Delivery of hydrophobic active agent particles
Inventors
Slager, Joram • Heyer, Toni M. • Babcock, David E.
Assignees
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Publication Number
US-11529440-B2
Publication Date
2022-12-20
Expiration Date
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.
Core Innovation
A drug delivery coating includes a base polymeric layer having a hydrophilic surface and a photo-crosslinker comprising at least two aryl ketone functionalities. A therapeutic agent layer forms an exterior surface and contacts the hydrophilic surface of the base polymeric layer while having a composition different than the base polymeric layer.
The therapeutic agent layer includes a particulate hydrophobic therapeutic agent and a cationic agent comprising polyethyleneimine (PEI). A ratio (wt./wt.) of particulate hydrophobic therapeutic agent to the cationic agent is about 99.9/0.1 to 90/10.
The base polymeric layer includes a hydrophilic polymer bearing pendent photoreactive groups, and the cationic agent is a PEI homopolymer or copolymer selected from PEG-PEI and PLGA-PEI. The base polymeric layer includes a photo-polyacrylamide composed of poly(N-3-aminopropyl)methacrylamide-co-N-(3-(4-benzoylbenzamido)propyl)methacrylamide and a photo crosslinker of ethylenebis(4-benzoylbenzyldimethylammonium) dibromide.
Claims Coverage
The independent claims cover 3 inventive features: a hydrophilic, photo-crosslinkable base polymeric layer; an exterior therapeutic agent layer containing a particulate hydrophobic therapeutic agent and a PEI-based cationic agent; and a wt./wt. ratio defining the particulate-to-PEI range. Dependent claims further refine the composition by narrowing the wt./wt. range and specifying PEI variant types and particular photo-crosslinker and hydrophilic polymer features.
Hydrophilic photo-crosslinked base polymeric layer with aryl ketone functionalities
A base polymeric layer comprising a hydrophilic surface and a photo-crosslinker comprising at least two aryl ketone functionalities.
Exterior therapeutic agent layer with particulate hydrophobic therapeutic agent and PEI
A therapeutic agent layer forming an exterior surface, the 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 agent comprising polyethyleneimine (PEI).
Defined wt./wt. ratio of particulate hydrophobic therapeutic agent to PEI
A ratio (wt./wt.) of particulate hydrophobic therapeutic agent to the cationic agent is about 99.9/0.1 to 90/10.
Narrowed wt./wt. ratio of particulate hydrophobic therapeutic agent to PEI
A ratio (wt./wt.) of particulate hydrophobic therapeutic agent to the cationic agent is about 99.9/0.1 to 95/5.
PEI homopolymer or copolymer as the cationic agent
The cationic agent is a polyethyleneimine (PEI) homopolymer or copolymer.
PEG-PEI or PLGA-PEI copolymer selection
The cationic agent comprises a copolymer selected from PEG-PEI and PLGA-PEI.
Hydrophilic polymer with pendent photoreactive groups in the base layer
The base polymeric layer includes a hydrophilic polymer bearing pendent photoreactive groups.
Specific photo-polyacrylamide and specific photo crosslinker for the base layer system
A photo-polyacrylamide composed of poly(N-3-aminopropyl)methacrylamide-co-N-(3-(4-benzoylbenzamido)propyl)methacrylamide and a photo crosslinker of ethylenebis(4-benzoylbenzyldimethylammonium) dibromide.
Across the independent and dependent claims, the core inventive structure is a hydrophilic base polymeric layer with a photo-crosslinker comprising at least two aryl ketone functionalities, together with an exterior therapeutic agent layer that includes a particulate hydrophobic therapeutic agent and a PEI-based cationic agent. Coverage is strengthened by defined wt./wt. ranges, selection of PEI homopolymer/copolymer and PEG-PEI/PLGA-PEI options, and further specification of hydrophilic photoreactive features and particular photo-polyacrylamide and photo crosslinker constituents.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Vascular and angioplasty stent-related devices.
Medical balloon catheter contexts.
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