PEM layer-by-layer systems for coating substrates to improve bioactivity and biomolecule delivery

Patent metadata

Field	Value
Publication number	US-11149166-B2
Application number	US-201414778331-A
Country	US
Kind code	B2
Filing date	Apr 3, 2014
Priority date	Apr 3, 2013
Publication date	Oct 19, 2021
Grant date	Oct 19, 2021

Abstract

The invention relates to polyelectrolyte multilayer coatings and, methods for their preparation and application to substrates to enhance the bioactivity and corrosion protection of the substrates' surface. The invention is particularly suitable for coating substrates employed for medical applications, such as but not limited to medical implant devices for drug and/or biologics delivery in a patient. The substrate has a positive or negative charge. The polyelectrolyte multilayer coatings include at least a first polymer layer and a second polymer layer. The first polymer and second polymer have opposite charges. Each of the polymer layers is individually applied using a layer-by-layer such that an alternating charge multilayer coating is formed.

First claim

The invention claimed is:

1. A coated medical implant device, comprising:
a biodegradable magnesium-based substrate;
a pretreatment agent selected from the group consisting of alkali metal hydroxide, hydrogen fluoride and combinations thereof, applied to a surface of the biodegradable magnesium-based substrate to form a charged substrate having a positive charge or a negative charge;
a polyelectrolyte multilayer coating deposited on the charged substrate, comprising:
a plurality of interfacing, individual polymer layers, comprising:
one or more synthetic polymer layers comprising poly-L-lysine having a positive charge; and
one or more natural polymer layers comprising alginate having a negative charge,

wherein an initial layer of the plurality of interfacing, individual polymer layers deposited on the charged substrate and the charged substrate have opposite charges, and
wherein the plurality of interfacing, individual polymer layers has alternating layers of the one or more synthetic polymer layers and the one or more natural polymer layers; and
an outer polymer layer comprising one of the one or more natural polymer layers comprising alginate;

a chemical cross-linking agent comprising a solution of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride with N-hydroxysulfosuccinimide sodium salt, deposited on the outer polymer layer to immobilize fibronectin and form a modified outer surface;
fibronectin immobilized on the modified outer surface; and
an active substance, in addition to the fibronectin, deposited on the modified outer surface.

2. The device of claim 1 , wherein the alkali metal hydroxide comprises sodium hydroxide.

3. The device of claim 1 , wherein the poly-L-lysine and the alginate are each in the form of a solution and the one or more synthetic and natural polymer layers are formed by dipping the charged substrate into the solutions.

4. The device of claim 1 , wherein the active substance is selected from the group consisting of drugs, biologic materials, growth factors, DNA, transfecting agents, living molecules and combinations thereof.

5. The device of claim 1 , wherein the active substance is deposited on one or more of the plurality of interfacing, individual polymer layers in addition to being deposited on the modified outer surface.

Assignees

• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education

Inventors

• Kumta Prashant N
• Kunjukunju Sangeetha
• Ostrowski Nicole J
• Roy Abhijit
• Lee Boeun
• Ramanathan Madhumati

Classifications

• A61L27/04 Primary

  Metals or alloys · CPC title

• A61L27/58

  Materials at least partially resorbable by the body · CPC title

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title

• A61L2300/608

  having two or more layers · CPC title

• A61L27/34

  Macromolecular materials · CPC title