Fluid-jet pens configured for making modulated release bioactive agents

Abstract

The present invention is drawn to methods of preparing a bioactive agent-containing emulsion for delivery to a biological system. This method can comprise the step of jetting a bioactive agent and a first fluid medium from a fluid-jet pen into a second fluid medium to form a bioactive agent-containing emulsion, wherein the second fluid comprises a continuous phase of the emulsion. Alternatively, a method of preparing a bioactive agent-containing liposome can comprise jetting a lipid-containing composition and a bioactive agent from a fluid-jet pen into a medium to form a bioactive agent-containing liposome carried by the medium.

What is claimed is:  
     
         1 . A method of preparing a bioactive agent-containing emulsion for delivery to a biological system, comprising jetting: 
 (a) a bioactive agent, and    (b) a first fluid medium, from a fluid-jet pen into a second fluid medium to form a bioactive agent-containing emulsion, wherein the second fluid comprises a continuous phase of the emulsion.    
     
     
         2 . A method as in  claim 1 , wherein the first fluid medium includes a surfactant.  
     
     
         3 . A method as in  claim 1 , wherein the first fluid medium is polar, and the second fluid medium is nonpolar.  
     
     
         4 . A method as in  claim 1 , wherein the first fluid medium is nonpolar, and the second fluid medium is polar.  
     
     
         5 . A method as in  claim 1 , wherein the first fluid is substantially hydrophobic, the second fluid is substantially hydrophilic, and the bioactive agent comprises a hydrophobic moiety.  
     
     
         6 . A method as in  claim 1 , wherein the first fluid is substantially hydrophilic, the second fluid is substantially hydrophobic, and the bioactive agent comprises a hydrophilic moiety.  
     
     
         7 . A method as in  claim 1 , wherein the emulsion is a microemulsion.  
     
     
         8 . A method as in  claim 7 , wherein the microemulsion comprises a surfactant present at from 0.1% to 10% by weight.  
     
     
         9 . A method as in  claim 8 , wherein the microemulsion comprises a surfactant present at from 0.1% to 1% by weight.  
     
     
         10 . A method as in  claim 1 , wherein the fluid-jet pen is a thermal fluid-jet pen.  
     
     
         11 . A method as in  claim 1 , wherein the fluid-jet pen is a piezo fluid-jet pen.  
     
     
         12 . A method as in  claim 1 , further comprising the step of positioning a jetting orifice of the fluid-jet pen within the second fluid during the jetting step.  
     
     
         13 . A method as in  claim 1 , wherein the bioactive agent and the first fluid medium are in the form of a mixture prior to jetting.  
     
     
         14 . A method as in  claim 1 , wherein the bioactive agent and the first fluid medium are admixed during the jetting step.  
     
     
         15 . A method as in  claim 1 , wherein the fluid-jet pen exerts shear force on the bioactive agent and the first fluid medium during jetting.  
     
     
         16 . A method as in  claim 1 , wherein the bioactive agent-containing emulsion is a microemulsion, and wherein the second fluid has a dropsize from 1 to 20 μm in diameter.  
     
     
         17 . A method as in  claim 16 , wherein the microemulsion is prepared without added surfactant.  
     
     
         18 . A method as in  claim 1 , wherein the emulsion is prepared at a physiological temperature.  
     
     
         19 . A method as in  claim 1 , wherein the emulsion formed is a bioactive agent-containing water-in-oil-in-water emulsion.  
     
     
         20 . A method as in  claim 1 , wherein the bioactive agent-containing emulsion is prepared on-site for delivery to a biological system.  
     
     
         21 . A method as in  claim 1 , further comprising the step of delivering the bioactive agent-containing emulsion to a biological system.  
     
     
         22 . A method as in  claim 1 , wherein the second fluid is within a second fluid-jet pen, said second fluid-jet pen being configured for firing the emulsion to a carrier medium.  
     
     
         23 . A method as in  claim 22 , wherein the carrier medium is liquid substrate.  
     
     
         24 . A method as in  claim 22 , wherein the carrier medium is a solid substrate.  
     
     
         25 . A method as in  claim 22 , wherein the carrier medium is a tissue or cellular site.  
     
     
         26 . A method of preparing a bioactive agent-containing liposome, comprising jetting: 
 (a) a lipid-containing composition, and    (b) a bioactive agent, from a fluid-jet pen into a carrier medium to form a bioactive agent-containing liposome carried by the carrier medium.    
     
     
         27 . A method as in  claim 26 , wherein the bioactive agent is substantially hydrophilic or amphiphilic.  
     
     
         28 . A method as in  claim 26 , wherein the bioactive agent is substantially hydrophobic.  
     
     
         29 . A method as in  claim 26 , wherein the fluid-jet pen is a thermal fluid-jet pen.  
     
     
         30 . A method as in  claim 26 , wherein the fluid-jet pen is a piezo fluid-jet pen.  
     
     
         31 . A method as in  claim 26 , wherein the lipid-containing composition is a phospholipid.  
     
     
         32 . A method as in  claim 26 , wherein the carrier medium is liquid substrate.  
     
     
         33 . A method as in  claim 26 , wherein the carrier medium is a solid substrate.  
     
     
         34 . A method as in  claim 26 , wherein the carrier medium is a tissue or cellular site.  
     
     
         35 . A method as in  claim 26 , wherein the bioactive agent-containing liposome is formed in the fluid-jet pen prior to jetting.  
     
     
         36 . A method as in  claim 26 , wherein the bioactive agent-containing liposome is formed during jetting.  
     
     
         37 . A method as in  claim 26 , further comprising the step of delivering the bioactive agent-containing liposome to a biological system.  
     
     
         38 . A method as in  claim 26 , wherein the bioactive agent-containing liposome is prepared on-site for delivery to a biological system.  
     
     
         39 . A bioactive agent release system, comprising a fluid-jet pen containing: 
 (a) a bioactive agent; and    (b) a release agent,    wherein the fluid-jet pen is configured for jetting the bioactive agent and the release agent, resulting in an association between the bioactive agent and the release agent.    
     
     
         40 . A system as in  claim 39 , wherein the association is an emulsion.  
     
     
         41 . A system as in  claim 39 , wherein the association is a microemulsion.  
     
     
         42 . A system as in  claim 39 , wherein the association is a liposome.  
     
     
         43 . A system as in  claim 39 , wherein the association is produced in the fluid-jet pen prior to jetting.  
     
     
         44 . A system as in  claim 39 , wherein the association is produced prior to loading into the fluid-jet pen.  
     
     
         45 . A system as in  claim 39 , wherein the association is produced during jetting.  
     
     
         46 . A system as in  claim 39 , wherein the bioactive agent and the release agent are in two separate phases within the fluid-jet pen.  
     
     
         47 . A system as in  claim 39 , wherein the bioactive agent and the release agent are mixed within the fluid-jet pen.  
     
     
         48 . A system as in  claim 39 , wherein the fluid-jet pen containing a bioactive agent; and a release agent are packaged in a sterile environment, thereby providing a sterile association upon jetting.  
     
     
         49 . A composition prepared in accordance with the method of  claim 1 .  
     
     
         50 . A composition prepared in accordance with the method of  claim 26.