Stable layer-by-layer coated particles
Systems and methods for coating a particle core with a layer-by-layer film are disclosed.
1. A particle, comprising:
a liposome core having a negatively charged outer surface and a diameter from about 100 nm to about 200 nm; and
a film coating the liposome core, the film comprising a first layer, a second layer, a third layer and a fourth layer, wherein:
the first layer, which coats the liposome core, includes poly-L-arginine (PLA);
the second layer, which coats the first layer, includes an siRNA therapeutic agent;
the third layer, which coats the second layer, includes PLA; and
the fourth layer, which coats the third layer, includes hyaluronic acid (HA),
and further wherein the liposome core comprises a second therapeutic agent.
2. The particle of claim 1 , wherein the second therapeutic agent is doxorubicin.
3. The particle of claim 1 , wherein the siRNA therapeutic agent is an siRNA targeting Multidrug Resistant Protein 1 (siRNA MRP1).
4. The particle of claim 1 , wherein the particles includes about 3500 copies of siRNA.
5. The particle of claim 1 , wherein the siRNA therapeutic agent is an siRNA targeting Multidrug Resistant Protein 1 (siRNA MRP1), the second therapeutic agent is doxorubicin, and the mass ratio of the siRNA therapeutic agent to doxorubicin is from about 1:1 to about 1.25:1.
6. A method of administering a combination of an siRNA therapeutic agent and a second therapeutic agent to a patient in need thereof, the method comprising:
administering to said patient a therapeutically effective amount of a pharmaceutical composition comprising the particles of claim 1 in a therapeutically acceptable carrier,
wherein the siRNA therapeutic agent and the second therapeutic agent are delivered to a tumor in a time-staggered manner.
7. The method of claim 6 , wherein the particles includes about 3500 copies of siRNA.
8. The method of claim 7 , wherein the siRNA therapeutic agent is an siRNA targeting Multidrug Resistant Protein 1 (siRNA MRP1), the second therapeutic agent is doxorubicin, and the mass ratio of the siRNA therapeutic agent to doxorubicin is from about 1:1 to about 1.25:1.