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

Patent metadata

Field	Value
Publication number	US-11898055-B2
Application number	US-202117495543-A
Country	US
Kind code	B2
Filing date	Oct 6, 2021
Priority date	Apr 3, 2013
Publication date	Feb 13, 2024
Grant date	Feb 13, 2024

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 substrate selected from the group comprising magnesium metal, magnesium alloy, iron metal, iron alloy, ferrous metal and ferrous alloy;
a pretreatment agent selected from the group consisting of alkali metal hydroxide, hydrogen fluoride, alkali metal carbonates, and mixtures thereof, applied to a surface of the 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:
at least one polymer layer comprising a first polymer and having a positive charge; and
at least one polymer layer comprising a second polymer and having a negative charge;

wherein an initial polymer layer of the plurality of interfacing, individual polymer layers is deposited on the charged substrate and has a charge opposite the charged substrate, and
wherein an outer polymer layer of the plurality of interfacing, individual polymer layers forms an exterior surface of the charged substrate;
fibronectin immobilized on the exterior surface; and
an active substance, in addition to the fibronectin, deposited on the exterior surface of the charged substrate.

2. The device of claim 1 , wherein the charged substrate is degradable.

3. The device of claim 1 , wherein the first polymer and the second polymer are each selected from the group consisting of natural polymer, synthetic polymer and mixtures thereof.

4. The device of claim 1 , wherein the first polymer and the second polymer are each selected from the group consisting of alginate, poly-L-lysine, poly(lactic-co-glycolic acid), polycaprolactone, poly(allylamine hydrochloride), polyacrylic acid, heparin, hyaluronic acid, polystyrene sulfonate, poly-L-glutamic acid, chitosan, polyethyleneimine, polydiallyldimethylammonium chloride and, mixtures and combinations thereof.

5. The device of claim 4 , wherein the first polymer and the second polymer are each selected from the group consisting of alginate and a mixture of poly-L-lysine and poly(lactic-co-glycolic acid).

6. The device of claim 4 , wherein the first polymer and the second polymer are each selected from the group consisting of polycaprolactone and poly(allylamine hydrochloride).

7. The device of claim 1 , wherein the first polymer and the second polymer are each in the form of a solution and deposition of the polyelectrolyte multilayer coating on the charged substrate comprises individually dipping the charged substrate into each of the first polymer solution and the second polymer solution.

8. 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.

9. 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 exterior surface of the charged substrate.

10. A coated medical implant device, comprising:
a substrate selected from the group comprising magnesium metal, magnesium alloy, iron metal, iron alloy, ferrous metal and ferrous alloy;
a pretreatment agent selected from the group consisting of alkali metal hydroxide, hydrogen fluoride, alkali metal carbonates, and mixtures thereof, applied to a surface of the 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 polymer layers having a positive charge; and
one or more polymer layers having a negative charge,

wherein an initial layer of the plurality of interfacing, individual polymer layers is deposited on the charged substrate and has a charge opposite the charged substrate, and
wherein the plurality of interfacing, individual polymer layers has alternating layers of the one or more polymer layers having a positive charge and the one or more polymer layers having a negative charge;
a chemical cross-linking agent deposited on an outer polymer layer forming 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.

11. A method of preparing a coating medical implant device, comprising:
selecting a substrate from the group comprising magnesium metal, magnesium alloy, iron metal, iron alloy, ferrous metal and ferrous alloy;
applying a pretreatment agent selected from the group consisting of alkali metal hydroxide, hydrogen fluoride, alkali metal carbonates, and mixtures thereof, to a surface of the substrate to form a charged substrate having a positive charge or negative charge; and
depositing a plurality of interfacing, individual polymer layers on the charged substrate to form a polyelectrolyte multilayer coating, comprising:
depositing at least one polymer layer comprising a first polymer and having a positive charge; and
depositing at least one polymer layer comprising a second polymer and having a negative charge,

wherein an initial polymer layer of the plurality of interfacing, individual polymer layers is deposited on the charged substrate and has a charge opposite the charged substrate, and
wherein an outer polymer layer of the plurality of interfacing, individual polymer layers forms an exterior surface of the charged substrate;
immobilizing fibronectin on the exterior surface; and
depositing an active substance, in addition to the fibronectin, on the exterior surface of the charged substrate.

12. The method of claim 11 , wherein the depositing a plurality of interfacing, individual polymer layers comprises individually dipping the charged substrate into each of a first polymer solution and a second polymer solution.

13. The method of claim 11 , further comprising depositing the active substance on one or more of the plurality of interfacing, individual polymer layers in addition to depositing on the exterior surface of the charged substrate.

14. The method of claim 11 , further comprising depositing a chemical cross-linking agent on the outer polymer layer forming a modified exterior outer surface.

15. The method of claim 14 , further comprising immobilizing the fibronectin on the modified exterior surface, in addition to the active substance.

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

• C09D177/04 Primary

  Polyamides derived from alpha-amino carboxylic acids (C09D177/10 takes precedence) · CPC title

• A61F2/02

  Prostheses implantable into the body · CPC title

• A61L27/04 Primary

  Metals or alloys · CPC title

• A61L27/34

  Macromolecular materials · CPC title

• A61L27/54

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