Method and apparatus for the delivery of plynucleotide vaccines to mammalia skin

Abstract

An object of the invention is to provide a method and apparatus for the delivery of polynucleotide vaccines into mammalian skin cells to increase T cell response and reduce pain and discomfort due to long electric waveform application and due to muscle contractions. The method includes administering a polynucleotide vaccine into the skin at an administration site, (b) applying a needle electrode to the skin in the vicinity to the administration site, and (c) applying a sequence of at least three single, operator-controlled, independently programmed, narrow interval electrical waveforms, which have pulse intervals that are less than 100 milliseconds, to deliver the 15 polynucleotide vaccine into the skin cells by electroporation.

1 . A method for the delivery of polynucleotide vaccines into mammalian skin cells, comprising the steps of:
 (a.) administering a polynucleotide vaccine into the skin at an administration site,   (b.) applying a needle electrode to the skin in the vicinity to the administration site,   (c.) applying a sequence of at least three single, operator-controlled, independently programmed, narrow interval electrical waveforms, which have pulse intervals that are less than 100 milliseconds, to deliver the polynucleotide vaccine into the skin cells by electroporation,   wherein the sequence of at least three waveforms has one, two, or three of the following characteristics: (1) at least two of the at least three waveforms differ from each other in waveform amplitude; (2) at least two of the at least three waveforms differ from each other in waveform width; and (3) a first waveform interval for a first set of two of the at least three waveforms is different from a second waveform interval for a second set of two of the at least three waveforms.   
     
     
         2 . The method of  claim 1  wherein step (a.) and step (b.) are carried out sequentially. 
     
     
         3 . The method of  claim 1  wherein step (a.) and step (b.) are carried out simultaneously using an electrode that is pre-coated with the polynucleotide vaccine. 
     
     
         4 . An apparatus for the delivery of polynucleotide vaccines into mammalian skin cells, comprising:
 a narrow interval electrical waveform generator, which is capable of applying a sequence of at least three single, operator-controlled, independently programmed, narrow interval electrical waveforms, which have pulse intervals that are less than 100 milliseconds, wherein the sequence of at least three, waveforms has one, two, or three of the following characteristics: (1) at least two of the at least three waveforms differ from each other in waveform amplitude; (2) at least two of the at least three waveforms differ from each other in waveform width; and (3) a first waveform interval for a first set of two of the at least three waveforms is different from a second waveform interval for a second set of two of the at least three waveforms, and   an electrode connected to said narrow interval electrical waveform generator, wherein said electrode is adapted to contact the skin into which a polynucleotide vaccine has been applied.   
     
     
         5 . The apparatus of  claim 4  wherein the polynucleotide vaccine has been applied to the skin prior to contacting the skin with the electrode. 
     
     
         6 . The apparatus of  claim 4  wherein the polynucleotide vaccine is pre-coated on the electrode and is applied to the skin at the same time the electrode is contacted with the skin. 
     
     
         7 . A method for the delivery of polynucleotide vaccines into mammalian skin cells, comprising the steps of:
 (a.) administering a polynucleotide vaccine into the skin at an administration site,   (b.) applying a needle electrode to the skin in the vicinity to the administration site,   (c.) applying a sequence of narrow interval electrical waveforms, which have pulse intervals that are less than 100 milliseconds, to deliver the polynucleotide vaccine into the skin cells by electroporation.   
     
     
         8 . An apparatus for the delivery of polynucleotide vaccines to mammalian skin cells, comprising:
 a narrow interval electrical waveform generator, which is capable of applying a sequence of narrow interval electrical waveforms, which have pulse intervals that are less than 100 milliseconds, and   an electrode connected to said narrow interval electrical waveform generator, wherein said electrode is adapted to contact the skin into which a polynucleotide vaccine has been applied.