed at respective first and second times,

wherein the wireless transmitter is adapted to transmit the first indication subsequent to the first time, and to transmit the second indication subsequent to the second time, and

wherein the control component is adapted to apply first and second currents, responsive to the first and second indications.

104. The apparatus according to claim 103, wherein the sensor unit is adapted to.space the first and second times by at least 10 minutes.

105. The apparatus according to claim 103, wherein the control component is adapted to regulate a parameter of at least one of the currents, responsive to at least one of the indications.

106. The apparatus according to claim 91,

wherein the ingestible capsule comprises a capsule wireless transmitter,

wherein the sensor unit comprises a sensor unit wireless receiver, and

wherein the ingestible capsule is adapted to wirelessly notify the sensor unit of a property of the capsule, via the capsule wireless transmitter and the sensor unit wireless receiver.

107. The apparatus according to claim 106, wherein the property is selected from the list consisting of:

a location of the capsule, a status of the control component, a pH level of the GI tract, and a temperature of the GI tract, and wherein the capsule is adapted to wirelessly notify the sensor of the selected property.

108. The apparatus according to claim 91, wherein the substance includes a chemical, the blood concentration of which is affected by a blood concentration of the drug, and wherein the sensor is adapted to detect the indication of the concentration of the chemical in the blood circulation.

109. The apparatus according to claim 108, wherein the chemical is selected from the list consisting of:

glucose, growth hormone, and hemoglobin-bound oxygen, and wherein the sensor is adapted to detect the indication of the concentration of the selected chemical in the blood circulation.

110. Apparatus for facilitating administration of a drug to a subject, the apparatus comprising:

a sensor unit, which comprises;

a sensor, adapted to detect an indication of a physiological parameter of the subject; and

a wireless transmitter, adapted to wirelessly transmit the indication; and

an ingestible capsule, which comprises;

a wireless receiver, adapted to receive the indication;

at least two electrodes; and

a control component, adapted to facilitate passage of the drug through an epithelial layer of a gastrointestinal (GI) tract of the subject by applying an electrical current between the electrodes.

111. The apparatus according to claim 110, wherein the indication includes an indication of blood pressure of the subject, and wherein the sensor is adapted to sense the indication of blood pressure.

112. The apparatus according to claim 110, wherein the indication includes an indication of a heart-related parameter of the subject, and wherein the sensor is adapted to sense the indication of the heart-related parameter.

113. The apparatus according to claim 110, wherein the indication includes an indication of a level of activity of the subject, and wherein the sensor is adapted to sense the indication of the level of activity.

114. The apparatus according to claim 110, wherein the indication includes an indication of a temperature of the subject, and wherein the sensor is adapted to sense the indication of the temperature.

115. The apparatus according to claim 110, wherein the indication includes an indication of a circadian cycle of the subject, and wherein the sensor comprises clock circuitry adapted to sense the indication of the circadian cycle.

116. Apparatus for facilitating administration of a drug to a subject, the apparatus comprising:

first and second electrodes; and

a control component, adapted to facilitate passage of the drug through an epithelial layer of a gastrointestinal (GI) tract of the subject by driving the first and second electrodes to apply a “

low intensity time-varying”

(LITV) signal.

117. The apparatus according to claim 116, wherein the LITV signal includes a signal that creates a field that is less than about 5 Volts/cm and varies at a rate greater than about 1 Hz, and wherein the control component is adapted to drive the first and second electrodes to apply the signal that creates the field.

118. The apparatus according to claim 116, wherein the LITV signal includes a signal capable of opening tight junctions of the epithelial layer to an extent sufficient to allow at least a 100% increase in passage of the drug therethrough, and wherein the control component is adapted to drive the first and second electrodes to apply the signal capable of opening the tight junctions.

119. The apparatus according to claim 116, wherein the LITV signal includes a signal insufficient to cause electroporation of cells of the epithelial layer, and wherein the control component is adapted to drive the first and second electrodes to apply the signal that is insufficient to cause the electroporation.

120. A method for administration of a drug, comprising:

administering to a subject an ingestible capsule that includes the drug;

detecting a disposition of the capsule within a gastrointestinal (GI) tract of the subject; and

in response to detecting the disposition, facilitating, by the capsule, passage of the drug through an epithelial layer of the GI tract by applying a “

low intensity time-varying”

(LITV) signal.

121. The method according to claim 120, wherein the LITV signal includes a signal that creates a field that is less than about 5 Volts/cm and varies at a rate greater than about 1 Hz, and wherein applying the LITV signal comprises applying the signal that creates the field.

122. The method according to claim 120, wherein the LITV signal includes a signal capable of opening tight junctions of the epithelial layer to an extent sufficient to allow at least a 100% increase in passage of the drug therethrough, and wherein applying the LITV signal comprises applying the signal capable of opening the tight junctions.

123. The method according to claim 120, wherein the LITV signal includes a signal insufficient to cause electroporation of cells of the epithelial layer, and wherein applying the LITV signal comprises applying the signal that is insufficient to cause the electroporation.

124. The method according to claim 120,

wherein detecting the disposition of the capsule comprises sensing an indication of a distance traveled by the capsule in the GI tract, and

wherein facilitating the passage of the drug comprises facilitating the passage responsive to the distance.

125. The method according to claim 120, wherein detecting the disposition of the capsule comprises imaging the GI tract, and wherein applying the LITV signal comprises applying the LITV signal in response to an acquired image.

126. The method according to claim 120, wherein the disposition of the capsule includes a temperature in a vicinity of the capsule, wherein detecting the disposition of the capsule comprises sensing the temperature, and wherein applying the LITV signal comprises applying the LITV signal in response to the sensed temperature.

127. The method according to claim 120, wherein the disposition of the capsule includes a pH in a vicinity of the capsule, wherein detecting the disposition of the capsule comprises sensing the pH, and wherein applying the LITV signal comprises applying the LITV signal in response to the sensed pH.

128. The method according to claim 120, wherein detecting the disposition of the capsule comprises sensing a characteristic of the GI tract, and wherein applying the LITV signal comprises applying the LITV signal in response to the sensed characteristic.

129. The method according to claim 120, wherein facilitating the passage of the drug comprises applying the LITV signal, and applying an iontophoretic current.

130. The method according to claim 120, wherein applying the LITV signal comprises configuring the LITV signal using parameters selected at least in part responsively to the disposition of the capsule within the GI tract.

131. The method according to claim 120, wherein applying the LITV signal comprises configuring the LITV signal using parameters selected at least in part responsively to a property of the drug.

132. The method according to claim 120, wherein applying the LITV signal comprises applying the LITV signal at a current of less than about 5 mA.

133. The method according to claim 120, wherein applying the LITV signal comprises applying the LITV signal for a period of between about 1 and about 120 minutes.

134. The method according to claim 120, wherein applying the LITV signal comprises configuring the LITV signal to be sufficiently weak so as not to cause local activation of smooth muscle.

135. The method according to claim 120, wherein applying the LITV signal comprises configuring the LITV signal to include a series of pulses.

136. The method according to claim 135, wherein applying the LITV signal comprises applying the LITV signal at a current of less than about 5 mA.

137. The method according to claim 135, wherein applying the LITV signal comprises configuring the LITV signal to have a frequency of between about 1 and about 100 Hz.

138. The method according to claim 135, wherein applying the LITV signal comprises configuring the LITV signal to have a pulse duration of between about 0.1 and about 10 milliseconds.

139. The method according to claim 135, wherein applying the LITV signal comprises:

applying the LITV signal at a current of less than about 5 mA; and

configuring the LITV signal to have a frequency of between about 1 and about 100 Hz, and a pulse duration of between about 0.1 and about 10 milliseconds.

140. The method according to claim 135, wherein applying the LITV signal comprises applying the LITV signal at a voltage per centimeter of between about 0.5 and about 5 Volts/cm.

141. The method according to claim 120, wherein applying the LITV signal comprises applying the LITV signal in a train of bursts, each of the bursts including at least one pulse.

142. The method according to claim 141, wherein applying the LITV signal comprises configuring the train to have a repetition frequency of between about 6 and about 30 Hz.

143. The method according to claim 141, wherein applying the LITV signal comprises configuring each of the bursts to include between 1 and about 4 pulses.

144. The method according to claim 141, wherein applying the LITV signal comprises configuring each of the bursts to include a plurality of pulses, having a delay of about 4 to about 8 milliseconds between the start of each successive pulse.

145. The method according to claim 141, wherein applying the LITV signal comprises configuring each of the pulses to have a duration of between about 0.1 and about 2 milliseconds.

146. A method for administration of a drug, comprising:

administering to a subject an ingestible capsule that includes the drug;

detecting a disposition of the capsule within a gastrointestinal (GI) tract of the subject; and

in response to detecting the disposition, facilitating, by the capsule, passage of the drug through an epithelial layer of the GI tract by driving an electroporation current into the epithelial layer.

147. The method according to claim 146, wherein driving the electroporation current comprises configuring the electroporation current to have an AC voltage of between about 3 and about 50 Volts.

148. The method according to claim 146, wherein driving the electroporation current comprises configuring the electroporation current to have a frequency of between about 1 and about 300 Hz.

149. The method according to claim 146, wherein facilitating the passage of the drug comprises driving the electroporation current, and driving an iontophoretic current.

150. The method according to claim 146, wherein driving the electroporation current comprises configuring the electroporation current using parameters selected at least in part responsively to the disposition of the capsule within the GI tract.

151. The method according to claim 146, wherein driving the electroporation current comprises configuring the electroporation current using parameters selected at least in part responsively to a property of the drug.

152. A method for administration of a drug, comprising:

administering to a subject an ingestible capsule that includes the drug;

detecting a target location of the capsule within a gastrointestinal (GI) tract of the subject;

in response to detecting the target location, driving the drug directly through an epithelial layer of the GI tract by driving, by the capsule, a current into the epithelial layer; and

configuring the current using parameters selected at least in part responsively to the target location of the capsule within the GI tract.

153. The method according to claim 152, wherein configuring the current comprises configuring the current using parameters selected at least in part responsively to a property of the drug.

154. The method according to claim 152, wherein configuring the current comprises configuring the current to include a “

low intensity time-varying”

(LITV) signal.

155. The method according to claim 152, wherein configuring the current comprises configuring the current to include an electroporation current.

156. The method according to claim 152, wherein configuring the current comprises configuring the current to include an iontophoretic current.

157. A method for administration of a drug, comprising:

administering to a subject an ingestible capsule that includes the drug;

detecting a target location of the capsule within a gastrointestinal (GI) tract of the subject;

in response to detecting the target location, driving the drug directly through an epithelial layer of the GI tract by driving, by the capsule, a current into the epithelial layer; and

configuring the current using parameters selected at least in part responsively to a property of the drug.

158. The method according to claim 157, wherein configuring the current comprises configuring the current using parameters selected at least in part responsively to the target location of the capsule within the GI tract.

159. The method according to claim 157, wherein configuring the current comprises configuring the current to include a “

low intensity time-varying”

(LITV) signal.

160. The method according to claim 157, wherein configuring the current comprises configuring the current to include an electroporation current.

161. The method according to claim 157, wherein configuring the current comprises configuring the current to include an iontophoretic current.

162. A method for administration of a drug contained in a pill, comprising:

orally administering the pill to a subject;

orally administering to the subject an ingestible capsule that does not include the drug;

detecting a target location of the capsule within a gastrointestinal (GI) tract of the subject; and

in response to detecting the target location, facilitating, by the capsule, passage of the drug through an epithelial layer of the GI tract.

163. The method according to claim 162, wherein detecting the target location of the capsule comprises sensing an indication of a distance traveled by the housing in the GI tract.

164. The method according to claim 162, wherein detecting the target location of the capsule comprises imaging the GI tract, and detecting the target location responsive to an acquired image.

165. The method according to claim 162, wherein detecting the target location comprises sensing a characteristic of the GI tract.

166. A method for administration of a drug contained in a pill, comprising:

orally administering the pill to a subject;

orally administering to the subject an ingestible capsule that does not include the drug;

facilitating, by the capsule, passage of the drug through an epithelial layer of a gastrointestinal (GI) tract of the subject, by applying an electric current.

167. The method according to claim 166, wherein applying the current comprises configuring the current to include a “

low intensity time-varying”

(LITV) signal.

168. The method according to claim 166, wherein applying the current comprises configuring the current to include an electroporation current.

169. The method according to claim 166, wherein applying the current comprises configuring the current to include an iontophoretic current.

170. A method for administration of a drug, comprising:

coupling, to an ingestible capsule, a drug pill containing the drug;

administering the capsule to a subject;

detecting a target location of the capsule within a gastrointestinal (GI) tract of the subject; and

in response to detecting the target location, facilitating, by the capsule, passage of the drug through an epithelial layer of the GI tract.

171. The method according to claim 170, wherein the drug pill includes a commercially-available drug pill, and wherein coupling comprises coupling the commercially-available drug pill to the ingestible capsule.

172. The method according to claim 170, wherein coupling comprises coupling the drug pill to the ingestible capsule using an adhesive.

173. A method for administration of a drug, comprising:

coupling, to an ingestible capsule, a drug pill containing the drug;

administering the capsule to a subject;

facilitating, by the capsule, passage of the drug through an epithelial layer of a gastrointestinal (GI) tract of the subject, by applying an electric current.

174. The method according to claim 173, wherein applying the current comprises configuring the current to include a “

low intensity time-varying”

(LITV) signal.

175. The method according to claim 173, wherein applying the current comprises configuring the current to include an electroporation current.

176. The method according to claim 173, wherein applying the current comprises configuring the current to include an iontophoretic current.

177. The method according to claim 173, wherein applying the current comprises driving the current between at least two electrodes, and wherein coupling comprises coupling the drug pill to the ingestible capsule using at least one of the electrodes.

178. The method according to claim 177, wherein coupling using the at least one of the electrodes comprises positioning the at least one of the electrodes around a portion of the drug pill.

179. A method for facilitating administration of a drug to a subject, the method comprising:

administering an ingestible capsule to the subject;

detecting an indication of a concentration of a substance in a blood circulation of the subject;

wirelessly transmitting the indication;

receiving the indication at the ingestible capsule; and

responsively to the received indication, facilitating, by the capsule, passage of the drug through an epithelial layer of a gastrointestinal (GI) tract of the subject, by applying an electric current.

180. The method according to claim 179, wherein applying the current comprises configuring the current to include a “

low intensity time-varying”

(LITV) signal.

181. The method according to claim 179, wherein applying the current comprises configuring the current to include an electroporation current.

182. The method according to claim 179, wherein applying the current comprises configuring the current to include an iontophoretic current.

183. The method according to claim 179, wherein the substance includes the drug, and wherein detecting the indication of the concentration of the substance comprises detecting the indication of the concentration of the drug in the blood circulation.

184. The method according to claim 179,

wherein the substance includes a calibrating substance,

wherein detecting the indication of the concentration of the substance comprises detecting the indication of the concentration of the calibrating substance in the blood circulation, and

wherein facilitating the passage of the drug comprises facilitating passage of the calibrating substance and the drug through the epithelial layer of the GI tract, responsively to the received indication.

185. The method according to claim 179, wherein detecting the indication comprises noninvasively detecting the indication.

186. The method according to claim 179, wherein detecting the indication comprises invasively detecting the indication.

187. The method according to claim 179, wherein the ingestible capsule includes the drug, and wherein administering the ingestible capsule comprises administering the ingestible capsule that includes the drug.

188. The method according to claim 179, wherein administering the ingestible capsule comprises administering an ingestible capsule that does not contain the drug and that is not assembled in an integral unit with the drug.

189. The method according to claim 179, wherein the drug is contained in a drug pill, and wherein administering the ingestible capsule comprises coupling the drug pill to the ingestible capsule.

190. The method according to claim 179, comprising detecting a disposition of the ingestible capsule within the GI tract, and wherein facilitating the passage of the drug comprises facilitating the passage in response to detecting the disposition.

191. The method according to claim 179,

wherein the indication includes respective first and second indications,

wherein detecting the indication comprises detecting the first and second indications at respective first and second times,

wherein transmitting the indication comprises wirelessly transmitting the first indication subsequent to the first time, and wirelessly transmitting the second indication subsequent to the second time, and

wherein applying the current comprises applying first and second currents, responsive to the first and second indications.

192. The method according to claim 191, wherein applying the current comprises regulating at least one of the currents responsive to at least one of the indications.

193. The method according to claim 191, wherein detecting the first and second indications at the respective first and second times comprises spacing the first and second times by at least 10 minutes.

194. The method according to claim 179, comprising wirelessly transmitting, by the capsule, a property of the capsule.

195. The method according to claim 194, wherein the property is selected from the list consisting of:

a location of the capsule, a status of the capsule, a pH of the GI tract, and a temperature of the GI tract, and wherein wirelessly transmitting the property comprises wirelessly transmitting, by the capsule, the selected property.

196. The method according to claim 179, wherein the substance includes a chemical, the blood concentration of which is affected by a blood concentration of the drug, and wherein detecting the indication of the concentration of the substance comprises detecting an indication of the concentration of the chemical in the blood circulation.

197. The method according to claim 196, wherein the chemical is selected from the list consisting of:

glucose, growth hormone, and hemoglobin-bound oxygen, and wherein detecting the indication of the concentration of the chemical comprises detecting the indication of the concentration of the selected chemical in the blood circulation.

198. A method for facilitating administration of a drug to a subject, the method comprising:

administering an ingestible capsule to the subject;

detecting an indication of a physiological parameter of the subject;

wirelessly transmitting the indication;

receiving the indication at the ingestible capsule; and

responsively to the received indication, facilitating, by the capsule, passage of the drug through an epithelial layer of a gastrointestinal (GI) tract of the subject by applying an electrical current.

199. The method according to claim 198, wherein the indication includes an indication of blood pressure of the subject, and wherein detecting the indication comprises detecting the indication of blood pressure.

200. The method according to claim 198, wherein the indication includes an indication of a heart-related parameter of the subject, and wherein detecting the indication comprises detecting the indication of the heart-related parameter.

201. The method according to claim 198, wherein the indication includes an indication of a level of activity of the subject, and wherein detecting the indication comprises detecting the indication of the level of activity.

202. The method according to claim 198, wherein the indication includes an indication of a circadian cycle of the subject, and wherein detecting the indication comprises detecting the indication of the circadian cycle.

203. The method according to claim 202, wherein the drug includes an antithrombotic drug, and wherein facilitating the passage of the drug comprises facilitating the passage of the antithrombotic drug through the epithelial layer.

204. The method according to claim 198, wherein the indication includes an indication of a temperature of the subject, and wherein detecting the indication comprises detecting the indication of the temperature.

205. The method according to claim 204, wherein the drug includes an antibiotic, and wherein facilitating the passage of the drug comprises facilitating the passage of the antibiotic through the epithelial layer.

206. A method for administration of a drug, comprising:

administering the drug to a gastrointestinal (GI) tract of a subject; and

facilitating passage of the drug through an epithelial layer of the GI tract by applying a “

low intensity time-varying”

(LITV) signal.

207. The method according to claim 206, wherein the LITV signal includes a signal that creates a field that is less than about 5 Volts/cm and varies at a rate greater than about 1 Hz, and wherein applying the LITV signal comprises applying the signal that creates the field.

208. The method according to claim 206, wherein the LITV signal includes a signal capable of opening tight junctions of the epithelial layer to an extent sufficient to allow at least a 100% increase in passage of the drug therethrough, and wherein applying the LITV signal comprises applying the signal capable of opening the tight junctions.

209. The method according to claim 206, wherein the LITV signal includes a signal insufficient to cause electroporation of cells of the epithelial layer, and wherein applying the LITV signal comprises applying the signal that is insufficient to cause the electroporation.