Microporation of Tissue for Delivery of Bioactive Agents

Abstract

A method of enhancing the permeability of a biological membrane, including the skin or mucosa of an animal or the outer layer of a plant to a permeant is described utilizing microporation of selected depth and optionally one or more of sonic, electromagnetic, mechanical and thermal energy and a chemical enhancer. Microporation is accomplished to form a micropore of selected depth in the biological membrane and the porated site is contacted with the permeant. Additional permeation enhancement measures may be applied to the site to enhance both the flux rate of the permeant into the organism through the micropores as well as into targeted tissues within the organism.

1 - 73 . (canceled) 
   
   
       74 . An apparatus for delivering a formulation into an organism comprising:
 a supply of a dry powder formulation; and   a heat conducting element, which, when put in substantial physical contact with a selected area of a biological membrane of the organism, is capable of porating the biological membrane at the selected area to form at least one micropore 1-1000 μm in diameter, by delivering sufficient energy to the selected area such that the temperature of tissue-bound water and other vaporizable substances in the selected area is elevated above the vaporization point of the water and other vaporizable substances, thereby removing the biological membrane in the selected area, and wherein the apparatus enables the dry powder formulation, when the dry powder formulation is put in contact with the selected area, to be taken up through the micropore into the organism, wherein the apparatus delivers the dry powder formulation into the organism.   
   
   
       75 . The apparatus of  claim 74 , wherein the dry powder formulation comprises a peptide(s), protein(s), vaccine antigen, DNA or RNA. 
   
   
       76 . The apparatus of  claim 74 , wherein the dry powder formulation comprises adenovirus. 
   
   
       77 . The apparatus of  claim 74 , wherein the dry powder formulation comprises microparticles. 
   
   
       78 . The apparatus of  claim 77 , wherein said microparticles comprise a bioactive agent(s). 
   
   
       79 . The apparatus of  claim 78 , wherein said bioactive agent(s) is selected from the group consisting of peptide(s), protein(s), vaccine antigen(s), DNA or RNA. 
   
   
       80 . The apparatus of  claim 79 , wherein said DNA or RNA is naked, fragmented, encapsulated or coupled to another agent. 
   
   
       81 . An apparatus for delivering a bioactive agent into an organism comprising:
 a heat conducting element, which, when put in substantial physical contact with a selected area of a biological membrane of the organism, is capable of porating the biological membrane at the selected area to form at least one micropore 1-1000 μm in diameter, by delivering sufficient energy to the selected area such that the temperature of tissue-bound water and other vaporizable substances in the selected area is elevated above the vaporization point of the water and other vaporizable substances, thereby removing the biological membrane in the selected area, and wherein the apparatus enables the bioactive agent, when the bioactive agent is put in contact with the selected area, to be taken up through the micropore into the organism, wherein said bioactive agent is put in contact with the selected area in a form selected from the group consisting of a tablet and a bio-erodable matrix, wherein said bio-erodable matrix is fabricated in a manner to allow the bioactive agent to be released into the organism via the micropore, wherein the apparatus delivers the bioactive agent into the organism.   
   
   
       82 . A system for stimulating an immune response in an organism, comprising:
 a supply of a permeant; and   a heat conducting element, which, when put in substantial physical contact with a selected area of a biological membrane of the organism, is capable of porating the biological membrane at the selected area to form at least one micropore 1-1000 μm in diameter and at a depth coincident with increased concentration of langerhans cells, by delivering sufficient energy to the selected area such that the temperature of tissue-bound water and other vaporizable substances in the selected area is elevated above the vaporization point of the water and other vaporizable substances, thereby removing the biological membrane in the selected area, and wherein the system enables the permeant, when the permeant is put in contact with the selected area, to be taken up through the micropore into the organism, wherein the system stimulates the immune response in the organism.   
   
   
       83 . The system of  claim 82 , wherein the depth of the micropore is 180 microns to 250 microns. 
   
   
       84 . The system of  claim 82 , wherein the organism is an animal. 
   
   
       85 . The system of  claim 84 , wherein the animal is a human. 
   
   
       86 . The system of  claim 82 , wherein the permeant is a vaccine. 
   
   
       87 . The system of  claim 86 , wherein the vaccine comprises DNA or RNA. 
   
   
       88 . The system of  claim 82 , wherein the permeant is introduced into the epidermis via formed micropores at a depth coincident with increased concentration of langerhans cells. 
   
   
       89 . The system of  claim 82 , wherein the surface area of the selected area of the biological membrane is greater than the total area of the micropores. 
   
   
       90 . A system for delivering a formulation into an organism comprising:
 a supply of a dry powder formulation; and   a heat conducting element, which, when put in substantial physical contact with a selected area of a biological membrane of the organism, is capable of porating the biological membrane at the selected area to form at least one micropore 1-1000 μm in diameter, by delivering sufficient energy to the selected area such that the temperature of tissue-bound water and other vaporizable substances in the selected area is elevated above the vaporization point of the water and other vaporizable substances, thereby removing the biological membrane in the selected area, and wherein the system enables the dry powder formulation, when the dry powder formulation is put in contact with the selected area, to be taken up through the micropore into the organism, wherein the system delivers the dry powder formulation into the organism.   
   
   
       91 . The system of  claim 90 , wherein the dry powder formulation comprises a peptide(s), protein(s), vaccine antigen(s), DNA or RNA. 
   
   
       92 . The system of  claim 90 , wherein the dry powder formulation comprises microparticles. 
   
   
       93 . The system of  claim 92 , wherein said microparticles comprise a bioactive agent(s). 
   
   
       94 . The system of  claim 93 , wherein said bioactive agent(s) is selected from the group consisting of peptide(s), protein(s), vaccine antigen(s), DNA or RNA. 
   
   
       95 . The system of  claim 94 , wherein said DNA or RNA is naked, fragmented, encapsulated or coupled to another agent.