FORMULATION AND METHOD FOR TREATING ALZHEIMER'S DISEASE USING LIPOSOMAL PYRAZOLONE DERIVATIVE

Abstract

Disclosed herein is a formulation and method for treating Alzheimer’s disease using liposomal pyrazolone derivative (100) that comprises a liposomal encapsulation of the pyrazolone derivative, wherein the liposome is configured to enhance the stability and bioavailability of the pyrazolone derivative, phospholipids selected from the group consisting of phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine, wherein the phospholipids contribute to the structural integrity of the liposomal formulation and facilitate the encapsulation process, cholesterol, wherein the cholesterol is incorporated to modulate the fluidity and permeability of the liposomal membrane, ensuring the controlled release of the pyrazolone derivative, chitosan, wherein the chitosan is used as a stabilizing agent to enhance the mucoadhesive properties of the liposomal formulation, a targeting moiety selected from the group consisting of antibodies, peptides, or small molecules, wherein the targeting moiety is attached to the surface of the liposome to facilitate the targeted delivery of the pyrazolone derivative to neuronal cells.

Specification

Description:FIELD OF DISCLOSURE
[0001] The present disclosure generally relates to the field of pharmaceuticals, more specifically, relates to formulation and method for treating Alzheimer's disease using a liposomal pyrazolone derivative.
BACKGROUND OF THE DISCLOSURE
[0002] The liposomal formulation improves the bioavailability of the pyrazolone derivative, allowing for better absorption and delivery to the brain. This leads to increased efficacy in treating Alzheimer's disease.
[0003] The liposomal delivery system can potentially reduce the side effects associated with traditional drug administration, improving patient tolerability and compliance.
[0004] The combination of the pyrazolone derivative and the liposomal carrier may exhibit synergistic effects, enhancing the therapeutic efficacy and potentially addressing multiple targets involved in Alzheimer's disease.
[0005] Many current treatments for Alzheimer's disease offer only modest improvements in symptoms and do not address the underlying causes of the disease, leading to a limited long-term benefit and a continued decline in cognitive function.
[0006] Existing medications can have significant side effects, such as gastrointestinal issues, nausea, and dizziness, which can reduce patient compliance and quality of life. These side effects can also interfere with daily activities and negatively impact the overall well-being of patients.
[0007] Most current treatments are symptomatic and do not modify the disease progression, leading to a limited long-term benefit. Patients with Alzheimer's disease continue to experience a progressive decline in cognitive function despite treatment, highlighting the need for innovative approaches that can target the underlying causes of the disease.
[0008] Thus, in light of the above-stated discussion, there exists a need for a formulation and method for treating Alzheimer's disease using liposomal pyrazolone derivative.
SUMMARY OF THE DISCLOSURE
[0009] The following is a summary description of illustrative embodiments of the invention. It is provided as a preface to assist those skilled in the art to more rapidly assimilate the detailed design discussion which ensures and is not intended in any way to limit the scope of the claims which are appended hereto in order to particularly point out the invention.
[0010] According to illustrative embodiments, the present disclosure focuses on a formulation and method for treating Alzheimer's disease using liposomal pyrazolone derivative which overcomes the above-mentioned disadvantages or provide the users with a useful or commercial choice.
[0011] An objective of the present disclosure is to develop a novel therapeutic approach for Alzheimer's disease that addresses the limitations of existing treatments, offering a promising new option for patients and healthcare providers.
[0012] Another objective of the present disclosure is to create a liposomal formulation of a pyrazolone derivative that enhances drug delivery to the brain, overcoming the challenges associated with traditional drug administration and improving therapeutic efficacy.
[0013] Another objective of the present disclosure is to provide a treatment option for Alzheimer's disease that exhibits reduced side effects compared to traditional medications, improving patient tolerability and quality of life, and enabling long-term adherence to the treatment regimen.
[0014] Another objective of the present disclosure is to develop a therapeutic agent that can potentially modify the course of Alzheimer's disease, slowing down its progression and improving cognitive function for patients, thereby enhancing their overall quality of life and independence.
[0015] Another objective of the present disclosure is to offer a more affordable and accessible treatment option for Alzheimer's disease patients, expanding access to care and reducing the financial burden on individuals and families affected by the disease.
[0016] Another objective of the present disclosure is to improve the quality of life for individuals suffering from Alzheimer's disease by alleviating cognitive symptoms, enhancing daily functioning, and supporting overall well-being.
[0017] Another objective of the present disclosure is to contribute to advancements in the treatment of neurodegenerative disorders, providing hope for patients and their families and paving the way for future breakthroughs in brain health research.
[0018] Another objective of the present disclosure is to explore innovative drug delivery strategies that can overcome the challenges associated with targeting the brain, ensuring that the therapeutic agent reaches the intended site of action and exerts its beneficial effects.
[0019] Another objective of the present disclosure is to develop a therapeutic agent with a favourable safety and tolerability profile, minimizing adverse effects and ensuring patient comfort and compliance with the treatment regimen.
[0020] Yet another objective of the present disclosure is to contribute to the development of personalized medicine approaches for Alzheimer's disease, tailoring treatments to individual patient needs and maximizing treatment effectiveness.
[0021] In light of the above, in one aspect of the present disclosure, a formulation for treating Alzheimer's disease using liposomal pyrazolone derivative is disclosed herein. The formulation comprises a liposomal encapsulation of the pyrazolone derivative, wherein the liposome is configured to enhance the stability and bioavailability of the pyrazolone derivative. The formulation includes phospholipids selected from the group consisting of phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine, wherein the phospholipids contribute to the structural integrity of the liposomal formulation and facilitate the encapsulation process. The formulation also includes cholesterol, wherein the cholesterol is incorporated to modulate the fluidity and permeability of the liposomal membrane, ensuring the controlled release of the pyrazolone derivative. The formulation also includes chitosan, wherein the chitosan is used as a stabilizing agent to enhance the mucoadhesive properties of the liposomal formulation. The formulation also includes a targeting moiety selected from the group consisting of antibodies, peptides, or small molecules, wherein the targeting moiety is attached to the surface of the liposome to facilitate the targeted delivery of the pyrazolone derivative to neuronal cells.
[0022] In one embodiment, the pyrazolone derivative is selected from the group consisting of antipyrine, aminopyrine, dipyrone, or any combination thereof.
[0023] In one embodiment, the phospholipids are derived from natural sources such as soy lecithin or egg yolk, enhancing the biocompatibility of the liposomal formulation.
[0024] In one embodiment, the liposome has a size range between 50 to 200 nanometres, optimizing the penetration across the blood-brain barrier.
[0025] In one embodiment, the targeting moiety is conjugated to the liposome at a ratio of 1-5 molecules of the targeting agent per liposome, ensuring optimal targeting efficiency and specificity in delivering the pyrazolone derivative to neuronal cells.
[0026] In one embodiment, the cholesterol to phospholipid ratio is between 1:1 and 1:2, providing an optimal balance between membrane fluidity and rigidity.
[0027] In one embodiment, the phospholipids constitute 40-60% of the total lipid content in the liposomal formulation, optimizing the structural integrity and encapsulation efficiency of the pyrazolone derivative.
[0028] In one embodiment, the cholesterol is present at a concentration of 10-20% of the total lipid content, which is specifically calibrated to modulate the membrane fluidity and permeability, ensuring controlled and sustained release of the pyrazolone derivative.
[0029] In one embodiment, the chitosan is included at a concentration of 0.5-5% of the total formulation weight, providing enhanced stability, mucoadhesive properties, and improved bioavailability of the pyrazolone derivative for treating Alzheimer's disease.
[0030] In light of the above, in one aspect of the present disclosure, a method for treating Alzheimer's disease using liposomal pyrazolone derivative is disclosed herein. The method comprises encapsulating a pyrazolone derivative within the liposomes using a solvent evaporation technique, wherein the liposomes are configured to enhance the stability and bioavailability of the pyrazolone derivative. The method includes incorporating phospholipids selected from the group consisting of phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine into the liposome structure, wherein the phospholipids contribute to the structural integrity of the liposomal formulation and facilitate the encapsulation process. The method also includes adding cholesterol to the liposomal mixture, wherein the cholesterol modulates the fluidity and permeability of the liposomal membrane, ensuring a controlled and sustained release of the pyrazolone derivative. The method also includes the incorporation of chitosan as a stabilizing agent in the liposomal formulation, wherein the chitosan enhances the mucoadhesive properties of the liposomes. The method also includes attaching a targeting moiety selected from the group consisting of antibodies, peptides, or small molecules to the surface of the liposome, wherein the targeting moiety facilitates the targeted delivery of the pyrazolone derivative to neuronal cells.
[0031] These and other advantages will be apparent from the present application of the embodiments described herein.
[0032] The preceding is a simplified summary to provide an understanding of some embodiments of the present invention. This summary is neither an extensive nor exhaustive overview of the present invention and its various embodiments. The summary presents selected concepts of the embodiments of the present invention in a simplified form as an introduction to the more detailed description presented below. As will be appreciated, other embodiments of the present invention are possible utilizing, alone or in combination, one or more of the features set forth above or described in detail below.
[0033] These elements, together with other aspects of the present disclosure and various features are pointed out with particularity in the claims annexed hereto and form a part of the present disclosure. For a better understanding of the present disclosure, its operating advantages, and the specified object attained by its uses, reference should be made to the accompanying drawings and descriptive matter in which there are illustrated exemplary embodiments of the present disclosure.
BRIEF DESCRIPTION OF THE DRAWINGS
[0034] To describe the technical solutions in the embodiments of the present disclosure or in the prior art more clearly, the following briefly describes the accompanying drawings required for describing the embodiments or the prior art. Apparently, the accompanying drawings in the following description merely show some embodiments of the present disclosure, and a person of ordinary skill in the art can derive other implementations from these accompanying drawings without creative efforts. All of the embodiments or the implementations shall fall within the protection scope of the present disclosure.
[0035] The advantages and features of the present disclosure will become better understood with reference to the following detailed description taken in conjunction with the accompanying drawing, in which:
[0036] FIG. 1 illustrates a flowchart of a formulation for treating Alzheimer's disease using liposomal pyrazolone derivative, in accordance with an exemplary embodiment of the present disclosure;
[0037] FIG. 2 illustrates a flowchart of a method for treating Alzheimer's disease using liposomal pyrazolone derivative, in accordance with an exemplary embodiment of the present disclosure;
[0038] FIG. 3 illustrates a step-by-step of the working model of a formulation and method for treating Alzheimer's disease using liposomal pyrazolone derivative, in accordance with an exemplary embodiment of the present disclosure.
[0039] Like reference, numerals refer to like parts throughout the description of several views of the drawing.
[0040] The formulation and method for treating Alzheimer's disease using liposomal pyrazolone derivative is illustrated in the accompanying drawings, which like reference letters indicate corresponding parts in the various figures. It should be noted that the accompanying figure is intended to present illustrations of exemplary embodiments of the present disclosure. This figure is not intended to limit the scope of the present disclosure. It should also be noted that the accompanying figure is not necessarily drawn to scale.
DETAILED DESCRIPTION OF THE DISCLOSURE
[0041] The following is a detailed description of embodiments of the disclosure depicted in the accompanying drawings. The embodiments are in such detail as to communicate the disclosure. However, the amount of detail offered is not intended to limit the anticipated variations of embodiments; on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure.
[0042] In the following description, numerous specific details are set forth in order to provide a thorough understanding of the embodiments of the present disclosure. It may be apparent to one skilled in the art that embodiments of the present disclosure may be practiced without some of these specific details.
[0043] Various terms as used herein are shown below. To the extent a term is used, it should be given the broadest definition persons in the pertinent art have given that term as reflected in printed publications and issued patents at the time of filing.
[0044] The terms "a" and "an" herein do not denote a limitation of quantity, but rather denote the presence of at least one of the referenced items.
[0045] The terms "having", "comprising", "including", and variations thereof signify the presence of a component.
[0046] Referring now to FIG. 1 to FIG. 3 to describe various exemplary embodiments of the present disclosure. FIG. 1 illustrates a flowchart of a formulation for treating Alzheimer's disease using liposomal pyrazolone derivative 100, in accordance with an exemplary embodiment of the present disclosure.
[0047] The formulation 100 may include a liposomal encapsulation of the pyrazolone derivative, wherein the liposome is configured to enhance the stability and bioavailability of the pyrazolone derivative. The formulation 100 may include phospholipids selected from the group consisting of phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine, wherein the phospholipids contribute to the structural integrity of the liposomal formulation and facilitate the encapsulation process. The formulation 100 may also include cholesterol, wherein cholesterol is incorporated to modulate the fluidity and permeability of the liposomal membrane, ensuring the controlled release of the pyrazolone derivative. The formulation 100 may also include chitosan, wherein the chitosan is used as a stabilizing agent to enhance the mucoadhesive properties of the liposomal formulation. The formulation 100 may also include a targeting moiety selected from the group consisting of antibodies, peptides, or small molecules, wherein the targeting moiety is attached to the surface of the liposome to facilitate the targeted delivery of the pyrazolone derivative to neuronal cells.
[0048] The pyrazolone derivative is selected from the group consisting of antipyrine, aminopyrine, dipyrone, or any combination thereof.
[0049] The phospholipids are derived from natural sources such as soy lecithin or egg yolk, enhancing the biocompatibility of the liposomal formulation.
[0050] The liposome has a size range between 50 to 200 nanometres, optimizing the penetration across the blood-brain barrier.
[0051] The targeting moiety is conjugated to the liposome at a ratio of 1-5 molecules of the targeting agent per liposome, ensuring optimal targeting efficiency and specificity in delivering the pyrazolone derivative to neuronal cells.
[0052] The cholesterol-to-phospholipid ratio is between 1:1 and 1:2, providing an optimal balance between membrane fluidity and rigidity.
[0053] The phospholipids constitute 40-60% of the total lipid content in the liposomal formulation, optimizing the structural integrity and encapsulation efficiency of the pyrazolone derivative.
[0054] Cholesterol is present at a concentration of 10-20% of the total lipid content, which is specifically calibrated to modulate the membrane fluidity and permeability, ensuring controlled and sustained release of the pyrazolone derivative.
[0055] The chitosan is included at a concentration of 0.5-5% of the total formulation weight, providing enhanced stability, mucoadhesive properties, and improved bioavailability of the pyrazolone derivative for treating Alzheimer's disease.
[0056] The method 200 may include encapsulating a pyrazolone derivative within liposomes using a solvent evaporation technique, wherein the liposomes are configured to enhance the stability and bioavailability of the pyrazolone derivative. The method 200 may also include incorporating phospholipids selected from the group consisting of phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine into the liposome structure, wherein the phospholipids contribute to the structural integrity of the liposomal formulation and facilitate the encapsulation process. The method 200 may also include adding cholesterol to the liposomal mixture, wherein the cholesterol modulates the fluidity and permeability of the liposomal membrane, ensuring a controlled and sustained release of the pyrazolone derivative. The method 200 may also include including chitosan as a stabilizing agent in the liposomal formulation, wherein the chitosan enhances the mucoadhesive properties of the liposomes. The method 200 may also include attaching a targeting moiety selected from the group consisting of antibodies, peptides, or small molecules to the surface of the liposome, wherein the targeting moiety facilitates the targeted delivery of the pyrazolone derivative to neuronal cells.
[0057] At 102, liposomal encapsulation of pyrazolone derivative.
[0058] At 104, phospholipids derived from natural sources form the structural integrity of the liposome.
[0059] At 106, cholesterol incorporated to modulate the membrane fluidity and controlled release of the active ingredient.
[0060] At 108, chitosan used as a stabilizing agent.
[0061] At 110, targeting moiety attached to the liposome for specific delivery to neuronal cells.
[0062] At 112, optimization of liposome size for effective penetration across the blood-brain barrier.
[0063] At 114, a precise ratio of cholesterol and phospholipids to maintain the liposome's structural integrity and functionality.
[0064] FIG. 2 illustrates a flowchart of a method for treating Alzheimer's disease using liposomal pyrazolone derivative, in accordance with an exemplary embodiment of the present disclosure.
[0065] At 202, encapsulating a pyrazolone derivative within liposomes using a solvent evaporation technique, wherein the liposomes are configured to enhance the stability and bioavailability of the pyrazolone derivative.
[0066] At 204, incorporating phospholipids selected from the group consisting of phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine into the liposome structure, wherein the phospholipids contribute to the structural integrity of the liposomal formulation and facilitate the encapsulation process.
[0067] At 206, adding cholesterol to the liposomal mixture, wherein cholesterol modulates the fluidity and permeability of the liposomal membrane, ensuring a controlled and sustained release of the pyrazolone derivative.
[0068] At 208, including chitosan as a stabilizing agent in the liposomal formulation, wherein the chitosan enhances the mucoadhesive properties of the liposomes.
[0069] At 210, attaching a targeting moiety selected from the group consisting of antibodies, peptides, or small molecules to the surface of the liposome, wherein the targeting moiety facilitates the targeted delivery of the pyrazolone derivative to neuronal cells.
[0070] FIG. 3 illustrates a step-by-step of the working model of a formulation and method for treating Alzheimer's disease using liposomal pyrazolone derivative, in accordance with an exemplary embodiment of the present disclosure.
[0071] At 302, In-silico screening of a series of compounds and performing molecular docking. A review of literature was done to identify the disease and drug genes. Common genes were identified by using Venny 2.0 which were later used for constructing a network on Cytoscape. Later, the docking studies were carried out for the same by using Schrödinger software.
[0072] At 304, synthesis & characterization of the compound. Synthesis of the compound was carried out by using modified Revana Sidhhapa's method. Characterization was performed by NMR, FT-IR and LC-MS.
[0073] At 306, preparation of nanoformulation & characterization. Establishment of the standard calibration curve was done and different concentrations of the lipid, cholesterol were checked for their solubility levels. Optimization was done by preparing four nanoformulations at minimum and maximum concentrations. The best one nanoformulation was selected on the basis of drug release and entrapment efficiency
[0074] At 308, Evaluation of anti-Alzheimer's activity by in vitro and in vivo assays. Pure drug, nanoformulation and standard drug were used to perform different behavioural studies. The brain was homogenized and used for determination of AChE and different antioxidant enzymes. The results revealed good retention memory and percentage alteration in EPM and Y maze respectively. The compound was also found to increase the activity of antioxidant enzymes and decrease the activity of AChE enzyme.
[0075] While the invention has been described in connection with what is presently considered to be the most practical and various embodiments, it will be understood that the invention is not to be limited to the disclosed embodiments, but on the contrary, is intended to cover various modifications and equivalent arrangements included within the scope of the appended claims.
[0076] A person of ordinary skill in the art may be aware that, in combination with the examples described in the embodiments disclosed in this specification, units and algorithm steps may be implemented by electronic hardware, computer software, or a combination thereof.
[0077] The foregoing descriptions of specific embodiments of the present disclosure have been presented for the purposes of illustration and description. They are not intended to be exhaustive or to limit the present disclosure to the precise forms disclosed, and many modifications and variations are possible in light of the above teaching. The embodiments were chosen and described to best explain the principles of the present disclosure and its practical applications, and to thereby enable others skilled in the art to best utilize the present disclosure and various embodiments with various modifications as are suited to the particular use contemplated. It is understood that various omissions and substitutions of equivalents are contemplated as circumstances may suggest or render expedient, but such omissions and substitutions are intended to cover the application or implementation without departing from the scope of the present disclosure.
[0078] Disjunctive language such as the phrase "at least one of X, Y, Z," unless specifically stated otherwise, is otherwise understood with the context as used in general to present that an item, term, etc., may be either X, Y, or Z, or any combination thereof (e.g., X, Y, and/or Z). Thus, such disjunctive language is not generally intended to, and should not, imply that certain embodiments require at least one of X, at least one of Y, or at least one of Z to each be present.
[0079] In a case that no conflict occurs, the embodiments in the present disclosure and the features in the embodiments may be mutually combined. The foregoing descriptions are merely specific implementations of the present disclosure, but are not intended to limit the protection scope of the present disclosure. Any variation or replacement readily figured out by a person skilled in the art within the technical scope disclosed in the present disclosure shall fall within the protection scope of the present disclosure. Therefore, the protection scope of the present disclosure shall be subject to the protection scope of the claims.
, Claims:I/We Claim:
1. A formulation for treating Alzheimer's disease using liposomal pyrazolone derivative (100) comprising:
a liposomal encapsulation of the pyrazolone derivative, wherein the liposome is configured to enhance the stability and bioavailability of the pyrazolone derivative;
phospholipids selected from the group consisting of phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine, wherein the phospholipids contribute to the structural integrity of the liposomal formulation and facilitate the encapsulation process;
cholesterol, wherein the cholesterol is incorporated to modulate the fluidity and permeability of the liposomal membrane, ensuring the controlled release of the pyrazolone derivative;
chitosan, wherein the chitosan is used as a stabilizing agent to enhance the mucoadhesive properties of the liposomal formulation;
a targeting moiety selected from the group consisting of antibodies, peptides, or small molecules, wherein the targeting moiety is attached to the surface of the liposome to facilitate the targeted delivery of the pyrazolone derivative to neuronal cells.
2. The formulation (100) as claimed in claim 1, wherein the pyrazolone derivative is selected from the group consisting of antipyrine, aminopyrine, dipyrone, or any combination thereof.
3. The formulation (100) as claimed in claim 1, wherein the phospholipids are derived from natural sources such as soy lecithin or egg yolk, enhancing the biocompatibility of the liposomal formulation.
4. The formulation (100) as claimed in claim 1, wherein the liposome has a size range between 50 to 200 nanometres, optimizing the penetration across the blood-brain barrier.
5. The formulation (100) as claimed in claim 1, wherein the targeting moiety is conjugated to the liposome at a ratio of 1-5 molecules of the targeting agent per liposome, ensuring optimal targeting efficiency and specificity in delivering the pyrazolone derivative to neuronal cells.
6. The formulation (100) as claimed in claim 1, wherein the cholesterol to phospholipid ratio is between 1:1 and 1:2, providing an optimal balance between membrane fluidity and rigidity.
7. The formulation (100) as claimed in claim 1, wherein the phospholipids constitute 40-60% of the total lipid content in the liposomal formulation, optimizing the structural integrity and encapsulation efficiency of the pyrazolone derivative.
8. The formulation (100) claimed in claim 1, wherein the cholesterol is present at a concentration of 10-20% of the total lipid content, which is specifically calibrated to modulate the membrane fluidity and permeability, ensuring controlled and sustained release of the pyrazolone derivative.
9. The formulation (100) as claimed in claim 1, wherein the chitosan is included at a concentration of 0.5-5% of the total formulation weight, providing enhanced stability, mucoadhesive properties, and improved bioavailability of the pyrazolone derivative for treating Alzheimer's disease.
10. A method for treating Alzheimer's disease using liposomal pyrazolone derivative (200) comprising:
encapsulating a pyrazolone derivative within liposomes using a solvent evaporation technique, wherein the liposomes are configured to enhance the stability and bioavailability of the pyrazolone derivative;
incorporating phospholipids selected from the group consisting of phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine into the liposome structure, wherein the phospholipids contribute to the structural integrity of the liposomal formulation and facilitate the encapsulation process;
adding cholesterol to the liposomal mixture, wherein the cholesterol modulates the fluidity and permeability of the liposomal membrane, ensuring a controlled and sustained release of the pyrazolone derivative;
including chitosan as a stabilizing agent in the liposomal formulation, wherein the chitosan enhances the mucoadhesive properties of the liposomes;
attaching a targeting moiety selected from the group consisting of antibodies, peptides, or small molecules to the surface of the liposome, wherein the targeting moiety facilitates the targeted delivery of the pyrazolone derivative to neuronal cells.

Documents