pH triggerable polymeric particles
A drug delivery system comprising pH triggerable particles is described. The pH triggerable particles comprise and agent(s) to be delivered, which is encapsulated in a matrix comprising a pH trigger agent and a polymer. Agents including nucleic acids may be delivered intracellularly using the inventive pH triggerable particles. Upon exposure to an acidic environment such as the endosome or phagosome of a cell, the particles dissolve or disrupt due to protonation or an increase in solubility of the pH triggering agent. Pharmaceutical compositions and methods of preparing and administering these particles are also described. These particles may be particularly useful in genetic vaccination.
1. A particle suitable for drug delivery to an animal comprising
at least one agent to be delivered;
a pH triggering agent wherein the pH triggering agent is a poly(beta-amino ester); and
a synthetic polymer;
wherein the particle releases the agent to be delivered at pH less than 7 by the dissolution or disruption of the particle, and;
wherein the agent, the pH triggering agent, and the synthetic polymer are distributed throughout the particle.
2. The particle of claim 1 wherein the particle is suitable for delivery to antigen presenting cells.
3. The particle of claim 1 wherein the particle is immunostimulatory.
4. The particle of claim 1 wherein the particle is suitable for intracellular delivery to antigen presenting cells.
5. The particle of claim 1 wherein the particle is suitable for delivery of an antigen for vaccination.
6. The particle of claim 1 wherein the particle is suitable for delivery of DNA vaccines.
7. The particle of claim 1 wherein the particle is suitable for delivery of enzymes.
8. The particle of claim 1 wherein the agent to be delivered is released at pH less than 6.
9. The particle of claim 1 wherein the agent to be delivered is released at pH less than 6.5.
10. The particle of claim 1 wherein the agent to be delivered is released at pH less than 5.
11. The particle of claim 1 , wherein the polymer is selected from the group consisting of polyesters, polyanhydrides, polyethers, polyamides, polyacrylates, polymethacrylates, polycarbamates, polycarbonates, polyureas, polyamines, poly(beta-amino esters), and polythioethers.
12. The particle of claim 1 , wherein the polymer does not include proteins, lipids, and polysaccharides.
13. The particle of claim 1 , wherein the particle does not include polyacrylates or polymethacrylates.
14. The particle of claim 1 , wherein the polymer is biodegradable and biocompatible.
15. The particle of claim 1 , wherein the largest diameter of the particle is less than 10 micrometers.
16. The particle of claim 1 , wherein the largest diameter of the particle ranges from 1 micrometer to 10 micrometers.
17. The particle of claim 1 , wherein the particle further comprises an adjuvant.
18. The particle of claim 1 , wherein the particle further comprises a targeting agent.
19. A pharmaceutical composition comprising the particles of claim 1 , and a pharmaceutically acceptable excipient.
20. The particle of claim, wherein the weight percent of the pH triggering agent is between 1% and 25%.
21. The particle of claim 1 , wherein the weight percent of the pH triggering agent is between 1% and 5%.
22. The particle of claim 1 , wherein the weight percent of the pH triggering agent is between 10% and approximately 30%.
23. The particle of claim 1 , wherein the weight percent of the pH triggering agent is between 15% and approximately 25%.
24. The particle of claim 1 , wherein the weight percent of the pH triggering agent is approximately 15%.