Delivery of hydrophobic active agent particles
View Patent ↗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 polymeric layer, the polymeric layer comprising a hydrophilic outer surface, the polymeric layer comprising
a hydrophilic polymer having pendent photoreactive groups, the hydrophilic polymer comprising a photo-polyacrylamide; and
a photo-crosslinker comprising at least two aryl ketone functionalities;
an exposed therapeutic agent layer disposed outside of the polymeric layer, the exposed therapeutic agent layer contacting the hydrophilic outer surface, the exposed therapeutic agent layer comprising
a particulate hydrophobic therapeutic agent; and
a cationic agent selected from the group consisting of polyethyleneimine and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP);
wherein the exposed therapeutic agent layer is configured to directly contact an in vivo environment when the drug delivery coating is disposed within a tissue of a subject.
2. The drug delivery coating of claim 1 , 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.
3. The drug delivery coating of claim 1 wherein the photo-polyacrylamide is poly(N-3-aminopropyl)methacrylamide-co-N-(3-(4-benzoylbenzamido)propyl) methacrylamide.
4. The drug delivery coating of claim 1 wherein the photo-crosslinker is chosen from ethylenebis(4-benzoylbenzyldimethylammonium) dibromide and bis(4-benzoyl)phosphate sodium salt.
5. The drug delivery coating of claim 1 , 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.
6. The drug delivery coating of claim 1 , the particulate hydrophobic therapeutic agent and the cationic agent forming coated therapeutic agent particles.
7. The drug delivery coating of claim 1 , the hydrophobic therapeutic agent comprising rapamycin.
8. The drug delivery coating of claim 1 , the hydrophobic therapeutic agent comprising paclitaxel.
9. The drug delivery coating of claim 1 , the aryl ketone functionalities of the hydrophobic therapeutic agent comprising acetophenone, benzophenone, anthraquinone, anthrone, quinone, and anthrone-like heterocycles.
10. A drug delivery coating comprising
a polymeric layer, the polymeric layer comprising a hydrophilic outer surface;
a matrix layer disposed outside of the polymeric layer, the matrix layer contacting the hydrophilic outer surface, the matrix comprising
a particulate hydrophobic therapeutic agent; and
a cationic agent;
wherein the polymeric layer further comprises
a photo-polyacrylamide selected 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; and
a photo-crosslinker chosen from ethylenebis(4-benzoylbenzyldimethylammonium) dibromide and bis(4-benzoyl)phosphate sodium salt;
wherein the matrix layer directly contacts an in vivo environment when the drug delivery coating is disposed within a tissue of a subject and releases at least about 42.05 μg of the particulate hydrophobic therapeutic agent within 30 seconds of contacting a vessel wall.