Coating medical devices

• US 7,247,338 B2
• Filed: 11/21/2002
• Issued: 07/24/2007
• Est. Priority Date: 05/16/2001
• Status: Expired due to Term

• Current Assignee: Regents of The University of Minnesota (University of Minnesota)
• Original Assignee: Regents of The University of Minnesota (University of Minnesota)
• Inventors: Chen, Da-Ren, Pui, David Y. H.
• Primary Examiner(s): PARKER, FREDERICK JOHN
• Application Number:
  US10/301,473
• Publication Number:
  US 20030143315A1
• Time in Patent Office: 1,706 Days
• Field of Search: 427/2.14, 427/2.24, 427/2.28, 427/475, 427/476, 427/477, 427/483, 427/485, 427/486
• US Class Current: 427/2.24
• CPC Class Codes: A61F 2/86 Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
• CPC Class Codes: A61L 2300/00 Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
• CPC Class Codes: A61L 2300/622 Microcapsules
• CPC Class Codes: A61L 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: B05B 1/14 with multiple outlet openings B05B1/02, B05B1/26 take precedence; with strainers in or outside the outlet opening
• CPC Class Codes: B05B 13/0228 the movement of the objects being rotative B05B13/0242 takes precedence
• CPC Class Codes: B05B 5/025 Discharge apparatus, e.g. electrostatic spray guns
• CPC Class Codes: B05B 5/0255 spraying and depositing by electrostatic forces only
• CPC Class Codes: B05B 5/03 characterised by the use of gas , e.g. electrostatically assisted pneumatic spraying B05B5/04, B05B5/043, B05B5/047 take precedence
• CPC Class Codes: B05B 5/0533 Electrodes specially adapted therefor; Arrangements of electrodes
• CPC Class Codes: B05B 5/08 Plant for applying liquids or other fluent materials to objects
• CPC Class Codes: B05B 5/082 characterised by means for supporting, holding or conveying the objects
• CPC Class Codes: B05B 7/066 with an inner liquid outlet surrounded by at least one annular gas outlet
• CPC Class Codes: B05B 7/0884 the outlet orifices for jets constituted by a liquid or a mixture containing a liquid being aligned
• CPC Class Codes: B05D 1/002 the substrate being rotated
• CPC Class Codes: B05D 1/04 involving the use of an electrostatic field B05D1/025 and B05D1/14 take precedence
• CPC Class Codes: B05D 1/045 on non-conductive substrates

Abstract

Methods and systems for coating at least a portion of a medical device (e.g., a stent structure) include providing a plurality of coating particles (e.g., monodisperse coating particles) in a defined volume. For example, the particles may be provided using one or more nozzle structures, wherein each nozzle structure includes at least one opening terminating at a dispensing end. The plurality of coating particles may be provided in the defined volume by dispensing a plurality of microdroplets having an electrical charge associated therewith from the dispensing ends of the one or more nozzle structures through use of a nonuniform electrical field between the dispensing ends and the medical device. Electrical charge is concentrated on the particle as the microdroplet evaporates. With a plurality of coating particles provided in the defined volume, such particles can be moved towards at least one surface of the medical device to form a coating thereon (e.g., using an electric field and/or a thermophoretic effect).

Claims

1. A method of coating at least a portion of a medical device, the method comprising:

providing a medical device in a defined volume, wherein the medical device comprises at least one surface;

providing a plurality of monodisperse coating particles by electrospray in the defined volume, wherein the plurality of monodisperse coating particles have a nominal diameter of less than 10 micrometers and a geometrical standard deviation of less than 1.2, wherein providing the plurality of monodisperse coating particles comprises providing an electrical charge on the plurality of monodisperse coating particles, and further wherein providing the plurality of monodisperse coating particles comprises;

providing one or more nozzle structures, wherein each of the nozzle structures comprises at least a first and second opening terminating at the dispensing end of each nozzle structure from which a plurality of monodisperse coating particles having an electrical charge applied thereto is dispensed, and further wherein the method comprises providing a first flow of a first liquid composition at the first opening and providing a second flow of a second liquid composition at the second opening, and

dispensing the plurality of monodisperse coating particles from each nozzle structure by creating a nonuniform electrical field between the dispensing ends from which the plurality of monodisperse coating particles are dispensed and the medical device; and

moving a plurality of the coating particles towards the at least one surface of the medical device to form a coating thereon.

2. The method of claim 1, wherein moving the plurality of monodisperse coating particles towards the at least one surface of the medical device to form a coating thereon comprises moving the plurality of monodisperse coating particles towards the medical device using an electrical field.

3. The method of claim 1, wherein providing the plurality of monodisperse coating particles comprises dispensing a spray of microdroplets having an electrical charge associated therewith, wherein each of the microdroplets comprises a particle, wherein the electrical charge is concentrated on the particle as the microdroplet evaporates, and further wherein the electrical charge of the microdroplet concentrated on the particle is greater than about 30 percent of the Rayleigh charge limit for the microdroplet.

4. The method of claim 3, wherein the electrical charge of the microdroplet concentrated on the particle is greater than about 50 percent of the Rayleigh charge limit for the microdroplet.

5. The method of claim 1, wherein providing the plurality of monodisperse coating particles comprises dispensing a spray of microdroplets having an electrical charge associated therewith, wherein each of the microdroplets comprises a particle, wherein the electrical charge is concentrated on the particle as the microdroplet evaporates, and further wherein, prior to contact with the at least one surface of the medical device, a residual particle volume occupied by the evaporated microdroplet comprises less than about 20 percent of a solvent component of the microdroplet.

6. The method of claim 1, wherein the method further comprises creating an electrical field between an electrode and the medical device after the monodisperse coating particles are provided in the defined volume.

7. The method of claim 1, wherein moving the plurality of monodisperse coating particles towards the at least one surface of the medical device to form a coating thereon comprises moving the plurality of monodisperse coating particles towards the medical device using the nonuniform electrical field created between the dispensing ends from which the plurality of monodisperse coating particles are dispensed and the medical device.

8. The method of claim 7, wherein the medical device comprises a structure defining an interior volume, wherein the structure comprises at least an interior surface adjacent the interior volume and at least an exterior surface that is not adjacent to the interior volume, wherein providing the one or more nozzle structures comprises providing at least one nozzle structure having at least one opening at the dispensing end thereof located within the interior volume defined by the structure, and further wherein dispensing the plurality of monodisperse coating particles from the at least one nozzle structure comprises creating a nonuniform electrical field between the dispensing end of the at least one nozzle and the medical device.

9. The method of claim 8, wherein the at least one nozzle structure comprises a capillary tube comprised of a body portion and a tapered capillary tip at the dispensing end of the capillary tube.

10. The method of claim 1, wherein providing the one or more nozzle structures comprises providing a plurality of nozzle structures, wherein dispensing the plurality of monodisperse coating particles from the plurality of nozzle structures comprises creating a nonuniform electrical field between the dispensing ends thereof and the medical device.

11. The method of claim 1, wherein providing the medical device comprises providing a medical device in a fixed position within the defined volume.

12. The method of claim 1, wherein providing the medical device comprises providing a medical device that is movable within the defined volume.

13. The method of claim 1, wherein providing the medical device comprises providing a stent structure defined along a stent axis, wherein the stent structure comprises at least an interior surface adjacent a defined interior volume and at least an exterior surface that is not adjacent to the defined interior volume.

14. The method of claim 13, wherein providing the plurality of monodisperse coating particles comprises:

providing one or more nozzle structures, wherein each nozzle structure comprises at least one opening terminating at a dispensing end thereof from which a plurality of monodisperse coating particles having an electrical charge applied thereto is dispensed; and

dispensing the plurality of monodisperse coating particles from each nozzle structure by creating a nonuniform electrical field between the dispensing ends from which the plurality of monodisperse coating particles are dispensed and the stent structure device.

15. The method of claim 14, wherein method further comprises adjusting the strength of the nonuniform electrical field to prevent particles from reaching the interior surface of the stent structure.

16. The method of claim 15, wherein providing the one or more nozzle structures comprises providing at least one nozzle structure having at least one opening at the dispensing end thereof located within the interior volume defined by the stent structure, and further wherein dispensing the plurality of monodisperse coating particles from the at least one nozzle structure comprises creating a nonuniform electrical field between the dispensing end thereof and the stent structure.

17. The method of claim 1, wherein moving the plurality of monodisperse coating particles towards the at least one surface of the medical device comprises using a thermophoretic effect to move the plurality of monodisperse coating particles towards the at least one surface of the medical device.

18. The method of claim 17, wherein providing the medical device comprises providing a stent structure defined along a stent axis, wherein the stent structure comprises at least an interior surface adjacent an interior volume and an exterior surface, wherein the method farther comprises positioning the stent structure such that the stent axis coincides with an axis of an elongated element located within the interior volume of the stent structure, and further wherein moving a plurality of coating particles towards the at least one surface of the stent structure to form a coating thereon comprises holding the elongated element at a lower temperature than the temperature in the defined volume adjacent the exterior surface of the stent structure such that thermophoretic effect moves the coating particles towards the at least one surface of the stent structure.

19. The method of claim 1, wherein providing the medical device comprises providing a cylindrical stent structure defined along a stent axis, wherein the stent structure comprises at least an interior surface adjacent an interior volume and at least an exterior surface that is not adjacent to the interior volume, wherein moving a plurality of monodisperse coating particles towards the at least one surface of the stent structure to form a coating thereon comprises at least rotating the stent structure about the stent axis.

20. The method of claim 1, wherein moving a plurality of monodisperse coating particles towards the at least one surface of the medical device to form a coating thereon comprises moving the stent structure linearly along the stent axis.

21. The method of claim 1, wherein the method further comprises controlling the amount of monodisperse coating particles provided into the defined volume.

22. The method of claim 1, wherein the plurality of coating particles have a nominal diameter of greater than about 1 nanometer and less than about 100 nanometers.

23. The method of claim 1, wherein the plurality of coating particles comprise at least one biologically active ingredient or a coated biologically active ingredient.

24. The method of claim 23, wherein the plurality of coating particles comprise at least one of DNA or coated DNA.

25. The method of claim 1, wherein the at least one surface of the medical device comprises a conductive surface.

26. The method of claim 1, wherein the at least one surface of the medical device is a non-conductive surface.

27. The method of claim 1, wherein the first opening is concentric with the second opening.

28. The method of claim 1, wherein the at least one surface of the medical device comprises a polymer.

29. The method of claim 1, wherein the method further comprises charging at least a portion of one or more surfaces of the medical device.

30. The method of claim 1, wherein the method further comprises positioning masking material proximate the medical device to prevent coating one or more portion thereof.

31. The method of claim 1, wherein providing a first flow of a first liquid composition at the first opening comprises providing a first flow comprising at least one of a solvent, a polymer, and one or more biologically active ingredients;

and wherein providing a second flow of a second liquid composition at the second opening comprises providing a second flow comprising at least one of a solvent, a polymer, and one or more biologically active ingredients.

32. The method of claim 1,wherein providing a second flow of a second liquid composition at the second opening comprises controlling conductivity of the plurality of monodisperse coating particles using the second flow.

33. The method of claim 1, wherein providing the plurality of monodisperse particles comprises providing a plurality of coated particles.

34. The method of claim 1, wherein the first flow and the second flow comprise liquid compositions that have different surface tension and/or different conductivity.

35. The method of claim 1, wherein providing one or more nozzle structures comprises defining a first opening of at least one nozzle structure using a first defining structure and a second opening of the at least one nozzle structure using a second defining structure, wherein at least one of the first defining structure and second defining structure is conductive.

36. A method of coating at least a portion of a medical device, the method comprising:

providing a medical device in a defined volume, wherein the medical device comprises at least one surface;

providing one or more nozzle structures, wherein each nozzle structure comprises at least a first and second opening terminating at the dispensing end of each nozzle structure, and wherein the method further comprises;

providing a first flow of a first liquid composition at the first opening, and

providing a second flow of a second liquid composition at the second opening;

providing a plurality of coating particles in the defined volume, wherein providing the plurality of coating particles comprises dispensing a plurality of microdroplets having an electrical charge associated therewith from the dispensing ends of the one or more nozzle structures by creating a nonuniform electrical field between the dispensing ends and the medical device, wherein each of the microdroplets comprises at least a particle, and further wherein the electrical charge is concentrated on the particle as the microdroplet evaporates; and

moving the plurality of coating particles towards the medical device to form a coating on the at least one surface of the medical device using the nonuniform electrical field created between the dispensing ends from which the plurality of coating particles is established and the medical device.

37. The method of claim 36, wherein the plurality of coating particles in the defined volume have a nominal diameter of less than 10 micrometers and a geometrical standard deviation of less than 1.2.

38. The method of claim 36, wherein providing the plurality of microdroplets comprises providing a plurality of microdroplets having electrical charge associated therewith that is greater than about 30 percent of the Rayleigh charge limit for the microdroplet.

39. The method of claim 36, wherein prior to contact with the at least one surface of the medical device, a residual particle volume occupied by the evaporated microdroplet comprises less than about 20 percent of a solvent component of the microdroplet.

40. The method of claim 36, wherein providing the medical device comprises providing a stent structure defined along a stent axis, wherein the stent structure comprises at least an interior surface adjacent a defined interior volume and at least an exterior surface.

41. The method of claim 40, wherein the method further comprises adjusting the strength of the nonuniform electrical field to prevent particles from reaching the interior surface of the stent structure.

42. The method of claim 40, wherein providing the one or more nozzle structures comprises providing at least one nozzle structure having at least one opening at the dispensing end thereof located within the defined interior volume of the stent structure, and further wherein dispensing the plurality of monodisperse coating particles from the at least one nozzle structure comprises creating a nonuniform electrical field between the dispensing end thereof and the stent structure.

43. The method of claim 42, wherein the at least one nozzle structure comprises a capillary tube comprised of a body portion and a tapered capillary tip at the dispensing end of the capillary tube.

44. The method of claim 40, wherein moving the plurality of coating particles towards the at least one surface of the stent structure to form a coating thereon comprises at least rotating the stent structure about the stent axis relative to the one or more nozzle structures.

45. The method of claim 40, wherein moving the plurality of coating particles towards the at least one surface of the medical device to form a coating thereon comprises moving the stent structure linearly along the stent axis relative to the one or more nozzle structures.

46. The method of claim 40, wherein the method further comprises controlling the amount of coating particles provided into the defined volume.

47. The method of claim 40, wherein the plurality of coating particles have a nominal diameter of greater than about 1 nanometer and less than about 500 nanometers.

48. The method of claim 40, wherein the plurality of coating particles comprises at least one biologically active ingredient or at least one coated biologically active ingredient.

49. The method of claim 40, wherein providing the stent structure comprises providing a medical device in a fixed position within the defined volume during coating of the tent structure.

50. The method of claim 40, wherein the method further comprises:

providing an elongated cylindrical body member defining an interior volume thereof along an axis;

positioning the stent structure along the axis of the elongated cylindrical body member; and

positioning a plurality of nozzle structures radially about the axis of the elongated cylindrical body member and linearly along the elongated cylindrical body member in the direction of the axis thereof.

51. The method of claim 50, wherein each of a plurality of the nozzle structures comprises a capillary tube comprised of a body portion and a tapered capillary tip at the dispensing end of the capillary tube.

52. The method of claim 50, wherein each of a plurality of the nozzle structures comprises a tapered portion used to define an opening, and further wherein at least a part of each of the plurality of the nozzle structures extend from an integral conductive portion associated with the body member.

53. The method of claim 50, wherein each of a plurality of the nozzle structures comprises a solid post along a center axis extending through an opening at the dispensing end.

54. The method of claim 50, wherein each of a plurality of the nozzle structures comprises an elongated radial opening in the body member.

55. The method of claim 50, wherein each of a plurality of the nozzle structures comprises an elongated opening in the body member lying parallel to the axis thereof.

56. The method of claim 40, wherein the method further comprises:

positioning the stent structure such that the stent axis coincides with an axis of an elongated element; and

using spacing elements to maintain a distance between the stent structure and the elongated element.

57. The method of claim 40, wherein the method further comprises:

positioning the stent structure such that the stent axis coincides with an axis of an elongated element, wherein the elongated element is sized based on the defined interior volume of the stent structure such that a surface of the elongated element is in direct contact with the interior surface of the stent structure; and

removing the elongated element from the interior volume of the stent structure after a plurality of coating particles are moved towards the exterior surface of the stent structure to form a coating thereon.

58. The method of claim 57, wherein the stent structure comprises open framework comprising stent material lying radially from the stent axis and a configuration of openings separating portions of the stent material, wherein the elongated element is sized to stretch the stent structure from a normal state.

59. The method of claim 57, wherein the stent structure comprises open framework comprising stent material lying radially from the stent axis and a configuration of openings separating portions of the stent material, and further wherein the elongated element is removed from the interior volume of the stent structure after a plurality of coating particles are moved towards the exterior surface of the stent structure resulting in a sheath over the open framework including the openings separating portions of the stent material.

60. The method of claim 40, wherein the stent structure comprises open framework comprising stent material lying radially from the stent axis and a configuration of openings separating portions of the stent material, wherein the method further comprises:

providing a conductive elongated element along the axis of the stent structure, wherein the stent structure and the conductive elongated element are spaced a distance apart; and

creating an electric field between the conductive elongated element and the stent structure that is opposite the nonuniform electric field created between the dispensing ends of the nozzle structures and the stent structure.

61. The method of claim 40, wherein the stent structure comprises open framework comprising stent material lying radially from the stent axis and a configuration of openings separating portions of the stent material, wherein the method further comprises:

providing an elongated element along the axis of the stent structure, wherein the stent structure and the conductive elongated element are spaced a distance apart; and

using the elongated element to provide a gas stream within the defined interior volume of the stent structure.

62. The method of claim 36, wherein providing the medical device comprises providing a cylindrical stent structure defined along a stent axis, wherein the stent structure comprises at least an interior surface adjacent an interior volume and at least an exterior surface that is not adjacent to the interior volume, wherein moving a plurality of coating particles towards the at least one surface of the medical device to form a coating thereon is performed with the stent structure in a vertical position such that the stent does not sag along its stent axis.

63. The method of claim 36, wherein the at least one surface of the medical device comprises a conductive surface.

64. The method of claim 36, wherein the at least one surface of the medical device is a non-conductive surface.

65. The method of claim 36, wherein the first opening is concentric with the second opening.

66. The method of claim 36, wherein the at least one surface of the medical device comprises a polymer.

67. The method of claim 36, wherein the method further comprises charging at least a portion of one or more surfaces of the medical device.

68. The method of claim 36, wherein the method further comprises positioning masking material proximate the medical device to prevent coating one or more portions thereof.

69. The method of claim 36, wherein providing a first flow of a first liquid composition at the first opening comprises providing a first flow comprising at least one of a solvent, a polymer, and one or more biologically active ingredients;

and wherein providing a second flow of a second liquid composition at the second opening comprises providing a second flow comprising at least one of a solvent, a polymer, and one or more biologically active ingredients.

70. The method of claim 36, wherein providing a second flow of a second liquid composition at the second opening comprises controlling conductivity of the plurality of coating particles using the second flow.

71. The method of claim 36, wherein providing the plurality of particles comprises providing a plurality of coated particles.

72. The method of claim 36, wherein the first flow and the second flow comprise liquid compositions that have different surface tension and/or different conductivity.

73. The method of claim 36, wherein providing one or more nozzle structures comprises defining a first opening of at least one nozzle structure using a first defining structure and a second opening of the at least one nozzle structure using a second defining structure, wherein at least one of the first defining structure and second defining structure is conductive.

74. A method of coating a stent structure, the method comprising:

providing a stent structure in a defined volume along a stent axis, wherein the stent structure comprises at least an interior surface adjacent a defined interior volume and at least an exterior surface;

coating at least a portion of the interior surface of the stent structure adjacent the defined interior volume using at least a plurality of first coating particles, wherein coating at least a portion of the interior surface of the stent structure adjacent the defined interior volume using at least a plurality of first coating particles comprises;

providing one or more nozzle structures, wherein each nozzle structure comprises at least one opening terminating at a dispensing end, wherein at least one nozzle structure has at least one opening at the dispensing end thereof located within the defined interior volume of the stent structure;

providing a plurality of first coating particles in the interior defined volume, wherein providing the plurality of first coating particles comprises dispensing a plurality of microdroplets having an electrical charge associated therewith from the dispensing end of the at least one nozzle structure by creating a nonuniform electrical field between the dispensing end and the stent structure, wherein each of the microdroplets comprises at least a particle, and further wherein the electrical charge is concentrated on the particle as the microdroplet evaporates; and

moving the plurality of first coating particles towards the interior surface to form a coating thereon using the nonuniform electrical field created between the dispensing end and the stent structure; and

coating at least a portion of the exterior surface of the stent structure using at least a plurality of second coating particles, wherein the plurality of first coating particles is different than the plurality of second coating particles.

75. The method of claim 74, wherein the at least one nozzle structure comprises a capillary tube comprised of a body portion and a tapered capillary tip at the dispensing end of the capillary tube.

76. The method of claim 74, wherein each of the nozzle structures comprises at least a first and second opening terminating at the dispensing end of each nozzle structure.

77. The method of claim 76, wherein the method further comprises:

providing a first flow of a first fluid composition at the first opening; and

providing a second flow of a second fluid composition at the second opening.

78. The method of claim 76, wherein the first opening is concentric with the second opening.

80. The method of claim 74, wherein the particles of at least one of the plurality of first coating particles and the plurality of second coating particles have a nominal diameter of less than 10 micrometers and a geometrical standard deviation of less than 1.2.

81. The method of claim 74, wherein the method further comprises controlling an amount of at least one of the plurality of first coating particles and the plurality of second coating particles provided into the interior volume or the defined volume.

82. The method of claim 74, wherein the plurality of first coating particles comprise anti-coagulant particles.

83. The method of claim 74, wherein the plurality of second coating particles comprise anti-inflammatory particles.

79. A method of coating a stent structure, the method comprising:

providing a stent structure in a defined volume along a stent axis, wherein the stent structure comprises at least an interior surface adjacent a defined interior volume and at least an exterior surface;

coating at least a portion of the interior surface of the stent structure adjacent the defined interior volume using at least a plurality of first coating particles; and

coating at least a portion of the exterior surface of the stent structure using at least a plurality of second coating particles, wherein the plurality of first coating particles is different than the plurality of second coating particles, wherein coating at least a portion of the exterior surface of the stent structure using at least a plurality of second coating particles comprises;

providing one or more nozzle structures, wherein each nozzle structure comprises at least a first and second opening terminating at the dispensing end of each nozzle structure, and wherein the method further comprises;

providing a first flow of a first liquid composition at the first opening, and

providing a second flow of a second liquid composition at the second opening;

providing a plurality of second coating particles in the defined volume, wherein providing the plurality of second coating particles comprises dispensing a plurality of microdroplets having an electrical charge associated therewith from the dispensing ends of the one or more nozzle structures by creating a nonuniform electrical field between the dispensing ends and the stent structure, wherein each of the microdroplets comprises at least a particle, and further wherein the electrical charge is concentrated on the particle as the microdroplet evaporates; and

moving the plurality of second coating particles towards the medical device to form a coating on the at least one surface of the medical device using the nonuniform electrical field created between the dispensing ends from which the plurality of coating particles is established and the medical device.

84. The method of claim 79, wherein the particles of at least one of the plurality of first coating particles and the plurality of second coating particles have a nominal diameter of less than 10 micrometers and a geometrical standard deviation of less than 1.2.

85. The method of claim 79, wherein the method further comprises controlling an amount of at least one of the plurality of first coating particles and the plurality of second coating particles provided into the interior volume or the defined volume.

86. The method of claim 79, wherein the plurality of first coating particles comprise anti-coagulant particles.

87. The method of claim 79, wherein the plurality of second coating particles comprise anti-inflammatory particles.

88. The method of claim 79, wherein the at least one surface of the medical device comprises a conductive surface.

89. The method of claim 79, wherein the at least one surface of the medical device is a non-conductive surface.

90. The method of claim 79, wherein the first opening is concentric with the second opening.

91. The method of claim 79, wherein the at least one surface of the medical device comprises a polymer.

92. The method of claim 79, wherein the method further comprises charging at least a portion of one or more surfaces of the medical device.

93. The method of claim 79, wherein the method further comprises positioning masking material proximate the medical device to prevent coating one or more portions thereof

94. The method of claim 79, wherein providing a first flow of a first liquid composition at the first opening comprises providing a first flow comprising at least one of a solvent, a polymer, and one or more biologically active ingredients;

and wherein providing a second flow of a second liquid composition at the second opening comprises providing a second flow comprising at least one of a solvent, a polymer, and one or more biologically active ingredients.

95. The method of claim 79, wherein providing a second flow of a second liquid composition at the second opening comprises controlling conductivity of the plurality of coating particles using the second flow.

96. The method of claim 79, wherein at least one of the plurality of first coating particles and the plurality of second coating particles comprises a plurality of coated particles.

97. The method of claim 79, wherein the first flow and the second flow comprise liquid compositions that have different surface tension and/or different conductivity.