Delivery of hydrophobic active agent particles
Embodiments of the invention include drug delivery coatings and devices including the same. In an embodiment, the invention includes a drug delivery coating including a polymeric layer. The polymeric layer can include a hydrophilic outer surface. The coating can also include a matrix contacting the hydrophilic outer surface. The matrix can include a particulate hydrophobic therapeutic agent and a cationic agent. The polymeric layer can further include a hydrophilic polymer having pendent photoreactive groups and a photo-crosslinker including two aryl ketone functionalities. Other embodiments are also included herein.
1. A drug delivery coating comprising
a base polymeric layer, the base polymeric layer comprising a hydrophilic surface;
a therapeutic agent layer contacting the hydrophilic surface of the base polymeric layer and having a composition different than the base polymeric layer, the therapeutic agent layer comprising
a particulate hydrophobic therapeutic agent; and
a cationic block copolymer comprising charged blocks and uncharged blocks disposed over the particulate hydrophobic therapeutic agent;
wherein the cationic block copolymer forms an exterior surface of the drug delivery coating; and
wherein a charge provided by the cationic block copolymer confers to the therapeutic agent layer an electrostatic attraction to negative charges or polar groups of a lipid bilayer of a cellular membrane and cellular components after implantation of a device bearing the coating in a subject.
2. The drug delivery coating of claim 1 , the cationic block copolymer comprising a PLGA block.
3. The drug delivery coating of claim 1 , the cationic block copolymer comprising a PEG block.
4. The drug delivery coating of claim 1 , the cationic block copolymer selected from the group consisting of PEG-PEI and PLGA-PEI.
5. The drug delivery coating of claim 1 , the base polymeric layer further comprising a photo-crosslinker comprising at least two aryl ketone functionalities.
6. The drug delivery coating of claim 5 , wherein the photo-crosslinker is selected from the group consisting of ethylenebis(4-benzoylbenzyldimethylammonium) dibromide and bis(4-benzoyl)phosphate sodium salt.
7. The drug delivery coating of claim 1 , wherein the base polymeric layer comprises a hydrophilic polymer having pendent photoreactive groups.
8. The drug delivery coating of claim 7 , the hydrophilic polymer having pendent photoreactive groups comprising a photo-polyacrylamide.
9. The drug delivery coating of claim 8 , wherein the photo-polyacrylamide is chosen from poly(N-3-aminopropyl)methacrylamide-co-N-(3-(4-benzoylbenzamido)propyl)methacrylamide; poly(acrylamide-co-N-(3-(4-benzoylbenzamido)propyl)methacrylamide), poly(acrylamide-co-maleic-6-aminocaproic acid-N-oxysuccinimide-co-N-(3-(4-benzoylbenzamido)propyl)methacrylamide) and poly(acrylamide-co-(3-(4-benzoylbenzamido)propyl)methacrylamide)-co-glycidylmethacrylate.
10. The drug delivery coating of claim 8 , wherein the photo-polyacrylamide is poly(N-3-aminopropyl)methacrylamide-co-N-(3-(4-benzoylbenzamido)propyl) methacrylamide.
11. The drug delivery coating of claim 8 , wherein the photo-polyacrylamide is poly(N-3-aminopropyl)methacrylamide-co-N-(3-(4-benzoylbenzamido)propyl)methacrylamide and the photo crosslinker is ethylenebis(4-benzoylbenzyldimethylammonium) dibromide.
12. The drug delivery coating of claim 1 , the particulate hydrophobic therapeutic agent and the cationic block polymer forming coated therapeutic agent particles.
13. A drug delivery device comprising
a substrate; and
a drug delivery coating disposed on the substrate, the drug delivery coating comprising
a base polymeric layer, the base polymeric layer comprising a hydrophilic surface;
a therapeutic agent layer contacting the hydrophilic surface of the base polymeric layer and having a composition different than the base polymeric layer, the therapeutic agent layer comprising
a particulate hydrophobic therapeutic agent; and
a cationic block copolymer comprising charged blocks and uncharged blocks disposed over the particulate hydrophobic therapeutic agent;
wherein the cationic block copolymer forms an exterior surface of the drug delivery coating; and
wherein a charge provided by the cationic block copolymer confers to the therapeutic agent layer an electrostatic attraction to negative charges or polar groups of a lipid bilayer of a cellular membrane and cellular components after implantation of the device within a vessel.
14. The drug delivery coating of claim 13 , the cationic block copolymer comprising a PLGA block.
15. The drug delivery coating of claim 13 , the cationic block copolymer comprising a PEG block.
16. The drug delivery coating of claim 13 , the cationic block copolymer selected from the group consisting of PEG-PEI and PLGA-PEI.