Fluid-jet pens configured for making modulated release bioactive agents
View Patent ↗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. The present invention is also drawn to fluid-jet pens and systems configured for making liposome- and emulsion-containing biological agents.
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 microemulsion, wherein the second fluid comprises a continuous phase of the microemulsion.
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 microemulsion comprises a surfactant present at from 0.1% to 10% by weight.
8. A method as in claim 7 , wherein the microemulsion comprises a surfactant present at from 0.1% to 1% by weight.
9. A method as in claim 1 , wherein the fluid jet pen is a thermal fluid jet pen.
10. A method as in claim 1 , wherein the fluid jet pen is a piezo fluid jet pen.
11. 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.
12. 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.
13. A method as in claim 1 , wherein the bioactive agent and the first fluid medium are admixed during the jetting step.
14. 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.
15. A method as in claim 1 , wherein the bioactive agent-containing microemulsion, and wherein the second fluid has a dropsize from 1 to 20 μm in diameter.
16. A method as in claim 15 , wherein the microemulsion is prepared without added surfactant.
17. A method as in claim 1 , wherein the microemulsion is prepared at a physiological temperature.
18. A method as in claim 1 , wherein the microemulsion formed is a bioactive agent-containing water-in-oil-in-water emulsion.
19. A method as in claim 1 , wherein the bioactive agent-containing microemulsion is prepared on-site for delivery to a biological system.
20. A method as in claim 1 , further comprising the step of delivering the bioactive agent-containing microemulsion to a biological system.
21. 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 microemulsion to a carrier medium.
22. A method as in claim 21 , wherein the carrier medium is liquid substrate.
23. A method as in claim 21 , wherein the carrier medium is a solid substrate.
24. A method as in claim 21 , wherein the carrier medium is a tissue or cellular site.