Particle delivery techniques

Abstract

A method is provided for in vivo or ex vivo delivery of a preparation of powdered nucleic acid molecules into vertebrate tissue for transformation of cells in the tissue using needleless injection techniques. The method can be used to deliver therapeutically relevant nucleotide sequences to cells in mammalian tissue to provide gene therapy, elicit immunity or to provide antisense or ribozyme functions. A method for providing densified processed pharmaceutical compositions is also described. The method is used to convert non-dense pharmaceutical powders or particulate formulations into densified particles optimally suited for transdermal delivery using a needleless syringe. The method is also used to optimize the density and particle size of powders and particulate formulations for subsequent transdermal delivery thereof. Densified pharmaceutical compositions formed by the present methods are also provided.

1 . A method for delivering densified particles to a target tissue or cell, the method comprising the steps of: 
 (i) forming densified particles from a particulate pharmaceutical preparation, the method for forming the densified particles comprising compacting the preparation to provide a compacted pharmaceutical preparation and size-reducing the compacted preparation into densified particles of suitable size and density for transdermal delivery thereof by needleless injection; and    (ii) administering said densified particles to the target tissue or cell by needleless injection.    
   
   
       2 . The method of  claim 1 , wherein the particles have an average size predominantly in the range of about 10 to 250 μm.  
   
   
       3 . The method of  claim 1 , wherein the particles are delivered to a cell in epidermal tissue.  
   
   
       4 . The method of  claim 1 , wherein the particles are delivered to a cell in the stratum basal layer of skin tissue.  
   
   
       5 . The method of  claim 1 , wherein the particles are comprised of a nucleic acid molecule and a pharmaceutically acceptable excipient.  
   
   
       6 . The method of clam  1 , wherein the particles are delivered to the target tissue or cell in vivo or ex vivo.  
   
   
       7 . The method of  claim 1 , wherein the nucleic acid molecule comprises a nucleotide sequence encoding an immunogen.  
   
   
       8 . A method for forming densified particles from a particulate pharmaceutical preparation, comprising compacting the preparation to provide a compacted pharmaceutical preparation and size-reducing the compacted preparation into densified particles of suitable size and density for transdermal delivery thereof by needleless injection.  
   
   
       9 . A method according to  claim 8 , wherein the suitable size is in the range of about 0.1 to 150 μm mean diameter.  
   
   
       10 . A method according to  claim 8 , wherein the densified particles have a particle density in the range of about 0.5 to 3.0 g/cm 3 .  
   
   
       11 . A method according to  claim 8 , wherein size reducing of the compacted material is carried out by milling and/or sieving.  
   
   
       12 . A method according to  claim 8 , wherein the method further comprises selecting densified particles using size classification.  
   
   
       13 . A method according to  claim 8 , wherein the size classification of the densified particles is carried out using sieving or cyclone separation.  
   
   
       14 . A method according to  claim 8 , wherein the particulate pharmaceutical preparation is a preparation of a gene construct.  
   
   
       15 . A densified particulate pharmaceutical composition formed from a lyophilised or spray-dried pharmaceutical preparation, said densified composition having an average particle size in the range of about 0.1 to 250 μm mean diameter and a particle density in the range of 0.1 to 25 g/cm 3 .  
   
   
       16 . A composition according to  claim 15 , wherein the lyophilised or spray-dried pharmaceutical preparation is a heat-sensitive biopharmaceutical preparation.  
   
   
       17 . A composition according to  claim 15 , wherein the lyophilised or spray-dried pharmaceutical preparation is a preparation of a peptide or protein.  
   
   
       18 . A composition according to  claim 15 , wherein the particulate pharmaceutical preparation is a preparation of a gene construct.  
   
   
       19 . A composition according to  claim 15 , wherein the particle size is in the range of about 0.1 to 150 μm mean diameter.  
   
   
       20 . A composition according to  claim 15 , wherein the particle density is in the range of about 0.5 to 3.0 g/cm 3 .