Delivery of hydrophobic active agent particles

Patent metadata

Field	Value
Publication number	US-9861727-B2
Application number	US-201514609270-A
Country	US
Kind code	B2
Filing date	Jan 29, 2015
Priority date	May 20, 2011
Publication date	Jan 9, 2018
Grant date	Jan 9, 2018

Abstract

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.

First claim

The invention claimed is:

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.

Assignees

• Surmodics Inc

Inventors

• Slager Joram
• Heyer Toni M
• Babcock David E

Classifications

• A61L2300/606

  Coatings · CPC title

• A61L2300/416

  Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus · CPC title

• A61L2300/258

  Genetic materials, DNA, RNA, genes, vectors, e.g. plasmids · CPC title

• A61L29/16

  Biologically active materials, e.g. therapeutic substances {(A61L29/048 takes precedence)} · CPC title

• A61L29/14

  Materials characterised by their function or physical properties {, e.g. lubricating compositions} · CPC title