Methods for Producing Stable Hydrophilic Optically Clear Biocompatible Coating Using

Plasma Grafting

Cross-Reference to Related Application

[0001] This application claims priority of U.S. Provisional Patent Application No.

62/508,349, filed May 18, 2017, the entire contents of which are incorporated by reference herein.

Field of the Invention

[0002] The present invention discloses methods for producing a stable hydrophilic, optically clear, and biocompatible coating for hydrophobic substrates such as silicone elastomer using glow discharge plasma grafting of poly(ethylene glycol) (PEG) compounds. The PEG molecules are ionized in a glow discharge plasma driven by an electric field and covalently attach to with the substrate surfaces. Advantageously, such methods produce a stable hydrophilic, optically clear, and biocompatible surface.

Background of the Invention

[0003] Surfaces covered with polyethylene glycol) (PEG; HO-(CH2-CH2-0)n-

H) have been shown to be biocompatible because PEG's properties yield non- immunogenicity, non-antigenicity, and protein rejection. PEG hydrogels are currently approved by the FDA for clinical use on various medical devices. Several other synthetic polymers (PHEMA, PVA) have also been developed for medical applications, but by far, PEG hydrogels are the most extensively characterized historically. It has been shown that PEG hydrogels are non-immunogenic, resist protein absorption and cell absorption and are non-cytotoxic. In addition, PEG hydrogels have been shown to dramatically reduce friction for devices that are inserted, like catheters.

[0004] Methods of PEG polymer coating include passive or covalent attachment of the PEG polymer on the surface. In the passive coating methods, PEG polymers are conjugated to proteins or other polymers that facilitate the adsorption onto biomaterial surfaces [for example, see Ruiz-Taylor, L. A., et al. "Monolayers of derivatized poly (L- lysine)-grafted poly (ethylene glycol) on metal oxides as a class of biomolecular interfaces." Proceedings of the National Academy of Sciences 98.3 (2001): 852-857.]. Passive coating is performed by contacting the substrate surface with coating solutions, using processes such as spray coating or dip coating. The passive coating methods have the advantage of being easy to manufacture; but have the disadvantage of being less durable. The coated layer is prone to dissociation in the in vivo environment.

[0005] In the prior art covalent coating methods, PEG polymers bearing chemically reactive group are synthesized and covalently attached to the chemically reactive groups on the surface. This requires the presence of chemically reactive groups (such as amine or carboxyl functional groups) on the surface for attachment. As these groups are not present in most common biomaterials, an additional surface "priming" step is performed to impart functional groups on the surface by surface modification methods such as photochemistry, plasma treatment or plasma polymerization (for example, see US 2008/0208334 Al). Therefore, the prior art covalent coating processes contain several steps that induce higher manufacturing cost. In some methods, organic solvents or toxic chemicals are used in the reactions, making the methods unsuitable for some biomaterials.

[0006] In the prior art covalent coating methods, there is only a single layer of the

PEG molecule attached to the surface. The thickness of the PEG layer is determined by the size of the PEG molecule and is usually limited to nanometer scale. The thin layer of PEG coating is susceptible to pin holes due to incomplete coatings. The pin holes can provide binding sites for biomolecules and micro-organisms and therefore reduce the antifouling performance. Since there is only one covalent attachment point per PEG molecule, the breakage of the attachment point (e.g, by hydrolysis or reduction) will dissociate the PEG molecule and expose original surface, thus forming a pin hole. Therefore, the durability of the prior art covalent PEG coating is limited due to the single layer of PEG molecules and the single point attachment for each PEG molecule.

Summary of the Invention

[0007] A method is disclosed herein for producing a stable hydrophilic, optically transparent and biocompatible surface using glow discharge plasma grafting of PEG compounds. The PEG compounds used in the plasma grafting preferably have a molecular weight higher than 300 Dalton. The molecules of the PEG compounds are ionized by the glow discharge plasma driven by an electric field and react with the substrate surfaces.

[0008] One advantage of the disclosed method is that the hydrophilicity of the coated surface can be preserved for a very long time with minimum hydrophobic recovery. This is due to the plasma grafting method, which creates stable covalent bond between the PEG polymer and the substrate surface.

[0009] Another advantage of the disclosed method is that the coating does not affect the optical clarity of the substrates, such as contact lenses when higher molecular weight PEG compounds are used for plasma grafting.

[0010] A further advantage of the disclosed method is that the hydrophilic coating is formed in a dry state without the use of any solvent. This is advantageous for coating devices with electronic and/or biosensing components.

[0011] These and other features of the invention will be better understood through a study of the following detailed description and accompanying drawings.

Brief Description of the Figures

[0012] FIG. 1 is a flowchart representing a method in accordance with the subject invention.

[0013] FIG. 2 is a chart comparing the water contact angle of silicone contact lenses coated with plasma grafted PEG of different molecular weight.

[0014] FIG. 3 is a chart comparing the light transmittance at 550 nm of silicone contact lenses coated with plasma grafted PEG of different molecular weight.

[0015] FIG. 4 is a chart comparing the water contact angle of silicone contact lenses coated with prior art oxygen plasma treatment method and silicone contact lenses coated with subject invention method of plasma grafted PEG, after the lenses were stored in air for a period of time.

Detailed Description of the Invention

[0016] The present invention discloses methods for producing a hydrophilic, optically transparent and biocompatible surface using glow discharge plasma grafting of PEG compounds. The PEG compounds used in the plasma grafting preferably have a molecular weight higher than 300 Dalton. The molecules of the PEG compounds are ionized by the glow discharge plasma driven by an electric field and react with the substrate surfaces. Preferably, the PEG compounds used in this method have molecular formula Ri(OCH ₂ CH ₂ )nOR ₂ , where Ri = H or CH ₃ and R ₂ = H or CH ₃ . Preferably, n > 7; as n =7 correspond to a molecular weight of 300 Dalton.

[0017] Any known technique can be used to generate glow discharge plasma. The glow discharge plasma may be generated using AC or DC power, radio-frequency (RF) power or micro-wave frequency power. Preferably, the plasma system is driven by a single radio-frequency (RF) power supply; typically at 13.56 MHz. The plasma system can either be capacitively coupled plasma, or inductively coupled plasma. Preferably, A matching network consisting of capacitors and inductors is used to minimize the reflected power from the electrodes.

[0018] The substrate may be made of any materials, including polymers, glass, metal and silicon. Examples of polymers include polystyrene, polypropylene, polyethylene, polyester, silicone, polyurethane, ABS, PVC, polytetrafluoroethylene, polyvinylidene, and mixtures thereof. In one example, the substrates are silicone contact lens.

EXAMPLES

Example A

[0019] Silicone contact lenses are coated in a radiofrequency glow discharge plasma chamber in the presence of the chemical vapors of PEG molecules with different average molecular weights. Glow discharge plasma is initiated by applying a 13.56 MHz radiofrequency power to the capacitively coupled electrodes inside the chamber. A matching network consisting of capacitors and inductors is used to minimize the reflected power from the electrodes. The radiofrequency power is first set at 100 W for 5 minutes and then adjusted to 20 W for 30 minutes. After the glow discharge plasma grafting process is completed, the chamber is filled with air and the coated silicone contact lenses are retrieved.

Example B

[0020] The hydrophilicity of the silicone contact lenses coated in Example A were compared using water contact angle measurement. Each coated lens was rinsed with water and dried with air before contact angle measurement using a goniometer. As can be seen in FIG. 2, the uncoated lens has a contact angle of 110° (hydrophobic), while all coated lenses have contact angles below 70° (hydrophilic). Plasma grafting coating using higher molecular weight PEG (> 300 Dalton, average n > 6) results in significantly lower water contact angle (more hydrophilic).

Example C

[0021] The optical clarity of the silicone contact lenses coated in Example A were compared using light transmittance measurement. Each coated lens was placed in a quartz cuvette filled with water. Light transmittance at 550 nm through the lens soaked in water for 30 minutes was measured by an UV-Vis spectrometer. As can be seen in FIG. 3, the light transmittance was reduced significantly for the lenses coated with low molecular weight PEG. Plasma grafting coating using higher molecular weight PEG (> 300 Dalton, average n > 6) results in much better transparency (light transmittance close to uncoated lenses).

Example D

[0022] Silicone contact lenses are coated in a radiofrequency glow discharge plasma chamber in the presence of the chemical vapors of PEG molecules with average molecular weight of 400 Dalton. Glow discharge plasma is initiated by applying a 13.56 MHz radiofrequency power to the capacitively coupled electrodes inside the chamber. A matching network consisting of capacitors and inductors is used to minimize the reflected power from the electrodes. The radiofrequency power is first set at 100 W for 5 minutes and then adjusted to 20 W for 30 minutes. After the glow discharge plasma grafting process is completed, the chamber is filled with air and the coated silicone contact lenses are retrieved.

Example E

[0023] Silicone contact lenses coated in Example D were compared with silicone contact lenses coated with prior art oxygen plasma treatment method for hydrophobic recovery when stored in air for a prolonged period of time. As can be seen in FIG. 4, on the first day both silicone substrates demonstrated hydrophilicity with similar small water contact angles. The silicone contact lenses coated with prior art oxygen plasma treatment method underwent hydrophobic recovery and the contact angle increased to about 90 degrees after 10 days of storage, while the silicone contact lenses coated with subject invention plasma grafting method remained hydrophilic with contact angle unchanged for over 100 days.

[0024] As will be appreciated by those skilled in the art, the subject invention can be used to produce an optically clear, hydrophilic and biocompatible coating. The present teachings can be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The foregoing embodiments are therefore to be considered in all respects illustrative rather than limiting on the present teachings described herein. The scope of the present teachings is thus indicated by the appended claims rather than by the foregoing description, and all changes that come within the meaning and range of equivalency of the claims are intended to be embraced therein.