Delivery of hydrophobic active agent particles

Patent metadata

Field	Value
Publication number	US-10213528-B2
Application number	US-201615385112-A
Country	US
Kind code	B2
Filing date	Dec 20, 2016
Priority date	May 20, 2011
Publication date	Feb 26, 2019
Grant date	Feb 26, 2019

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 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.

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