The present disclosure relates to wound dressings, and in particular to wound dressing based on cellulose acetate films containing binary metal oxide nanohybrids.
Numerous injuries, and particularly burns, require the application of some type of pad, gauze, cloth, dressing or similar covering (herein collectively called a “dressing”) to protect the wound while it is healing. Wounds, especially burns, sometimes have difficulty in healing and are frequently prone to infection because natural protective skin barriers are disrupted and are slow in repairing themselves. The most commonly used dressing material has been cotton because it is both inexpensive and readily available. However, as those who have used cotton dressings are aware, they tend to stick to the injured area, even when the surface of the area is covered with a lubricant such as petroleum jelly (“petrolatum”) or similar substance, or a medicinal agent which contains a lubricant.
Developments in the medical arts have resulted in some improvements in medical dressings, two of which are represented by Johnson & Johnson's ADAPCTIC™ brand non-adherent dressings and the Curity® brand TELFA® sterile pads sold by Kendall-Futuro Company. The ADAPTIC™ brand dressing was found to consist of a cellulose acetate pad which has been soaked in petrolatum or similar substance to impart anti-adhesion properties. While the petrolatum reduces adhesion to a wound, it's use results in a pad that is greasy and messy to handle compared to a pad without petrolatum. The TELFA® dressing consists of a polyethylene terephthalate (PET) shell and a caustic washed cotton insert, the anti-adhesion properties being imparted by the PET shell.
Current dressings, while having various qualities which may reduce adhesion or provide other benefits, typically incorporate lubricants and/or fluids or fluid releasing agents and use fibers other than cellulose acetate to provide non-adhesion properties.
While certain current dressings represent improvements in reducing dressing adhesion to wounds, further improvements in the field are highly desirous. In particular, an improved dressing of cellulose acetate would be useful in the medical arts because cellulose acetate is both chemotactic for attracting white blood cells and hydrophilic. The white cell chemotactic property of cellulose acetate fibers is desirable in a wound dressing because white blood cells aid in fighting infection. The hydrophilic property is desirable because it aids in removing excess fluids which may ooze from the surface of a wound during the healing process.
Thus, new wound dressings solving the aforementioned problems are desired.
The present subject matter relates to cellulose acetate, silver-vanadate, and/or gadolinium trioxide wound dressing nano-films. In particular, the present wound dressings comprise a cellulose acetate film comprising cellulose acetate and silver vanadate and/or gadolinium trioxide nanoparticles within a cellulose acetate matrix. Different weights of these substances can be chosen during manufacture to achieve a certain morphological appearance. These multifunctional wound dressing films could be a promising and potential option for wound healing.
In an embodiment, the present subject matter relates to a wound dressing comprising a cellulose acetate film comprising: cellulose acetate; and nanoparticles selected from the group consisting of silver vanadate nanoparticles, gadolinium trioxide nanoparticles, and combinations thereof.
In another embodiment, the present subject matter relates to a method for making a cellulose acetate-based film, the method comprising: dissolving cellulose acetate and nanoparticles selected from the group consisting of silver vanadate nanoparticles, gadolinium trioxide nanoparticles, and combinations thereof in acetone to obtain a solution; resting the solution in a sealed glass container at about 298 K for at least about 24 hours; stirring the solution for at least about 2 hours; placing the solution onto a glass plate; and evaporating the acetone to obtain the cellulose acetate-based film.
In a further embodiment, the present subject matter relates to a method of healing a wound in a patient comprising applying to a patient in need thereof a wound dressing as described herein at a site of the wound in the patient.
These and other features of the present subject matter will become readily apparent upon further review of the following specification.
The following definitions are provided for the purpose of understanding the present subject matter and for construing the appended patent claims.
Throughout the application, where compositions are described as having, including, or comprising specific components, or where processes are described as having, including, or comprising specific process steps, it is contemplated that compositions of the present teachings can also consist essentially of, or consist of, the recited components, and that the processes of the present teachings can also consist essentially of, or consist of, the recited process steps.
It is noted that, as used in this specification and the appended claims, the singular forms “a”, “an”, and “the” include plural references unless the context clearly dictates otherwise.
In the application, where an element or component is said to be included in and/or selected from a list of recited elements or components, it should be understood that the element or component can be any one of the recited elements or components, or the element or component can be selected from a group consisting of two or more of the recited elements or components. Further, it should be understood that elements and/or features of a composition or a method described herein can be combined in a variety of ways without departing from the spirit and scope of the present teachings, whether explicit or implicit herein.
The use of the terms “include,” “includes”, “including,” “have,” “has,” or “having” should be generally understood as open-ended and non-limiting unless specifically stated otherwise.
The use of the singular herein includes the plural (and vice versa) unless specifically stated otherwise. In addition, where the use of the term “about” is before a quantitative value, the present teachings also include the specific quantitative value itself, unless specifically stated otherwise. As used herein, the term “about” refers to a ±10% variation from the nominal value unless otherwise indicated or inferred.
The term “optional” or “optionally” means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances in which it does not.
It will be understood by those skilled in the art with respect to any chemical group containing one or more substituents that such groups are not intended to introduce any substitution or substitution patterns that are sterically impractical and/or physically non-feasible.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which the presently described subject matter pertains.
Where a range of values is provided, for example, concentration ranges, percentage ranges, or ratio ranges, it is understood that each intervening value, to the tenth of the unit of the lower limit, unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the described subject matter. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges, and such embodiments are also encompassed within the described subject matter, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the described subject matter.
Throughout the application, descriptions of various embodiments use “comprising” language. However, it will be understood by one of skill in the art, that in some specific instances, an embodiment can alternatively be described using the language “consisting essentially of” or “consisting of”.
“Subject” as used herein refers to any animal classified as a mammal, including humans, domestic and farm animals, and zoo, sports, and pet companion animals such as household pets and other domesticated animals such as, but not limited to, cattle, sheep, ferrets, swine, horses, poultry, rabbits, goats, dogs, cats and the like.
“Patient” as used herein refers to a subject in need of treatment of a condition, disorder, or disease, such as an acute or chronic airway disorder or disease.
For purposes of better understanding the present teachings and in no way limiting the scope of the teachings, unless otherwise indicated, all numbers expressing quantities, percentages or proportions, and other numerical values used in the specification and claims, are to be understood as being modified in all instances by the term “about”. Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained. At the very least, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.
In an embodiment, the present subject matter relates to a wound dressing comprising a cellulose acetate film comprising: cellulose acetate; and nanoparticles selected from the group consisting of silver vanadate nanoparticles, gadolinium trioxide nanoparticles, and combinations thereof.
In one embodiment of the present wound dressings, the nanoparticles can be silver vanadate nanoparticles. In this regard, the silver vanadate nanoparticles can have a particle size of about 10 to about 25 nm, or of about 12.3 nm. In another embodiment of the present wound dressings, the nanoparticles can be gadolinium trioxide nanoparticles. In this regard, the gadolinium trioxide nanoparticles can have a particle size of about 180 to about 200 nm, or of about 191 nm. In one more embodiment of the present wound dressings, the nanoparticles can be a combination of silver vanadate nanoparticles and gadolinium trioxide nanoparticles. In this binary metal oxide embodiment, the gadolinium trioxide nanoparticles can have a particle size of about 315 nm to about 335 nm, or of about 324 nm.
In a further embodiment, the cellulose acetate film can have a homogenous spread of pores on it surface.
As shown in
In an embodiment, the silver vanadate (Ag3VO4) nanoparticles and/or the gadolinium trioxide (Gd2O3) nanoparticles can be encapsulated within the cellulose acetate. The addition of these nanoparticles may lead to an enhancement in the biological activity of cellulose acetate (CA) films.
In certain embodiments, the present wound dressings may comprise one or more further excipients, carriers, or vehicles. Non-limiting examples of suitable excipients, carriers, or vehicles useful herein include liquids such as water, saline, glycerol, polyethyleneglycol, hyaluronic acid, ethanol, and the like. Suitable excipients for nonliquid formulations are also known to those of skill in the art. A thorough discussion of therapeutically acceptable excipients and salts useful herein is available in Remington's Pharmaceutical Sciences, 18th Edition. Easton, Pa., Mack Publishing Company, 1990, the entire contents of which are incorporated by reference herein.
The present wound dressings typically contain a therapeutically effective dosage, e.g., a dosage sufficient to promote wound healing.
While human dosage levels have yet to be optimized for the present wound dressings, generally, a single wound dressing may contain from about 0.01 to 10.0 mg/kg of body weight, for example about 0.1 to 5.0 mg/kg of body weight. The precise effective amount will vary from subject to subject and will depend upon the species, age, the subject's size and health, the nature and extent of the condition being treated, recommendations of the treating physician, and the therapeutics or combination of therapeutics selected for administration. The subject may be administered as many wound dressings as is required to reduce and/or alleviate the wound.
The present wound dressings have valuable therapeutic properties, which make them commercially utilizable.
In another embodiment, the present subject matter relates to a method for making a cellulose acetate-based film, the method comprising: dissolving cellulose acetate and nanoparticles selected from the group consisting of silver vanadate nanoparticles, gadolinium trioxide nanoparticles, and combinations thereof in acetone to obtain a solution; resting the solution in a sealed glass container at about 298 K for at least about 24 hours; stirring the solution for at least about 2 hours; placing the solution onto a glass plate; and evaporating the acetone to obtain the cellulose acetate-based film.
In certain embodiments in this regard, the cellulose acetate can be dissolved in the acetone in a ratio of about 1:10 (m/v).
In a further embodiment, the present subject matter relates to a method of healing a wound in a patient comprising applying to a patient in need thereof a wound dressing as described herein at a site of the wound in the patient.
In certain embodiments in this regard, the wound dressing can include the silver vanadate nanoparticles, and vanadate from the silver vanadate nanoparticles can encourage endothelial cells to occupy collagen matrices and arrange into tubules, stimulate cell proliferation, or stimulate bone collagen formation at the site of the wound in the patient.
In another embodiment, application of the wound dressing can promote metabolite circulation and vascularization.
In one embodiment of the present methods, the wound dressing can include the gadolinium trioxide nanoparticles, which release oxonium ions (H3O+) in use, thereby disrupting cellular pH and preventing development of drug resistance in the patient.
In another embodiment of the present methods, the wound dressing can include the silver vanadate nanoparticles and the gadolinium trioxide nanoparticles. According to certain of these embodiments, the wound dressing can promote wound healing through a heightened ability of the cellulose acetate film to adhere to a surface of the wound.
In the above methods, the patient is preferably a mammal, more preferably a human. Furthermore, the present wound dressing can be used in combination therapy with one or more additional therapeutic agents.
The following examples relate to various methods of manufacturing certain specific wound dressings and their use as described herein.
Preparation of Silver Vanadate (Ag3VO4)
Sodium orthovanadate (Na3VO4) and silver chloride (AgCl) were obtained from PubChem. The co-precipitation method was used to prepare silver vanadate according to the following equation:
3AgCl+Na3VO4→3NaCl+Ag3VO4
To prepare Ag3VO4, about 5 g of AgCl was dissolved in deionized water, and 2.14 g of Na3VO4 was dissolved in another beaker at 343.15 K till the solution become clear. Then, the Na3VO4 solution was dropped wisely over the solution of AgCl and a few drops of NaCl was added to the solution to adjust the pH. After that, the precipitated powder was washed 4 times and then dried in a drier furnace. Finally, the powder was ground with a mortar, and Ag3VO4 nanoparticles were obtained.
Preparation of Cellulose Acetate Film with Various Oxide Concentrations
Silver-vanadate, gadolinium oxide, and cellulose acetate (CA) were bought from PubChem. Casting methodology helped create the CA films.
CA was dissolved in acetone at a ratio of 1:10 (m/v) with the powder (silver-vanadate and/or gadolinium oxide) components to create a film-genic solution, which then rested for 24 hours at 298 K in a sealed glass. After that, the solution was magnetically stirred for 2 hours. The mixture was put onto a glass plate and allowed to sit there until the solvent had completely evaporated. The first film was prepared from pure CA, while the other films were prepared by adding the nanoparticles to the CA solution with determined concentrations. The name of the cellulose acetate film was FAC.
Films made of cellulose acetate were structurally investigated by XRD data. As can be seen in
Without any proof of the existence of separated silver metal, the a and B phases are indexed to the cards (JCPDS 19-1151), and (JCPDS 29-1154), respectively. The peak of excess silver in silver vanadate-containing films is positioned at 38.4°. Peaks confirm the coexistence of silver vanadate's major phase β and minor phase α, respectively.
The primary peaks of Gd2O3 are seen at 28.6, 33.1, 47.3, and 56.2°, which correspond to unit cell planes (222), (400), (440), and (622). The XRD diffraction graph (
In terms of FTIR spectra, as shown in
As a result,
Through EDX analysis, as seen in
SEM micrographs as shown in
The average of contact angles for pure CA, Ag3VO4@CA, Gd2O3@CA, and Ag3VO4/Gd2O3@CA films are 41.5±0.875, 46.4±0.345, 40.6±1.035, and 40.6±0.09°, as shown in
Cell Viability Percentage Upon the Utilization of Ag3VO4/Gd2O3@CA Against Normal Lung Cells
The impact of Ag3VO4/Gd2O3@CA on normal cell line viability was studied. Ag3VO4/Gd2O3@CA concentrations are plotted against normal cell lines viability in
According to IORDACHESCU et al. (2002), vanadate has a variety of effects that depend on the exposure level. Vanadate exhibits a mitogenic tendency at low concentrations, to a maximal level at 100 μM, acting as a growth factor. Vanadate, however, exhibits obvious decreases in cell viability and proliferation at high concentrations, suggesting that cytotoxicity is caused by the release of reactive oxygen species. Epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) play critical roles in wound healing. Briefly, vanadate has been shown to mirror the effects of fibroblast growth factor in that it encourages endothelial cells to occupy collagen matrices and arrange into tubules. It also stimulates cell proliferation and bone collagen formation in vitro. In fact, the topological characteristics of the composition examined, such as porosity, strongly influence the interaction mechanism between the injured tissues and the implant film.
The high porosity surface promotes metabolite circulation and vascularization. The degree of roughness and wettability also have a direct impact on the biological performance of the film. Furthermore, the number, size, and distribution of the implanted silver have an impact on the efficiency of the released reactive oxy-species. Additionally, the cellular pH is disrupted due to the released oxonium ions (H3O+) from Gd2O3 mineral trioxide, which also prevents the development of drug resistance.
In general, surface morphology, type, and quantity of composition constituents play a significant role in the potential for bio-applicability; as a result, they are the tools to modify the physical and chemical properties of the created film composite. As a result, the insertion of silver-vanadate and gadolinium trioxide promotes healing indirectly by improving the ability of the produced nano-films composition to adhere to the surface of live tissues.
It is to be understood that the wound dressings are not limited to the specific embodiments described above, but encompasses any and all embodiments within the scope of the generic language of the following claims enabled by the embodiments described herein, or otherwise shown in the drawings or described above in terms sufficient to enable one of ordinary skill in the art to make and use the claimed subject matter.
Number | Date | Country | |
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Parent | 18221957 | Jul 2023 | US |
Child | 18526914 | US |