Drug-containing particulate composition with cationic agent, associated medical devices, and methods for treatment
View Patent ↗The disclosure provides bioactive agent-containing particulates that include bioactive agent, biocompatible polymer, negatively charged groups, and a cationic agent. The particulates can be associated with a medical device, such as a balloon catheter, which can be used to move the particulates to a treatment site. Transfer of the particulates from the device to tissue is facilitated by the arrangement of the cationic and bioactive agent-containing particulates.
1. A bioactive agent delivery composition comprising
(a) a bioactive agent-containing particulate comprising:
a core particle comprising a bioactive agent and a first biocompatible polymer; and
a layer around the core particle comprising a second biocompatible polymer and that comprises negatively charged groups,
wherein the second biocompatible polymer is more water soluble than the first biocompatible polymer; and
(b) a cationic agent associated with the negatively charged groups of particulate, which provides the particulate with a positive zeta-potential.
2. The bioactive agent delivery composition of claim 1 wherein the first biocompatible polymer is a biodegradable polymer.
3. The bioactive agent delivery composition of claim 2 wherein the first biocompatible polymer is an aliphatic polyester co-alkylene oxide block copolymer.
4. The bioactive agent delivery composition of claim 1 wherein the first biocompatible polymer is present in the particulates in an amount in the range of 10% to 90% (wt).
5. The bioactive agent delivery composition of claim 1 wherein the bioactive agent is present in the particulate in an amount in the range of 10% to 90% (wt).
6. The bioactive agent delivery composition of claim 1 wherein the bioactive agent is a macrolide or a taxane.
7. The bioactive agent delivery composition of claim 1 wherein the particulate further comprises an alkyl-substituted chromanol.
8. The bioactive agent delivery composition of claim 1 wherein the particulate is spherical in shape.
9. The bioactive agent delivery composition of claim 1 wherein the second biocompatible polymer is formed from a composition comprising an acid group-containing monomer.
10. The bioactive agent delivery composition of claim 9 wherein the acid groups are partially neutralized.
11. The bioactive agent delivery composition of claim 1 wherein the second biocompatible polymer is present in the particulate in an amount less than a combined amount of the first biocompatible polymer and bioactive agent.
12. The bioactive agent delivery composition of claim 1 wherein the cationic agent is selected from the group consisting of cationic lipids, cationic polymers, and lipidoids.
13. The bioactive agent delivery composition of claim 1 , wherein the cationic agent is present in the composition in an amount in the range of 1% to 25% (wt).
14. The bioactive agent delivery composition of claim 1 wherein the particulates have a size of less than 25 μm.
15. A medical device having a surface associated with the bioactive agent delivery composition of claim 1 .
16. The medical device of claim 15 , wherein the balloon is an angioplasty balloon.
17. The medical device of claim 15 wherein the surface further comprises a hydrogel matrix and the composition is associated with the hydrogel matrix.
18. A method for treating a subject comprising placing a bioactive agent delivery composition of claim 1 in a subject, wherein the bioactive agent released from the particulates treats a condition in the subject.
19. A method for forming a bioactive agent delivery composition comprising a bioactive agent-containing particulate, comprising steps of:
forming a particle comprising a core particle comprising bioactive agent and a first biocompatible polymer, and a second biocompatible polymer comprising negatively charged groups, that is more water soluble first biocompatible polymer; and
contacting the particle with a composition comprising cationic agent.
20. The method of claim 19 wherein the step of adding, the second biocompatible polymer comprises an acid group-containing biocompatible polymer, and the acid groups are partially or completely neutralized.