VEHICLE ENCAPSULATED SPECIALIZED PRO-RESOLUTION MEDIATORS (SPMs), METHODS AND APPLICATIONS THEREOF

Abstract

The present disclosure provides vehicle encapsulated Specialized Pro-resolution Mediator (SPM). More particularly, provided herein is vehicle encapsulated RvD1. Said encapsulation is preferably achieved through liposomes. Said vehicle encapsulated SPMs of the present disclosure find application in the prevention, prophylaxis, treatment and / or management of joint related diseases such as osteoarthritis (OA). Further provided in the present disclosure are methods of preparation and application of the vehicle encapsulated SPMs. Encapsulation of SPMs allows the SPMs to exert their function while also ensuring sustained release and longer retention of the SPM at the target site.

Description

TECHNICAL FIELDThe present disclosure relates to the fields of disease management, pharmaceuticals andformulations. Particularly, the present disclosure provides vehicle encapsulated SpecializedPro-resolution Mediators (SPMs). More particularly, provided herein is vehicle encapsulatedRvD1. Said vehicle encapsulated SPMs of the present disclosure find application in theprophylaxis and / or treatment of joint related diseases such as osteoarthritis (OA). Furtherprovided in the present disclosure are methods of preparation and application of the vehicleencapsulated SPMs.BACKGROUND OF THE DISCLOSUREOsteoarthritis (OA) is the most common joint pathology. According to recent estimates, 303.1million patients were suffering from Osteoarthritis (OA) in 2020 worldwide. OA ischaracterized by progressive loss of cartilage, pain, damage to the subchondral bone, andeventual loss of function of the affected joint in humans. Current treatment includesadministering glucosamine, glucocorticoids, and other NSAIDS. These treatments often fail toarrest the progressing cartilage deterioration and have several other drawbacks like gastricbleeding and increased propensity to osteoporosis in women. Most OA patients eventuallyrequire highly invasive and expensive joint-replacement surgery. Other strategies, likeviscosupplementation and oral glucosamine administration, have achieved inconclusive resultsin humans. Despite the widespread prevalence of the disease, there are no approved disease-modifyingOA drugs for human use. Due to the lack of a reliable disease-modifying OA drug,tremendous loss of quality of life and revenue goes unchecked annually.Factors like old age, diet, obesity, and trauma contribute to inflammation in humans. Cellularchanges include decreased chondrocyte viability and increased proliferation, altered matrixsynthesis, and increased levels of pro-inflammatory cytokines such as interleukin-1β (IL-1β)and tumor necrosis factor (TNF)-α, resulting in elevated production of matrix degradingenzymes and reactive oxygen species. Chronic, low-grade inflammation is a significant driverof OA and is reflected in the surge in the levels of pro-inflammatory cytokines in the synovialfluid and systemic circulation.Current treatments for the disease rely on symptomatic relief. Targeting chronic low-gradeinflammation is one of the viable strategies for treating this disease. Specialized pro-resolutionmediators (SPMs) are powerful agents of resolution but are challenging to deliver because oftheir short half-life. Blockade of inflammation by inhibiting the action of inflammatorycytokines like IL-1β and TNF-α is considered a viable treatment strategy for OA. However,such approaches have proved sub-therapeutic in human clinical trials. This failure is attributedto the efficient lymphatic drainage that rapidly clears (1-5 h) off the therapeutic molecules fromthe joint. Some therapeutics like Tanezumab (antibody against nerve growth factor (NGF))reduce pain in the short term but fail to cease damage to the cartilage.Since small molecule drugs diffuse rapidly out of the joint, intraarticular delivery of small drugshas not been successful to treat joint-related diseases. The need of the hour is therefore aneffective drug or active agent for the treatment of OA.SUMMARY OF THE DISCLOSUREAddressing the above identified need in the art for an active agent for facilitating successfulintraarticular delivery of small drugs for treatment or management of joint-related diseases,provided herein is a liposome encapsulated specialized pro-resolution mediator (SPM),wherein the liposome has size ranging from about 100nm to about 5μm.In some embodiments, the liposome is formed by ampiphilic lipids.In some embodiments, the liposome is formed by lipids selected from a group comprising 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), Egg Phosphatidylcholine (Egg PC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-distearoyl-sn-glycero-3-phosphocholine(DSPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), methoxy-poly(ethyleneglycol)2000-distearoylphosphatidylethanolamine (DSPE-PEG2000), or anycombination thereof.In some embodiments, the lipid(s) forming the liposome further comprises sterol(s). In someembodiments, the sterol is selected from a group comprising cholesterol, beta-Sitosterol,phytosterol and 20-alpha-Hydroxycholesterol or any combination thereof. In an exemplaryembodiment, the sterol is cholesterol.In some embodiments, the liposome is formed by about 40% to about 94% by mole of DPPC;about 1% to about 50% of DSPE-PEG2000; and, optionally about 0% to about 30% of sterolby mole. In some embodiments, the liposome is formed by 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), methoxy-poly(ethyleneglycol)2000-distearoylphosphatidyletholamine (DSPE-PEG2000), and sterol at a ratio of about 85:5:10 bymole.In some embodiments, the SPM is a resolving family molecule selected from a groupcomprising Resolvin D1 (RvD1), aspirin-triggered Resolvin D1 and Resolvin E1 or anycombination thereof.In some embodiments, the liposome has size ranging from about 150nm to about 1μm.In some embodiments, the liposome has size ranging from about 151nm to about 900nm.In an exemplary embodiment, the liposome has size ranging from about 300nm to about 500nm.In some embodiments, the liposome encapsulated SPM comprises SPM at a concentrationranging from about 15 ng / mg of liposomes to about 1200 ng / mg of liposomes.Further provided herein is a method of obtaining SPM loaded liposome comprising -a) Hydration of thin film(s) of liposome forming lipid(s) with solvent(s) to generatevesicles;b) Extrusion of the vesicles through a filter to generate liposomes; andc) Pelleting and re-suspending the liposomes in SPM containing solutionto obtain the SPM loaded liposome.In some embodiments, the method further comprises washing of the obtained SPM-loadedliposomes to remove excess unloaded SPM from the extra-liposomal environment.In some embodiments, the liposome forming lipid(s) is selected from a group comprising 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), Egg Phosphatidylcholine (Egg PC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-distearoyl-sn-glycero-3-phosphocholine(DSPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), methoxypoly(ethyleneglycol)2000-distearoylphosphatidylethanolamine (DSPE-PEG2000), or anycombination thereof; and optionally, comprises sterol(s).In some embodiments, the solvent employed for hydration of the lipid film is selected fromsolvents such as but not limited to calcium acetate, barium acetate, and magnesium acetate orany combination thereof.In some embodiments, the extrusion is performed through filters having pore size ranging fromabout 100 nm to about 5μm.In a preferred embodiment, the extrusion is performed through filters having pore size rangingfrom about 150 nm to about 1μm.In some embodiments, the extrusion is performed through filters having pore size ranging fromabout 150 nm to about 900nm.In an exemplary embodiment, the extrusion is performed through filters having pore sizeranging from about 300 nm to about 500 nm.In some embodiments, the SPM is a resolving family molecule selected from a groupcomprising Resolvin D1 (RvD1), aspirin-triggered Resolvin D1 and Resolvin E1 or anycombination thereof.In some embodiments, the SPM containing solution comprises solvent(s) selected from a groupcomprising sodium sulfate, lithium sulfate, and potassium sulfate acetate or any combinationthereof. In some embodiments, the SPM containing solution comprises about 50ng SPM / mLsolvent to about 4000ng SPM / mL solvent.In some embodiments, the solvent employed for hydration has a pH ranging from about 5 toabout 7, preferably about 6; and wherein the SPM containing solution has a pH ranging fromabout 2 to about 4.5, preferably about 4.In some embodiments, the pelleting and re-suspension of the liposomes in SPM containingsolution is at a temperature of about 37°C to about 60°C for about 0.5 hours to about 2 hours.In some embodiments, the washing is performed with a solvent selected from a groupcomprising Phosphate Buffered Saline (PBS), Normal Saline (NS), and Hank's Balanced SaltSolution (HBSS) or any combination thereof.In some embodiments, the obtained SPM loaded liposome has size ranging from about 150nmto about 1μm.In some embodiments, the method has encapsulation efficiency of about 10% to about 100%,preferably about 43% to about 99%.In some embodiments, provided herein is a composition comprising the liposome encapsulatedSPM of the present disclosure and one or more pharmaceutically acceptable excipients oradditives.In some embodiments, the composition is a sustained release formulation.In some embodiments, the composition is formulated into an injectable formulation.Further provided in the present disclosure is use of the liposome encapsulated SPM of thepresent disclosure or the composition comprising the liposome encapsulated SPM for theprophylaxis, prevention, management and / or therapeutic treatment of joint related diseases.In some embodiments, the use of the liposome encapsulated SPM allows sustained release forabout 1 day to about 15 days.In an exemplary embodiment, the use of the liposome encapsulated SPM allows sustainedrelease for about 9 days to about 15 days.In another embodiment, provided herein is a method of preventing or treating joint relateddiseases comprising administering the liposome encapsulated SPM of the present disclosure orthe composition comprising the liposome encapsulated SPM to a subject in need thereof.In some embodiments, the administration is by way of injection, preferably an intraarticularinjection. In some embodiments, the method reduces joint damage by about 4 fold to about 10fold as compared to an untreated subject.In some embodiments, provided herein is a kit comprising one or more of the liposomeencapsulated SPM of the present disclosure or the composition comprising the liposomeencapsulated SPM, one or more syringes for administration of the liposome encapsulated SPMand optionally, an instruction manual for enabling use of the kit or any combination thereof.The present disclosure further provides a pre-filled pen or syringe comprising the liposomeencapsulated SPM of the present disclosure or the composition comprising the liposomeencapsulated SPM.BRIEF DESCRIPTION OF THE ACCOMPANYING FIGURESIn order that the disclosure may be readily understood and put into practical effect, referencewill now be made to exemplary embodiments as illustrated with reference to the accompanyingfigures. The figures together with detailed description below, are incorporated in and form partof the specification, and serve to further illustrate the embodiments and explain variousprinciples and advantages, where:Figure 1 depicts characterization and release profile of lipo-RvD1. (A) The size distribution ofliposomes as measured using dynamic light scattering. (B) Cryo-TEM micrographs of lipo-RvD1. (C) Size stability of liposomes in phosphate buffered saline (PBS) as measured by DLS;n=3. Data is represented as mean ± SD.Figure 2 depicts quantification and encapsulation of lipo-RvD1. (A) Plot of the area under thecorresponding peak on the chromatogram (area under the curve; AUC) against concentrationof RvD1 injected. n= 2 replicates for each concentration. (B) Plot depicting RvD1 loaded as afunction of initial gradient provided across the lipid bilayer of the liposomes; n=3-4.****p<0.0001 versus loading with 50 ng / mg of RvD1 using ANOVA followed by Tukey'sposthoc test. (C) Loading of RvD1 into liposomes containing different cholesterolconcentrations; n=3 for each liposome test group. Groups were tested for statisticalsignificance using ANOVA followed by Tukey's posthoc test. Data is represented as mean ±SD.Figure 3 depicts stable encapsulation of RvD1. (A) Retention profile of RvD1 in liposomescontaining different cholesterol concentrations; n=2-3 replicates per time point in every group.(B) Quantification of in vitro release of RvD1 from lipo-RvD1 when incubated at 37°C at pH7.4; n=3. Data were represented as mean ± SD.Figure 4 depicts intraarticular retention studies (A) Fluorescence images of live mice depictingthe difference between intraarticular retention of fluorescent liposomes and free dye at day 0and day 1. (B) Quantification of retention of IA-injected fluorescent liposomes and free dyefrom the respective joint; n= 4-5 IA injected knee joints per group. **p<0.01 between %fluorescence of free drug and % fluorescence of liposomes using Analysis of Variance(ANOVA) followed by Tukey's posthoc test. (C) Quantification of IA clearance of differentsizes of liposomes as measured by Bruker XTreme II; n=4 injected knee joints per group forevery time point. *p <0.05 between respective data from mice joints injected with 350 nm and900 nm liposomes using ANOVA followed by Tukey's posthoc test. #p <0.05 betweenrespective data from mice joints injected with 150 nm and 900 nm liposomes using ANOVAfollowed by Tukey's posthoc test. Data represented as mean±SEM.Figure 5 depicts alleviation of cartilage damage upon prophylactic administration of lipo-RvD1. (A) Timeline of the experiment and dosage regime. (B) Plot of weights of animals withrespect to time; n=4-6 mice per group for every time point. (C) Characteristic Safranin-Ostainedhistology sections of different groups of mice (scale bar 200 μm). (D) OARSI scoresof Safranin O-stained sections of mice knee joints administered with respective treatment; n=5-7 per group. *p=0.0256 between OARSI scores of sections obtained from untreated and lipo-RvD1 treated knee joints using Kruskal-Wallis test for non-parametric datasets followed byDunn's posthoc test. For D, after screening all groups for outliers with the Grubbs test, onepoint in the lipo-RvD1 treated group proved outlier and was subsequently removed from furtheranalysis. All values are expressed as mean ± SD.Figure 6 depicts increase in the proportion of M2 macrophages over M1 macrophages in thesynovial membrane upon prophylactic administration of lipo-RvD1. (A) IHC images depictinglevels of iNOS+ M1 macrophages synovial membrane (scale bar 50 μm). (B) Quantification ofiNOS+ M1 macrophages in the synovial membrane; n=4-6 animals per group. (C) IHC imagesdepicting levels of CD206+ M2 macrophages in synovial membrane (scale bar 50 μm). (D)Quantification of CD206+ M2 macrophages in the synovial membrane; n=4-6 per group.*p=0.0153 between the levels of CD206+ cells in synovium obtained from untreated and lipo-RvD1 treated knee joints using ANOVA followed by Tukey's posthoc test. (E) The ratio ofM1 / M2 cells in the synovial membrane; n=4-6 animals per group. ****p<0.0001 between theratios of M1 / M2 cells in synovium obtained from untreated and lipo-RvD1 treated knee jointsusing ANOVA followed by Tukey's posthoc test. All values are expressed as mean ± SD.Figure 7 depicts inhibition of activity of catabolic mediators upon prophylactic administrationof lipo-RvD1. Representative IHC images of (A) matrix metalloproteinase 13 (MMP13), (B)A disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS5).Figure 8 depicts protection of cartilage from progressing damage upon therapeuticadministration of lipo-RvD1. (A) Timeline for the study and dosage regime. (B) Safranin-Ostainedcharacteristic histological images of different groups of animals (scale bar 200 μm).(C) OARSI scores of Safranin O-stained sections of mice joints administered with respectivetreatment; n=5-7 per group. **p=0.0058 between OARSI scores of sections obtained fromuntreated and lipo-RvD1 treated knee joints using Kruskal-Wallis test for non-parametricdatasets followed by Dunn's posthoc test. Values are expressed as mean ± SD.Figure 9 depicts increase in the proportion of M2 macrophages over M1 macrophages in thesynovial membrane upon therapeutic administration of Lipo-RvD1. (A) Characteristic IHCimages depicting levels of iNOS+ M1 macrophages in the synovial membrane of respectivemice joints (scale bar 50 μm). (B) Quantification of iNOS+ M1 macrophages in the synovialmembrane of respective mice joints; n=4-6 animals per group. **p=0.0070 between the levelsof iNOS+ cells in synovium obtained from untreated and lipo-RvD1 treated knee joints usingANOVA followed by Tukey's posthoc test. (C) IHC images depicting levels of CD206+ M2macrophages in synovial membrane (scale bar 50 μm). (D) Quantification of CD206+ M2macrophages in the synovial membrane; n=4-6 per group. *p=0.0185 between the levels ofcells in synovium obtained from untreated and lipo-RvD1 treated knee joints ANOVAfollowed by Tukey's posthoc test. (E) The ratio of M1 / M2 cells in the synovial membranes ofknee joints administered with respective injections; n=4-6 animals per group. For C, afterscreening all groups for outliers with the Grubbs test, one point in the DMM group provedoutlier and was subsequently removed from further analysis.Figure 10 depicts inhibition of the activity of catabolic mediators in OA joints by therapeuticadministration of lipo-RvD1. Representative IHC images of (A) matrix metalloproteinase 13(MMP13), (B) A disintegrin and metalloproteinase with thrombospondin motifs-5(ADAMTS5).Figure 11 depicts reduction of osteophytes and OA-associated pain by Lipo-RvD1. (A)Characteristic microCT images of mice knee joints administered with respective treatments.Quantification of (B) trabecular spacing, (C) trabecular thickness, and (D) fraction bonevolume (bone volume / total volume) for different treatment groups. For C, **p=0.008 betweendata from untreated and lipo-RvD1 treated animals using unpaired t-test. For D, *p =0.04between respective data from untreated and lipo-RvD1 treated animals using ANOVAfollowed by Tukey's posthoc test; n=3-4 joints per group. (E) Paw-withdrawal response ofdifferent treatment groups as measured by von Frey filaments. **p=0.0023 between respectivedata from the untreated and lipo-RvD1 treated using Mann-Whitney U-test. Values areexpressed as mean ± SD.Figure 12 depicts release profile of lipo-RvD1 in synovial fluid obtained from OA patients.Figure 13 depicts (a) weight profiles of mice fed high-fat diet (HFD) and normal diet (ND).Serum levels of (b) cholesterol, (c) LDL, and the serum ratios (d) TC / HDL-c and (e) LDLc / HDL-c; n=8 lean animals and n=12 obese animals (f) Characteristic safranin-O stainedsections of cartilage (scale bar 50 μm). (g) OARSI scores indicating the severity of the jointdamage; n=4-8 animals per group. For a, b, c, d, e, and g, *p<0.05, **p<0.01, and ***p<0.001between the respective groups indicated in the figures using ANOVA followed by Tukey'sposthoc test. Values are expressed as mean ± SD. Scale bar 50 μm.Figure 14 depicts effect of prophylactic administration of lipo-RvD1 on ObOA mouse model(a) Timeline of the experiment. (b) Characteristic Safranin-O-stained histology sections ofdifferent groups of mice (scale bar 200 μm). (c) OARSI scores of Safranin O-stained sectionsof mice knee joints administered with respective treatment; n=7 joints injected with free RvD1,n=7 DMM joints, n=7 sham joints, and n=7 joints injected with lipo-RvD1. (d) IHC imagesdepicting levels of iNOS+ M1 macrophages synovial membrane (scale bar 50 μm). (e)Quantification of iNOS+ M1 macrophages in the synovial membrane; n=7 DMM joints, n=8joints treated with free RvD1, n=8 sham joints, and n=8 joints treated with lipo-RvD1. (f) IHCimages depicting levels of CD206+ M2 macrophages in synovial membrane (scale bar 50 μm).(g) Quantification of CD206+ M2 macrophages in the synovial membrane; n=7 joints treatedwith free RvD1, n=7 DMM joints, n=7 sham joints, and n= 8 joints treated with lipo-RvD1.For c and g one point in the lipo-RvD1 group was removed after outlier analysis (Grubbs test).For c, e and g *p<0.05, ***p<0.001, and ****p<0.0001 between the respective groupsindicated in the figures using ANOVA followed by Tukey's posthoc test for parametric datasetsor Kruskal-Wallis test followed by Dunn's posthoc test for nonparametric datasets. Values areexpressed as mean ± SD. Scale bar 50 μm.Figure 15 depicts effect of blank liposomes on joint pathology.Figure 16 depicts immunohistochemical images of sections stained for expression of thecatabolic markers in the ObOA group subjected to prophylactic administration of rvD1,(a)ADAMTS5 and (b)MMP13. Scale bar 50 μm.Figure 17 depicts effect of therapeutic administration of lipo-RvD1 in ObOA mouse model.(a) Timeline for the study. (b) Safranin-O-stained characteristic histological images of differentgroups of animals (scale bar 200 μm). (c) OARSI scores of Safranin O-stained sections of micejoints administered with respective treatment; n=6 DMM joints, n=7 joints treated with freeRvD1, n=7 sham joints, and n=7 joints treated with lipo-RvD1. (d) Characteristic IHC imagesdepicting levels of iNOS+ M1 macrophages in the synovial membrane of respective mice joints(scale bar 50 μm). (e) Quantification of iNOS+ M1 macrophages in the synovial membrane ofrespective mice joints; n=6 DMM joints, n=8 joints treated with lipo-RvD1 and sham joint, andn=6 joints treated with free RvD1. (f) IHC images depicting levels of CD206+ M2macrophages in synovial membrane (scale bar 50 μm). (g) Quantification of CD206+ M2macrophages in the synovial membrane; n=6 joints treated with free RvD1, n=6 DMM joints,n=8 sham joints, n=7 joints treated with free RvD1, and n=8 joints treated with lipo-RvD1. Forc , one point in the lipo-RvD1 group was removed after outlier analysis (Grubbs test). For c, e,and g, *p<0.05, **p<0.01, and ****p<0.0001 between the respective groups indicated in thefigures using ANOVA followed by Tukey's posthoc test for parametric datasets or Kruskal-Wallis test followed by Dunn's posthoc test for nonparametric datasets. Values are expressedas mean ± SD. Scale bar 50 μm.Figure 18 depicts Immunohistochemical images of sections stained for expression of thecatabolic markers in the ObOA group subjected to therapeutic administration of rvD1,(a)ADAMTS5 and (b)MMP13. Scale bar 50 μm.Figure 19 depicts Immunohistochemical images of sections stained for expression of β-cateninwhen lipo-RvD1 was administered (a)prophylactically and (b)therapeutically. Scale bar 50 μm.Figure 20 depicts Lipo-RvD1 treated mice show reduced synovitis. (a) Images of stainedsections of synovial membranes of joints treated with lipo-RvD1 prophylactically. (b)Thickness of the synovial membrane of joints treated with lipo-RvD1 prophylactically; n=5-8animals per group. (c) Images of stained sections of synovial membranes of joints treated withlipo-RvD1 therapeutically. (d)Thickness of the synovial membrane of joints treated with lipo-RvD1 therapeutically; n=5-8 animals per group. (e) Magnified images of stained sections ofsynovial membranes of joints treated with lipo-RvD1 prophylactically. (f) Quantification ofcells in the synovial membrane of joints treated with lipo-RvD1 prophylactically. (g) Magnifiedimages of stained sections of synovial membranes of joints treated with lipo-RvD1therapeutically. (h) Quantification of cells in the synovial membrane of joints treated with lipo-RvD1 therapeutically. For b, d, f, h, *p<0.05, **p<0.01, and ***p<0.0001 between therespective groups indicated in the figures using ANOVA followed by Tukey's posthoc test.Values are expressed as mean ± SD. Scale bar 50 μm.Figure 21 depicts analgesic effect of Lipo-RvD1 in (a) prophylactic and (b) therapeuticregimen; n=6-8 mice per group in both studies. For a and b, *p<0.05 and, **p<0.01,***p<0.001, and ****p<0.0001 between the respective groups indicated in the figures usingANOVA followed by Tukey's posthoc test. Values are expressed as mean ± SD. Scale bar 50μm.DETAILED DESCRIPTION OF THE INVENTIONGeneral definitionsAs used herein, the abbreviation 'RvD1' has been used in reference to the molecule 'ResolvinD1'. Reference to RvD1 in the present disclosure encompasses in scope structural andfunctional analogs of RvD1.The abbreviation 'OA' has been used in reference to Osteoarthritis. The abbreviation 'IA' hasbeen used while referring to 'intraarticular' injection or retention, to specify localadministration or retention of a drug formulation.'SPM' has been used as an abbreviation while referring to 'Specialized Pro-resolutionMediators'. The terms 'lipo-SPM', 'liposome encapsulated SPM' and 'SPM loaded liposome'have been used interchangeably throughout the present disclosure while referring to SPMencapsulated in liposomes. Similarly, the terms 'lipo-RvD1', 'liposome encapsulated RvD1'and 'RvD1 loaded liposome' have been used interchangeably throughout the present disclosurewhile referring to RvD1 encapsulated in liposomes.As used herein, the term 'active loading' or obvious variants thereof as used throughout thepresent disclosure to define the refers to the strategy employed in the present disclosure to loadSPMs into liposomes by employing a differential pH gradient across the lipid bilayer to drivethe SPM molecule into the intraliposomal space.As used herein, the term 'encapsulation efficiency' refers to the ratio of amount of drugcaptured into vehicles like liposomes to the total amount drug added during the respectiveloading.As used herein, the term 'subject' is a vertebrate, such as a mammal, such as a human.Mammals include, but are not limited to, humans, livestock, athletic animals, pets and the like.As used herein, the term 'sustained release' refers to delivery of a specific drug such as SPMin the present disclosure for a prolonged period of time.As used herein, the term 'comprising' when placed before the recitation of steps in a methodmeans that the method encompasses one or more steps that are additional to those expresslyrecited, and that the additional one or more steps may be performed before, between, and / orafter the recited steps. For example, a method comprising steps a, b, and c encompasses amethod of steps a, b, x, and c, a method of steps a, b, c, and x, as well as a method of steps x,a, b, and c. Furthermore, the term "comprising" when placed before the recitation of steps in amethod does not (although it may) require sequential performance of the listed steps, unlessthe content clearly dictates otherwise. For example, a method comprising steps a, b, and cencompasses, for example, a method of performing steps in the order of steps a, c, and b, theorder of steps c, b, and a, and the order of steps c, a, and b, etc.With respect to the use of substantially any plural and / or singular terms herein, those havingskill in the art can translate from the plural to the singular and / or from the singular to the pluralas is appropriate to the context and / or application. The various singular / plural permutationsmay be expressly set forth herein for sake of clarity. The suffix '(s)' at the end of any term inthe present disclosure envisages in scope both the singular and plural forms of said term.As used in this specification and the appended claims, the singular forms 'a', 'an' and 'the'includes both singular and plural references unless the content clearly dictates otherwise. Theuse of the expression 'at least' or 'at least one' suggests the use of one or more elements oringredients or quantities, as the use may be in the embodiment of the disclosure to achieve oneor more of the desired objects or results. As such, the terms 'a' (or 'an'), 'one or more', and 'atleast one' can be used interchangeably herein.Numerical ranges stated in the form 'from x to y' include the values mentioned and those valuesthat lie within the range of the respective measurement accuracy as known to the skilled person.If several preferred numerical ranges are stated in this form, of course, all the ranges formedby a combination of the different end points are also included.The terms 'about' or 'approximately' as used herein when referring to a measurable value suchas a parameter, an amount, a temporal duration, and the like, are meant to encompass variationsof and from the specified value, such as variations of + / -10% or less, + / -5% or less, + / -1% orless, and + / -0.1% or less of and from the specified value, insofar such variations are appropriateto perform in the disclosed invention. It is to be understood that the value to which the modifier'about' or 'approximately' refers is itself also specifically, and preferably, disclosed.As used herein, the terms 'include', 'have', 'comprise', 'contain' etc. or any form said termssuch as 'having', 'including', 'containing', 'comprising' or 'comprises' are inclusive and willbe understood to imply the inclusion of a stated element, integer or step, or group of elements,integers or steps, but not the exclusion of any other element, integer or step, or group ofelements, integers or steps.As regards the embodiments characterized in this specification, it is intended that eachembodiment be read independently as well as in combination with another embodiment. Forexample, in case of an embodiment 1 reciting 3 alternatives A, B and C, an embodiment 2reciting 3 alternatives D, E and F and an embodiment 3 reciting 3 alternatives G, H and I, it isto be understood that the specification unambiguously discloses embodiments correspondingto combinations A, D, G; A, D, H; A, D, I; A, E, G; A, E, H; A, E, I; A, F, G; A, F, H; A, F, I;B, D, G; B, D, H; B, D, I; B, E, G; B, E, H; B, E, I; B, F, G; B, F, H; B, F, I; C, D, G; C, D, H;C, D, I; C, E, G; C, E, H; C, E, I; C, F, G; C, F, H; C, F, I, unless specifically mentionedotherwise.DisclosureAddressing the need in the art for effective means to treat joint-related diseases, the presentdisclosure provides vehicle encapsulated specialized pro-resolution mediators (SPMs). Saidvehicle encapsulated SPMs of the present disclosure are stable, non-toxic and are retained forlonger durations in the joints compared to free SPMs, thus generating a high local drug (SPM)concentration.In some embodiments, the SPM is selected from a group comprising molecules from Resolvinfamilies such as but not limited to Resolvin D1 (RvD1), aspirin-triggered Resolvin D1 andResolvin E1.In some embodiments, the encapsulation in carriers is achieved by employment of lipid-baseddelivery systems such as but not limited to liposomes. Said liposomes, in non-limitingembodiments, are synthetic liposomes.In some embodiments, provided herein is a liposome encapsulated SPM. In a non-limitingembodiment, the present disclosure provides liposome encapsulated RvD1.In some embodiments, the encapsulation is nano-encapsulation. In some embodiments, the saidnano-encapsulation is facilitated through nano-liposomes. In exemplary embodiments of thepresent disclosure, the encapsulated SPM is nano-liposome encapsulated RvD1. Thus, thepresent disclosure, in some embodiments, provides nano-liposome encapsulated RvD1.Specialized pro-resolution mediators (SPMs) are powerful agents of resolution but arechallenging to deliver because of their short half-life. SPMs such as RvD1 polarizemacrophages to a pro-resolution M2 phenotype instead of the M1 phenotype. RvD1 is versatilein its activity, and mediates clearance of debris, reduces the influx of phagocytes, and promotesanabolism in chondrocytes. Exogenously administered RvD1 reduces the severity of jointrelateddiseases such as osteoarthritis, but the short half-life and limited in vivo retention ofsuch molecules limits the molecule's therapeutic potential.Said drawback with respect to local retention of the drug is addressed by encapsulation of RvD1in lipid-based drug delivery systems like liposomes. Liposomes act as efficient drug carriersbecause of their biodegradability, low toxicity, stability, flexible synthesis methods, and abilityto incorporate versatile cargo.In an exemplary embodiment, the present disclosure provides a liposome encapsulatedspecialized pro-resolution mediator (SPM), wherein the liposome has size ranging from about100nm to about 5μm.One of the objectives of the present disclosure is to facilitate efficient intraarticular delivery ofsmall drugs for the treatment or prophylaxis of OA and ensure their retention at the site ofdelivery. Without intending to be limited by theory, the liposome characterized by the abovedefined size allows maximization of intraarticular retention.In some embodiments, the liposome is formed by ampiphilic lipids.In some embodiments, the liposome is formed by lipids selected from a group comprising 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), Egg Phosphatidylcholine (Egg PC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-distearoyl-sn-glycero-3-phosphocholine(DSPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), methoxypoly(ethyleneglycol)2000-distearoylphosphatidylethanolamine (DSPE-PEG2000), or anycombination thereof.In some embodiments, the liposome is formed by lipids selected from a group comprising 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and methoxy-poly(ethyleneglycol)2000-distearoylphosphatidylethanolamine (DSPE-PEG2000) or a combination thereof.In some embodiments, the lipid(s) forming the liposome further comprises sterol(s).In some embodiments, the sterol is selected from but not limited to cholesterol, beta-Sitosterol,phytosterol and 20-alpha-Hydroxycholesterol or any combination thereof.In some embodiments, the sterol is cholesterol. Cholesterol molecules intercalate between thelong tails of other lipids and increase the fluidity and permeability of the lipid bilayer that formsthe liposomes.In exemplary embodiments, the liposome is formed by lipids selected from a group comprisingdipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and methoxy-poly(ethyleneglycol)2000-distearoylphosphatidylethanolamine (DSPE-PEG2000) or a combination thereof, optionallyalong with one or more sterol(s).In some embodiments, the liposome is formed by lipids selected from a group comprisingdipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and methoxy-poly(ethyleneglycol)2000-distearoylphosphatidylethanolamine (DSPE-PEG2000) or a combination thereof, optionallyalong with cholesterol.In some embodiments, the liposome is formed by lipids selected from a group consisting ofdipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and methoxy-poly(ethyleneglycol)2000-distearoylphosphatidylethanolamine (DSPE-PEG2000) or a combination thereof, optionallyalong with cholesterol.In some embodiments, the liposome is formed by any one or both lipids selected from a groupconsisting of dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and methoxypoly(ethyleneglycol)2000-distearoylphosphatidylethanolamine (DSPE-PEG2000), optionallyalong with cholesterol.In some embodiments, the liposome is formed by lipids selected from a group comprisingdipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and methoxy-poly(ethyleneglycol)2000-distearoylphosphatidylethanolamine (DSPE-PEG2000) or a combination thereof, along withcholesterol.In some embodiments, the liposome is formed by lipids selected from a group consisting ofdipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and methoxy-poly(ethyleneglycol)2000-distearoylphosphatidylethanolamine (DSPE-PEG2000) or a combination thereof, along withcholesterol.In some embodiments, the liposome is formed by any one or both lipids selected from a groupconsisting of dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and methoxypoly(ethyleneglycol)2000-distearoylphosphatidylethanolamine (DSPE-PEG2000), along withcholesterol.In some embodiments, the liposome is formed by dipalmitoyl-sn-glycero-3-phosphocholine(DPPC), methoxy-poly(ethyleneglycol)2000-distearoylphosphatidylethanolamine (DSPEPEG2000)and cholesterol.In some embodiments, the liposome comprises cholesterol at a concentration of about 0% toabout 30%.In some embodiments, the liposome comprises cholesterol at a concentration of 10% to about30%.In some embodiments, the liposome is formed by 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), methoxy-poly(ethyleneglycol)2000-distearoylphosphatidylethanolamine (DSPE-PEG2000), and cholesterol; wherein the liposomeis formed by about 40% to about 94% by mole of DPPC; about 1% to about 50% by mole ofDSPE-PEG2000.In an exemplary embodiment, the liposome is formed by 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), methoxy-poly(ethyleneglycol)2000-distearoylphosphatidylethanolamine (DSPE-PEG2000), and cholesterol at a ratio of about85:5:10 by mole.In some embodiments, the liposome has size ranging from about 150nm to about 1μm.Therefore, in some embodiments, the present disclosure provides a liposome encapsulatedspecialized pro-resolution mediator (SPM), wherein the liposome has size ranging from about150nm to about 1μm.In some embodiments, the liposome has size ranging from about 151nm to about 900nm.Therefore, in some embodiments, the present disclosure provides a liposome encapsulatedspecialized pro-resolution mediator (SPM), wherein the liposome has size ranging from about151nm to about 900nm.In an exemplary embodiment, the liposome has size ranging from about 300nm to about 500nm.Therefore, in some embodiments, the present disclosure provides a liposome encapsulatedspecialized pro-resolution mediator (SPM), wherein the liposome has size ranging from about300nm to about 500nm.Without intending to be limited by theory, while the intended objective of sustained retentionor release of SPM at the site of administration is achieved by employing liposomes having sizeranging from about 100nm to about 5μm, as shown through data in the working examples, atsizes below about 150nm and above about 1μm, there is a tendency of lower retention of theSPM at the site of administration. In some embodiments, it has been observed throughexperiments that the optimum retention of the SPM at the site of administration is achieved byemploying liposomes having size ranging from about 300 nm to about 500 nm. It will be wellunderstood, therefore, that the size of the liposomes employed for SPM encapsulation may bevaried depending on the intended span of retention, by lowering or increasing particle sizewithin the range of about 100nm to about 5μm.In some embodiments, the SPM loaded liposomes comprise SPM at a concentration rangingfrom about 15 ng / mg of liposomes to about 1200 ng / mg of liposomes.In exemplary embodiments, the SPM is RvD1 and the RvD1 loaded liposomes comprise RvD1at a concentration ranging from about 35.7±16.15 ng / mg of liposomes to about 1065±92 ng / mgof liposomes. Since RvD1 is extremely potent and exerts its function at pico- and nano-molarranges, lipo-RvD1 with lower loading of about 35.7±16.15 ng / mg of lipid also efficientlyachieves the desired results in terms of intraarticular retention of the drug and impedance ofjoint-related diseases such as but not limited to ortho-arthritis (OA).The SPM loaded, preferably RvD1 loaded liposomes of the present disclosure allow sustainedrelease of the SPM. In non-limiting embodiments, the SPM loaded liposomes create a depot ofthe SPM molecules that allows the controlled release of the molecule for up to 11 days in vitroor in vivo.In some embodiments, the liposomes may further comprise one or more additional agents suchas but not limited to imaging agents, co-drugs, excipients. In some embodiments, the liposomesare surface modified liposomes.The present disclosure further provides a method of obtaining a vehicle encapsulatedspecialized pro-resolution mediator (SPMs). In some embodiments, the method of obtainingthe vehicle encapsulated SPM comprises active loading of the SPM into the vehicle.In another embodiment, the present disclosure provides a method of obtaining an SPM loadedliposome. In some embodiments, the method of obtaining the SPM loaded liposome comprisesactive loading of the SPM into the liposome.In some embodiments, the method of obtaining the SPM loaded liposome comprisesestablishing a differential pH gradient across the lipid bilayer to drive the SPM molecule intothe intraliposomal space.In some embodiments, the SPM is RvD1 and the method of obtaining the RvD1 loadedliposome follows a remote-loading strategy.In a non-limiting embodiment, the method of obtaining the SPM loaded liposome comprises -- Dissolving lipids in defined molar ratios in chloroform- Depositing lipids in the form of thin films in a round bottom flask by evaporatingchloroform- Hydration of thin films of liposome forming lipids with a solvent to generate vesicle;- Extrusion of the vesicles through a filter of desired pore size to generate liposome ofdesired size; and- Pelleting and re-suspension of the liposomes in SPM containing solution at conditionsthat facilitate loading of the SPM into the liposomes- to obtain the SPM loaded liposome.In some embodiments, the method further comprises washing of the obtained SPM-loadedliposomes to remove the excess unloaded SPM from the extra-liposomal environment.In some embodiments, SPM is RvD1 and the method of obtaining the RvD1 loaded liposomecomprises -- Hydration of thin films of liposome forming lipids with a solvent to generate vesicle;- Extrusion of the vesicles through a filter of desired pore size to generate liposome ofdesired size;- Pelleting and re-suspension of the liposomes in RvD1 containing solution at conditionsthat facilitate loading of the RvD1 into the liposomes; and- Optionally, washing of the obtained RvD1 loaded liposomes.In some embodiments, the liposome is formed by ampiphilic lipids.In exemplary embodiments, the liposome is formed by lipids selected from a group comprisingdipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and methoxy-poly(ethyleneglycol)2000-distearoylphosphatidylethanolamine (DSPE-PEG2000) or a combination thereof, optionallyalong with one or more sterol(s).In some embodiments, the liposome is formed by lipids selected from a group comprisingdipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and methoxy-poly(ethyleneglycol)2000-distearoylphosphatidylethanolamine (DSPE-PEG2000) or a combination thereof, optionallyalong with cholesterol.In some embodiments, the liposome is formed by about 40% to about 94% by mole of DPPC;about 1% to about 50% of DSPE-PEG2000; and, optionally about 0% to about 30% of sterol,preferably cholesterol.In some embodiments, wherein the liposome is formed by 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), methoxy-poly(ethyleneglycol)2000-distearoylphosphatidyletholamine (DSPE-PEG2000), and sterol, preferably cholesterol at aratio of about 85:5:10 by mole.In some embodiments, the solvent employed for hydration of the lipid film is selected fromsolvents such as but not limited to calcium acetate, barium acetate, and magnesium acetate orany combination thereof.In preferred embodiments, the solvent employed for hydration is calcium acetate having a pHof about 6.In a non-limiting embodiment, the hydration may be achieved by addition of aqueous solutions,for example through pipettes, to thin films of lipids.In some embodiments, the extrusion is performed through filters having pore size ranging fromabout 100 nm to about 5μm.In a preferred embodiment, the extrusion is performed through filters having pore size rangingfrom about 150 nm to about 1μm.In another preferred embodiment, the extrusion is performed through filters having pore sizeranging from about 151 nm to about 900nm.In an exemplary embodiment, the extrusion is performed through filters having pore sizeranging from about 300 nm to about 500 nm.In some embodiments, SPM containing solution comprises solvent(s) selected from a groupcomprising sodium sulfate, lithium sulfate, and potassium sulfate acetate or any combinationthereof.In some embodiments, the SPM containing solution comprises about 50ng SPM / mL solvent toabout 4000ng SPM / mL solvent.In some embodiments, the SPM is RvD1 and the RvD1 containing solution comprises one ormore solvents selected from a group comprising sodium sulfate, lithium sulfate, and potassiumsulfate or any combination thereof. In some embodiments, the RvD1 containing solutioncomprises about 50ng RvD1 / mL solvent to about 4000ng RvD1 / mL solvent. In someembodiments, the SPM containing solution has a pH of about 4.In exemplary embodiments, the SPM containing solution is an RvD1 containing sodium sulfatesolution having a pH of about 4.In some embodiments, the solvent employed for hydration of thin film(s) of liposome has a pHranging from about 5 to about 7, preferably about 6; and the SPM containing solution has a pHranging from about 2 to about 4.5, preferably about 4. In a non-limiting embodiment, saiddifference in pH creates a differential pH gradient across the lipid bilayer to drive the SPMmolecule into the intraliposomal space.In some embodiments, the pelleting and re-suspension of the liposomes in SPM containingsolution performed is at a temperature of about 4°C to about 8°C for about 10 minutes to about20 minutes. In a non-limiting embodiment, the pelleting is performed by centrifugation at aspeed of about 20000g to about 40000g, preferably about 30000g.In some embodiments, the washing is performed with a solvent selected from a groupcomprising Phosphate Buffered Saline (PBS), Normal Saline (NS), and Hank's Balanced SaltSolution (HBSS) or any combination thereof, preferably PBS.In some embodiments, thin films of lipids are hydrated with about 120 mM calcium acetate(pH about 6) to generate vesicles. These vesicles are extruded through filters of different poresizes (about 1 μm, about 400 nm, and about 100 nm) to generate liposomes of desired sizes.Finally, the liposomes are pelleted and resuspended in RvD1-containing sodium sulfatesolution (pH about 4) and loaded at about 50°C for about 1.5 hours. After loading, theformulation is washed twice in PBS to obtain the rvD1 loaded liposomes.In some embodiments, the aforesaid method is able to achieve an encapsulation efficiency ofabout 10% to about 100%.In exemplary embodiments, the method of the present disclosure provides an encapsulationefficiency of preferably about 43% to about 99%.The present invention further provides a composition comprising the SPM-loaded vehiclesdescribed above. Particularly, provided herein is a composition comprising the RvD1 loadedliposomes of the present disclosure.In some embodiments, the composition further comprises one or more pharmaceuticallyacceptable excipients or additives.In some embodiments, the pharmaceutically acceptable excipients or additives are selectedfrom a group comprising solvents, co-solvents, solubilizing, wetting, suspending, emulsifyingor thickening agents, chelating agents, antioxidants, reducing agents, antimicrobialpreservatives, buffers, pH adjusting agents, bulking agents, protectants, tonicity adjustors, andother special additives.In a non-limiting embodiment, the pharmaceutically acceptable excipients or additives areselected from a group comprising saline and phosphate buffered saline (PBS) or a combinationthereof.In some embodiments, the composition is a sustained release formulation.In some embodiments, the composition is formulated into an injectable formulation. In anembodiment, the composition is formulated as a liquid, ready-to-inject suspension.In a non-limiting embodiment, the composition is formulated into an injection. In a nonlimitingembodiment, the injection may be administered through intraarticular, intramuscular,intravenous or subcutaneous routes.Said injection, in preferred embodiments, is fit for local administration, at the joint, fortreatment or prophylaxis of joint-related diseases. Therefore, in another preferred embodiment,the injection is fit for intraarticular administration.The SPM-loaded liposomes, preferably the RvD1 loaded liposomes of the present disclosurefind application in the prophylaxis and / or treatment of joint related diseases such as but notlimited to Osteoarthritis (OA).Accordingly, the present invention provides a method of preventing or treating joint relateddiseases such as but not limited to Osteoarthritis (OA) comprising administering the SPMloaded vehicle or the composition comprising the SPM-loaded vehicle as described above to asubject in need thereof.In some embodiments, the present invention provides a method of preventing or treating jointrelated diseases such as but not limited to Osteoarthritis (OA) comprising administering theSPM loaded liposome or the composition comprising the SPM-loaded liposome as describedabove to a subject in need thereof.In some embodiments, the present invention provides a method of preventing Osteoarthritis(OA) comprising administering the RvD1 loaded liposome or the composition comprising theRvD1-loaded liposome as described above to a subject in need thereof.In some embodiments, the present invention provides a method of treating Osteoarthritis (OA)comprising administering the RvD1 loaded liposome or the composition comprising the RvD1-loaded liposome as described above to a subject in need thereof.In a non-limiting embodiment, the method of treating OA comprises administering the SPMloaded liposome or the composition comprising the SPM-loaded liposome as described aboveto a subject in need thereof at a dosage ranging from about 18 ng / dose to about 36 ng / dose.In a non-limiting embodiment, the aforesaid methods may be employed for treatment ofOsteoarthritis (OA) arising from trauma, injury, age-related wear and tear or obesity.In some embodiments, the administration is by way of injection. In a non-limiting embodiment,the injection may be administered through intraarticular, intramuscular, intravenous orsubcutaneous routes.In some embodiments, the administration is by way of local injection.In some embodiments, the injection is an intraarticular injection.The SPM loaded liposomes show sustained release upon administration. Without intending tobe limited by theory, smaller liposomes show longer retention than larger liposomes. This couldbe due to the saturation of phagocytic clearance by synovial macrophages due to a highernumber of smaller particles present in the same weight of lipids compared to larger sizedliposomes.Chronic low-grade inflammation is a major driver of tissue damage in tissue related diseaseslike OA. Several approaches have attempted to treat OA by arresting the associatedinflammation by direct intraarticular injection of the active ingredient (like anti-inflammatoryantibodies and ω-3 fatty acids). However, limited in vivo retention of such active ingredientslimits their therapeutic potential.The method of prophylaxis and / or treatment of OA of the present disclosure involvingintraarticular delivery of the SPM loaded liposome or the composition comprising the SPMloaded liposome, can help bypass the low oral bioavailability of drugs by generating a highlocal drug concentration. This allows release of the drug in a sustained fashion, reducing thedosage frequency and total administered dosage.In an exemplary embodiment, the SPM loaded liposome shows intraarticular retention for atleast about 9 days.In a non-limiting embodiment, the SPM loaded liposome is expected to show intraarticularretention for about 1 days to about 15 days.In a non-limiting embodiment, the SPM loaded liposome is expected to show intraarticularretention for about 9 days to about 15 days.In some embodiments, the above method reduces joint damage by about 4 fold to about 10 foldas compared to an untreated subject.In some embodiments, the above defined methods for prophylaxis / prevention or treatment ofOA are employed independently or in combination with other treatment modules for the sameor different indication(s).OA is typically characterized by progressive loss of cartilage, pain, damage to the subchondralbone, and eventual loss of function of the affected joint in humans.The methods employing the SPM loaded, preferably RvD1 loaded liposomes and / orcompositions comprising the said loaded liposomes trigger the preferential polarization of pro-inflammatory M1 cells towards pro-resolution M2 cells, reduce levels of pro-inflammatorycatabolic mediators like ADAMTS5 and MMP13, exert analgesic effect for a certain durationpost-injection and lead to maintenance of a high percentage of healthy and non-hypertrophicchondrocytes.In some embodiments, provided herein is a method of prophylaxis of OA, specifically targetedtowards OA, comprising administration of the liposome encapsulated SPM or compositioncomprising the same. Without intending to be limited by theory, the exact source of OA-relatedallodynia is not known, but the Transient Receptor Potential (TRP) family of mediators isknown to play a critical role in response to mechanical stimuli, including those inducing pain.Members of this family, especially TRPV1 and TRPV4, are associated with the severity of painin OA. SPMs such as RvD1 has been shown to have an anti-nociceptive effect by targetingmembers of this family, especially TRPV3, TRPV4, and TRPA1. Sustained presence of SPMssuch as RvD1 in the affected knee joint may help efficiently alleviate OA-associated pain,especially under a prophylactic regimen. The pain relief could be important translationally asnot only would it provide immediate benefit but would also ensure patient compliance.Taken together, the aforesaid methods reduce the net inflammatory activity in joint relateddiseases such as OA and allow maintenance of joint integrity.The present disclosure further provides use of the SPM loaded vehicle or the compositioncomprising the SPM-loaded vehicle as described above for the prophylaxis or management ofjoint related diseases such as but not limited to OA.In preferred embodiments, the present disclosure provides use of the RvD1 loaded liposome orthe composition comprising the RvD1 loaded liposome for the prophylaxis or management ofjoint related diseases such as but not limited to OA.Further provided herein is the SPM loaded vehicle or the composition comprising the SPMloadedvehicle for use in the prevention or management of joint related diseases such as butnot limited to OA.In another embodiment, the present disclosure provides the RvD1 loaded liposome or thecomposition comprising the RvD1 loaded liposome for use in the prevention or managementof joint related diseases such as but not limited to OA.In some embodiments, the present disclosure provides use of the SPM loaded vehicle describedabove in the manufacture of a medicament for the prophylactic and / or therapeutic treatment ofjoint related diseases such as but not limited to OA.In some embodiments, the present disclosure provides use of the RvD1 loaded liposomedescribed above in the manufacture of a medicament for the prophylactic and / or therapeutictreatment of joint related diseases such as but not limited to OA.In some embodiments, the said use allows sustained release for about 1 day to about 15 days.In some embodiments, the said use allows sustained release for about 9 days to about 15 days.In terms of mechanism, without intending to be restricted by this theory, RvD1 polarizesmacrophages to a pro-resolution M2 phenotype instead of the M1 phenotype, in both treatmentand prophylactic regimens. Ratio of M2 / M1 cells increases with the administration of liposomeencapsulated RvD1, leading to reduced inflammatory and catabolic markers such as MMP13and ADAMTS5. The present disclosure further provides a kit having components selected froma group comprising the SPM loaded liposomes as described above, one or morepharmaceutically acceptable carrier(s), the composition comprising the SPM loaded liposomes,means for administration of the SPM loaded liposomes and an instruction manual for enablinguse of the kit or any combination thereof.In some embodiments, the present disclosure provides a kit having components selected froma group comprising the RvD1 loaded liposomes as described above, one or morepharmaceutically acceptable carrier(s), means for administration of the RvD1 loaded liposomesand an instruction manual for enabling use of the kit or any combination thereof.In some embodiments, the means for administration of the loaded liposome is a syringe.Accordingly, in some embodiments, the kit of the present disclosure contains componentsselected from a group comprising the RvD1 loaded liposomes as described above, one or morepharmaceutically acceptable carrier(s), one or more syringes for administration of the RvD1loaded liposomes and an instruction manual for enabling use of the kit or any combinationthereof.In some embodiments, the kit comprises further components for aftercare of the treated subjectsuch as but not limited to dressing(s), means for temperature regulated compression, topicalointments and additional medication.The present disclosure further provides pre-filled pens or syringes comprising the SPM loadedvehicle or the composition comprising the SPM-loaded vehicle as described above.In some embodiments, the present disclosure provides pre-filled pens or syringes comprisingthe RvD1 loaded liposomes or the composition comprising the RvD1 loaded liposomes asdescribed above.Said pre-filled pens or syringes allow ease of administration and self-administration of the SPMloaded vehicle, preferably the RvD1 loaded liposomes, for the prophylaxis or management ofjoint related diseases such as but not limited to OA.It is to be understood that the foregoing descriptive matter is illustrative of the disclosure andnot a limitation. While considerable emphasis has been placed herein on the particular featuresof this disclosure, it will be appreciated that various modifications can be made, and that manychanges can be made in the preferred embodiments without departing from the principles ofthe disclosure. Those skilled in the art will recognize that the embodiments herein can bepracticed with modification within the spirit and scope of the embodiments as described herein.Similarly, additional embodiments and features of the present disclosure will be apparent toone of ordinary skill in art based upon description provided herein.Descriptions of well-known / conventional methods / steps and techniques are omitted so as tonot unnecessarily obscure the embodiments herein. Further, the disclosure herein provides forexamples illustrating the above-described embodiments, and in order to illustrate theembodiments of the present disclosure certain aspects have been employed. The examples usedherein for such illustration are intended merely to facilitate an understanding of ways in whichthe embodiments herein may be practiced and to further enable those of skill in the art topractice the embodiments herein. Accordingly, the following examples should not be construedas limiting the scope of the embodiments herein.EXAMPLES:EXAMPLE 1: Liposome synthesisLiposomes were synthesized by the thin-film lipid hydration method. Briefly, the lipids DPPC,DSPE-PEG, and cholesterol were dissolved in chloroform and mixed in their respective molarratios (85:5:10) in a round bottom flask. The chloroform was evaporated using a rotatoryevaporator (DLAB RE100 Pro) for about 45 mins, thus forming thin lipids films. The filmsgenerated were hydrated using suitable solutions as per the intended experiments (AF750 inPBS for in vivo retention experiments, calcium acetate for all RvD1 loading experiments) atabout 45 °C for about 20 mins. The vesicles were then collected and passed through 1 μm,400 nm and 100 nm membranes to generate liposomes of a defined size. The sizes andmorphology of particles were then measured using dynamic light scattering (DLS) (fig. 1A)and cryo-TEM (fig. 1B). The sizes of liposomes obtained were about 150 nm, about 350 nm,and about 900 nm (fig. 1A). To test the stability of the liposomes, the liposomes wereincubated in PBS for up to about 10 days at about 37°C. The sizes of liposomes were measuredusing Malvern Zetasizer μV. It was observed that the liposomes were stable and maintainedtheir size in PBS for more than about 10 days (fig. 1C).EXAMPLE 2: Liposome loadingFor the purposes of comparison, RvD1 was initially loaded passively by hydrating dry filmsof DPPC, DSPE:PEG and cholesterol at molar ratio 85:5:10 with about 1 mL of a solution ofRvD1 in PBS comprising about 1 μg / mL of RvD1. The concentration of RvD1 entrapped inthe liposomes was measured using a standard curve via HPLC (fig. 2A). The encapsulationefficiency when RvD1 was loaded passively was found to be less than about 1%. The lowencapsulation efficiency could be because at pH 7.4, majority of the molecules are ionizedand have negligible solubility in the lipid bilayer, and total combined intraliposomal volumeis about 102-103 fold lower than the total bulk volume of the RvD1 suspension.To overcome this challenge of low loading, RvD1 was then loaded into the liposomes ofExample 1 actively by employing a differential pH gradient across the lipid bilayer to drivethe RvD1 molecule into the intraliposomal space.Thin films of lipids (described in example 1) were hydrated with about 120 mM calciumacetate (pH=6) to generate multilamellar vesicles. These vesicles were extruded through filtersof different pore sizes (about 1 μm, about 400 nm, and about 100 nm) to generate liposomesof desired sizes. Finally, the liposomes were pelleted and resuspended in RvD1-containingsodium sulfate solution (pH=4) and loaded at about 50 °C for about 1.5 hours. After loading,the RvD1-loaded liposomes were washed twice in PBS. This strategy provided anencapsulation efficiency of about 71±28% and loading of about 35.7±16.15 ng / mg of lipid.RvD1 loading in liposomes was tunable and RvD1 were loaded at various different levels -initially starting with about 50ng / mg lipid, about 200ng / mg lipid and about 2000ng / mg lipidto yield liposomes having all the way up to about 1065±92 ng RvD1 / mg liposomes) (fig. 2B).Since RvD1 is extremely potent and works at pico- and nano-molar ranges, lipo-RvD1 withlower loading (about 35.7±16.15 ng / mg of lipid) was used for subsequent experiments.The above experiment was repeated with Resolvin E1 and aspirin-triggered RvD1(AT-RvD1)as candidates for loading into liposomes by the above-described mechanism of active loading.The loading experiments with Resolvin E1 and aspirin-triggered RvD1(AT-RvD1) intoliposomes using the active loading strategy revealed high encapsulation efficiencies of about17.17±0.14% and about 55.5±1.4% respectively.EXAMPLE 3: Effect of cholesterol concentration on intraliposomal retentionThe intraliposomal retention of small-molecule drugs over time directly correlates with theircomposition, especially cholesterol concentration. In order to understand and ascertain theeffect of cholesterol concentration on liposomal loading and drug retention, lipo-RvD1 havingabout 10%, about 20% and about 30% cholesterol were prepared as per Examples 1 and 2.While the percentage of cholesterol in the lipid formulations was not found to affect RvD1loading (Table 1, fig. 2C), 10% cholesterol formulations showed slower release in PBS thanother formulations containing higher amounts of cholesterol (Table 2, fig. 3A).Table 1: Effect of cholesterol on RvD1 loadingTable 2: Effect of cholesterol on RvD1 retention in liposomes*ND - Not determined10% cholesterol content was employed for all subsequent experiments.EXAMPLE 4: In-vitro and in-vivo sustained release studies - effect of liposome onretentionTo test temporal release of RvD1 in vitro, the lipo-RvD1 of Example 2 (comprising about35.7±16.15 ng of RvD1 / mg of lipid and 10% cholesterol) were incubated in PBS at 37°C forvarious time intervals. Drug remaining in the liposomes was quantified using HPLC. It wasfound that the RvD1 molecules were retained intra-liposomally for at least about 11 days (fig.3B).Similarly, to evaluate the sustained release of RvD1 from the lipo-RvD1 of Example 2, insynovium-like conditions, the lipo-RvD1 was incubated in synovial fluid obtained from jointsof patients undergoing joint replacement surgery at 37ºC for various time intervals. Atintervals of 0, 5 and 10 days, the liposomes were collected, and the drug retained wasquantified using HPLC. It was found that the RvD1 molecules were retained intra-liposomallyfor about 11 days (figure 12).For testing retention in vivo, the liposomes of Example 1 were synthesized to comprisefluorescent dye AF750. Said dye, loaded into the liposome, allowed for sensitivequantification of fluorescence through live tissues since its emission spectrum has littleoverlap with tissue autofluorescence. For purposes of comparison, free dye and theencapsulated dye were injected into mice through intraarticular injection. Data showed thatintraarticular injected liposomes had significantly higher retention than free dye from day 1onwards. While more than 90% of the free dye was cleared within 1 day, liposomeencapsulateddye signal was present even after 14 days (fig. 4A, 4B).The above therefore shows that the liposome encapsulated RvD1 of the present disclosureallows for sustained release of the RvD1 and helps avoid rapid diffusion of the drug out of thejoint.EXAMPLE 5: Effect of particle sizeIntraarticular retention of RvD1 loaded liposomes of three different sizes - about 150nm,about 350nm, and about 900 nm prepared as per Examples 1 and 2 was tested by the samemethod as described in Example 4 - basing reliance on the fluorescent signal from liposomesloaded with fluorescent dyes. Results are depicted in the below table.Table 3: Effect of liposome size on retentionResults showed that smaller liposomes (about 100-500 nm, more preferably about 350nm) hadlonger retention than larger liposomes (about ~900 nm) (Table 3, fig. 4C).EXAMPLE 6: Prophylactic effect of Lipo-RvD1 on post-traumatic OAThe surgical model of destabilization of the medial meniscus (DMM) is a reliable model forpost-traumatic OA (PTOA), which is prevalent in about 12-15% of all osteoarthritis (OA)patients. The medial meniscus is soft fibrocartilage that is located between the articulatingsurfaces and absorbs mechanical shock. Surgically cutting this tissue results in contactbetween the two articulating surfaces and visible OA-like changes over about 1-3 months.DMM surgery was performed in mice and a prophylactic dosing regimen was employed byinjecting freshly synthesized lipo-RvD1 intraarticularly at weeks 1, 4, and 8 after surgery at adosage of about 25ng / joint / dose (fig. 5A). Weight monitoring showed no adverse effects asanimals in groups continued to gain weight at steady rate (Table 4, fig. 5B).Table 4: Effect of administration on lipo-RvD1 on weight of miceFurther studies showed that liposomes could impede OA progression by maintaining theoverall joint integrity. Specifically, it was observed that the lipo-RvD1 treated mice had awell-maintained matrix in all the cartilage layers compared to free-RvD1 and untreated mice,which in some animals, suffered severe denudation (Table 5, Figure 5D). The parameters ofjoint damage like cartilage loss, chondrocyte apoptosis, and formation of osteophytes can bequantified on a scale of 0-24 using guidelines laid by Osteoarthritis Research SocietyInternational (OARSI). The OARSI scores were calculated post-euthanasia, 3 months postsurgery.These scores are shown in Table 5.Table 5: OARSI scores**Outlier (analyzed through Grubbs outlier analysis)Additionally, the Safranin-O-stained histology sections of different groups of mice alsoshowed a higher percentage of healthy and non-hypertrophic chondrocytes in lipo-RvD1treated animals (fig. 5C). Untreated DMM mice had higher levels of M1 cells which isindicative of a pro-inflammatory phenotype (Table 6, fig. 6A, 6B).Table 6: iNOS+ cells in synoviumFurther, Lipo-RvD1 treatment was found to trigger preferential polarization towards M2 cells(Table 7, fig. 6C, 6D).Table 7: CD206+ cells in synoviumIt was further observed that Lipo-RvD1 successfully decreased the ratio of M1 / M2 cells (Table8, fig. 6E).Table 8: Ratio of M1 / M2 cellsIt was therefore seen that lipo-RvD1 can reduce the net inflammatory activity of the synoviumby reducing M1 cells and promoting clearance of debris and other inflammatory factors byincreasing pro-resolution M2 cells in the joint more efficiently that free RvD1.It was also observed that the treated OA joint also had reduced expression of pro-inflammatorycatabolic mediators like ADAMTS5 and MMP13 (fig. 7A, 7B).EXAMPLE 7: Therapeutic effect of Lipo-RvD1 on post-traumatic OATo test therapeutic efficacy of lipo-RvD1, a treatment regimen was designed wherein the lipo-RvD1 formulation was administered about 4 weeks and about 8 weeks after DMM surgery ata dosage of about 25ng / joint / dose (fig. 8A). This timeline was selected since OA-like changesin cartilage begin to appear within about 2 weeks after the DMM surgery. In this regimen, thenumber of IA interventions were reduced (two administrations instead of three administrationsemployed for prophylactic treatments). Results suggest that even though the free RvD1partially arrested the damage (as seen from Safranin-O-stained sections (fig. 8B)), it was notsufficient to prevent functional deterioration, as observed from OARSI scoring. On thecontrary, intraarticular lipo-RvD1 administration was much more effective in treating thedamage (Table 9, fig. 8B, 8C).Table 9: OARSI scoresSimilar to the prophylactic study, lipo-RvD1 treatment decreased the levels ofproinflammatory M1 macrophages in the synovial membrane (Table 10, fig. 9A, 9B) whilesimultaneously increasing the levels of pro-resolution M2 macrophage (Table 11, fig. 9C, 9D).Table 10: iNOS+ cells in synoviumTable 11: CD206+ cells in synoviumBesides, results also showed that administration of lipo-RvD1 in a therapeutic regimedecreased the ratio of M1 / M2 cells in the synovial membrane (Table 12, fig. 9E).Table 12: Ratio of M1 / M2 cellsCatabolic enzymes like MMP13 and ADAMTS5, which are known to be major drivers ofdamage, were also upregulated in the cartilage of mice that had undergone surgery, as seen inIHC images. It was observed that the lipo-RvD1 treatment reduced the expression of thesedamaging enzymes (fig. 10A, 10B).EXAMPLE 8: Effect of Lipo-RvD1 on symptoms of post-traumatic OAThe effect of lipo-RvD1 on two major clinical symptoms associated with OA: osteophytes andpain was analyzed in this experiment. The same dosing regimen as provided in Figure 7 wasfollowed. MicroCT data showed that surgically induced OA resulted in increase of bonygrowth in the joint which was inhibited by both free and lipo-RvD1 (fig. 11A). Subchondralbone was analyzed for trabecular thickness, spacing and bone vs total volume. Theobservations are provided in Tables 13-15.Table 13: Effect of Lipo-RvD1 on symptoms of OA -Trabecular spacingTable 14: Effect of Lipo-RvD1 on symptoms of OA -Trabecular thicknessTable 15: Effect of Lipo-RvD1 on symptoms of OA - bone vs total volumeIt was seen that both free and lipo-RvD1 treatments prevented calcification of ectopictrabecular structures (fig. 11B-D).Pathological pain (allodynia) is one of the main clinical symptoms of OA. To test if lipo-RvD1formulations decreased pain in case of post-traumatic OA, the pain threshold of mice was testedusing Von Frey filaments. It was observed that administration of lipo-RvD1 was more effectivein alleviating the allodynia as compared to free RvD1 and no treatment (Table 16, fig. 11E).Table 16: Effect of Lipo-RvD1 on symptoms of OA - alleviation of allodyniaWhile only DMM operated and free drug administered group had low pain threshold (less thanabout 2g), lipo-RvD1 injected animals showed close to about 4g which was closer to Shamcontrols. This analgesic effect of lipo-RvD1 lasted upto about 3 days post injection.EXAMPLE 9: Setting-up an obesity induced OA (ObOA) mouse modelObesity is characterized by an increase in body weight due to the storage of excessive fat inadipose tissue. This disorder was modeled in mice by providing ad libitum access to specializeddiets which are enriched in fat. The mice were fed with a specialized feed containing 60% fatby calorie content to generate overweight mice. A statistically significant difference wasobserved between the weights of the normal diet and HFD-fed mice from the 8th week afterthe commencement of feeding (fig. 13a). Obese patients often show systemic dyslipidemia andupregulated low-density lipoprotein fraction of cholesterol (LDL-c), triglycerides, andcholesterol. Accordingly, the total cholesterol (TC) was also higher in the serum of overweightmice than in their leaner counterparts (figure 13b). LDL-c also increased with dietary fat inmice (fig.13c) and the ratio of both LDL-c (fig. 13d) and TC (fig. 13e) to the high-densitylipoprotein fraction of cholesterol (HDL-c) was higher in overweight mice than in their leanercounterparts. Since these parameters were in alignment with those reported in the literature,high fat-fed mice could be successfully classified as obese.To mimic Obesity related OA (ObOA), DMM surgery (as explained in Example 6) wasperformed in obese mice and compared to DMM in mice fed with standard diet (11% kCal byfat). More severe damage was found to the cartilage in the obese mice than in their leanercounterparts after DMM surgery (p=0.0311) (fig. 13f, 13g). Furthermore, it was observed thatobesity alone was not sufficient to cause OA in mice, as seen from the comparison between thepathologies of lean and obese sham joints, - OA was induced by the DMM surgery and wasmore severe in obese mice (fig.13f, 13g). The articulating surfaces in both the normal dietDMM and high-fat diet DMMs were severely denuded, with more damage present in the latter;damage in obese mice was about 1.5x more severe compared to their leaner counterparts. Thisfinding was in agreement with earlier studies that showed that obesity-induced inflammatorysignaling, and not excessive stress on the joint is the major contributor to the pathology.Example 10: Lipo-RvD1 as a prophylactic candidate for ObOA treatmentA prophylactic dosing regimen was followed by injecting freshly synthesized lipo-RvD1intraarticularly (IA) at weeks 1 and 4 after DMM surgery in the mouse model as described inthe previous example (figure 14a). Lipo-RvD1 arrested the progressing cartilage damage andmaintained the overall joint integrity. Specifically, it was observed that the lipo-RvD1-treatedmice had a well-maintained extracellular matrix and showed about 6-to-8-fold reduction inOARSI scores compared to DMM joints (p=0.0001) which had complete loss of articulatingcartilage at certain sites of damage (fig.14b, 14c). The stained sections showed a higherpercentage of healthy and non-hypertrophic chondrocytes in lipo-RvD1 treated animalscompared to DMM and free RvD1 treated mice (fig. 14b, 14c). Administration of free RvD1did not have any protective effect on the joint and the damage was similar to DMM-onlyanimals.Several inflammatory diseases have an imbalance between the M1 and M2 macrophages. Theratio of M1 / M2 cells is skewed in OA as well and proinflammatory cytokines from M1macrophages drive cartilage damage. DMM mice had higher levels of M1 cells than shammice, which indicates the presence of a proinflammatory environment in the synovium (fig.14d, 14e). Lipo-RvD1 treatment promoted preferential polarization towards M2 cells ascompared to DMM mice (p<0.0001) (fig. 14f, 14g).It was confirmed that the protective effect of lipo-RvD1 was due to the released RvD1 and notthe liposome by itself, because blank liposomes did not have improved pathology compared toDMM joints (fig. 15). Overall, it was observed that lipo-RvD1 formulation increased M2macrophages in the joint which reduced the net inflammatory activity within the synovium andpromoted clearance of debris and other inflammatory factors.Catabolic enzymes like ADAMTS5 and MMP13 released by chondrocytes in OA areconsidered markers of chondrocyte hypertrophy. Chondrocyte hypertrophy in OA disturbscartilage homeostasis and is thought to be a factor that is responsible for OA development.Administration of lipo-RvD1 was found to suppress the expression of the catabolic mediatorsADAMTS5 and MMP13, thus demonstrating its ability to prevent the formation ofhypertrophic chondrocytes in ObOA subjects (fig. 16).Example 11: Lipo-RvD1 as a therapeutic candidate for ObOA treatmentIn clinics, the diagnosis of OA relies on radiographic evidence of joint damage, which is visibleonly when the damage has progressed significantly. Accordingly, therapeutic formulations arecritical for the successful treatment of OA. The therapeutic efficacy of the lipo-RvD1 on ObOAof Example 2 was studied by injecting it at 3 and 6 weeks after DMM surgery. This timelinewas chosen as a suitable therapeutic regimen because cartilage damage is known to start withintwo weeks after DMM surgery (fig. 17a). In this challenging regimen, intraarticular lipo-RvD1administration was much more effective than free RvD1 (p=0.0006) and DMM-only mice(p=0.0001) in maintaining cartilage health (fig. 17b, 17c).Slight downregulation of M1 macrophages was observed in the synovial membrane of theDMM treated joints compared to the lipo-RvD1 treated joints (fig. 17d, 17e). The therapeuticregimen of administration also showed increased levels of pro-resolution M2 macrophages(p=0.0010) (figure 17f, 17g) compared to DMM joints. The lipo-RvD1 treatment furtherreduced the expression of damaging enzymes ADAMTS5 and MMP13 and protected cartilagefrom degradation more efficiently as compared to free RvD1 (fig. 18).Wnt signaling is a major player in OA pathology and β-catenin is a mediator of this signalingand is upregulated in OA. It was observed that lipo-RvD1 administration to OA jointssuppressed the expression of β-catenin in chondrocytes (fig. 19), thus indicatingdownregulation of Wnt signaling. Said suppression was higher in the lipo-RvD1 joints ascompared to the free RvD1 treated joints. This downregulation is further expected to lower thelevels of catabolic enzymes like MMP13, ADAMTS4, and ADAMTS5 in chondrocytes. It wastherefore concluded that Wnt signaling is one of the pathways affected by RvD1 and that moreefficient suppression or downregulation is achievable by lipo-RvD1 as compared to the freedrug.Example 12: Effect of Lipo-RvD1 on SynovitisSynovitis is a hallmark of OA. Increased leukocyte infiltration to the synovium leads tosynovitis and increased production of inflammatory mediators which leads to chondrocytehypertrophy and blocks anabolism. After DMM surgery, synovitis peaks in early stages beforedeclining but persists at a degree higher than that in sham mice throughout the mid and latestages of PTOA22. It was observed that treating DMM mice with lipo-RvD1 reduced thesynovial membrane (SM) thickness (fig. 20 a, b, c, d) and cellularity (fig. 20 e, f, g, h) ascompared to DMM-only mice. Synovial membrane from lipo-RvD1-treated joints was similarin thickness to SM in sham joints in both the therapeutic and prophylactic regimens ofadministration, thus emphasizing the ability of lipo-RvD1 to suppress excessive fibrosis ofsynovial membrane (fig. 20 a, b, c, d). It was further observed that this result also held true forthe total cellularity of the synovial membrane (fig. 20 e, f, g, h).Taken together, lipo-RvD1 treated joints showed a better ability to prevent cells frominfiltrating the inflammatory milieu compared to free RvD1 (fig. 20 g, h).Example 13: Lipo-RvD1 reduces the incidence of OA-associated allodynia - prophylacticregimen vs. therapeutic regimenPathological pain (allodynia) is one of the main clinical symptoms of OA in patients. To test ifresolvin formulations decreased pain in both prophylactic regimen and therapeutic regimens,the pain threshold of mice was once again tested using Von Frey filaments. It was observedthat administration of lipo-RvD1 was more effective in alleviating the allodynia than free RvD1injected mice (p=0.0016) in the prophylactic regimen of administration (fig. 21a) as comparedto the therapeutic regimen (fig. 21b). While the therapeutic regimen showed that lipo-RvD1improved the pain threshold of the limb, the difference was not as statistically significant (fig.21b). The results thus showed that the sustained presence of RvD1 in the affected knee jointhelped alleviate OA-associated pain, especially under a prophylactic regimen.The foregoing description fully reveals the general nature of the embodiments herein that otherscan, by applying current knowledge, readily modify and / or adapt for various applications suchspecific embodiments without departing from the general concept, and, therefore, suchadaptations and modifications should and are intended to be comprehended within the meaningand range of equivalents of the disclosed embodiments. It is to be understood that thephraseology or terminology employed herein is for the purpose of description and not oflimitation. Therefore, while the embodiments in this disclosure have been described in termsof preferred embodiments, those skilled in the art will recognize that the embodiments hereincan be practiced with modification within the spirit and scope of the embodiments as describedherein, without departing from the principles of the disclosure.Any discussion of documents, acts, materials, devices, articles and the like that has beenincluded in this specification is solely for the purpose of providing a context for the disclosure.It is not to be taken as an admission that any or all of these matters form a part of the prior artbase or were common general knowledge in the field relevant to the disclosure as it existedanywhere before the priority date of this application.

Claims

1. A liposome encapsulated specialized pro-resolution mediator (SPM), wherein the liposome has size ranging from about 100nm to about 5μm.

2. The liposome encapsulated SPM as claimed in claim 1, wherein the liposome is formed by lipids selected from a group comprising 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), Egg Phosphatidylcholine (Egg PC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dimyristoyl-sn-glycero- 3-phosphocholine (DMPC), methoxy-poly(ethyleneglycol)2000- distearoylphosphatidylethanolamine (DSPE-PEG2000), or any combination thereof.

3. The liposome encapsulated SPM as claimed in claim 2, wherein the lipid(s) forming the liposome further comprises sterol(s).

4. The liposome encapsulated SPM as claimed in claim 3, wherein the sterol is selected from a group comprising cholesterol, beta-Sitosterol, phytosterol and 20-alpha-Hydroxycholesterol or any combination thereof cholesterol5. The liposome encapsulated SPM as claimed in claim 3, wherein the sterol is cholesterol.

6. The liposome encapsulated SPM as claimed in any of claims 1-5, wherein the liposome is formed by about 40% to about 94% by mole of DPPC; about 1% to about 50% of DSPEPEG2000; and, optionally about 0% to about 30% of sterol by mole.

7. The liposome encapsulated SPM as claimed in any of claims 1-6, wherein the liposome is formed by 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), methoxypoly( ethyleneglycol)2000-distearoylphosphatidyletholamine (DSPE-PEG2000), and sterol at a ratio of about 85:5:10 by mole.

8. The liposome encapsulated SPM as claimed in any of claims 1-7, wherein the SPM is a resolving family molecule selected from a group comprising Resolvin D1 (RvD1), aspirintriggered Resolvin D1 and Resolvin E1 or any combination thereof.

9. The liposome encapsulated SPM as claimed in any of claims 1-8, having size ranging from about 150nm to about 1μm.

10. The liposome encapsulated SPM as claimed in any of claims 1-9, having size ranging from about 300nm to about 500nm.

11. The liposome encapsulated SPM as claimed in any of claims 1-10, comprising SPM at a concentration ranging from about 15 ng / mg of liposomes to about 1200 ng / mg of liposomes.

12. A method of obtaining SPM loaded liposome comprising - a) Hydration of thin film(s) of liposome forming lipid(s) with solvent(s) to generate vesicles; b) Extrusion of the vesicles through a filter to generate liposomes; and c) Pelleting and re-suspending the liposomes in SPM containing solution to obtain the SPM loaded liposome.

13. The method as claimed in claim 12, further comprising washing of the obtained SPM-loaded liposomes to remove excess unloaded SPM from the extra-liposomal environment.

14. The method as claimed in any of claims 12-13, wherein the liposome forming lipid(s) is selected from a group comprising 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), Egg Phosphatidylcholine (Egg PC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2- distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dimyristoyl-sn-glycero-3- phosphocholine (DMPC), methoxy-poly(ethyleneglycol)2000- distearoylphosphatidylethanolamine (DSPE-PEG2000), or any combination thereof; and optionally, comprises sterol(s).

15. The method as claimed in any of claims 12-14, wherein the solvent employed for hydration of the lipid film is selected from a group comprising calcium acetate, barium acetate, and magnesium acetate or any combination thereof.

16. The method as claimed in any of claims 12-15, wherein the extrusion is performed through filters having pore size ranging from about 100 nm to about 5μm.

17. The method as claimed in any of claims 12-16, wherein the SPM is a resolving family molecule selected from a group comprising Resolvin D1 (RvD1), aspirin-triggered Resolvin D1 and Resolvin E1 or any combination thereof.

18. The method as claimed in any of claims 12-17, wherein the SPM containing solution comprises solvent(s) selected from a group comprising sodium sulfate, lithium sulfate, and potassium sulfate acetate or any combination thereof.

19. The method as claimed in any of claims 12-18, wherein the SPM containing solution comprises about 50ng SPM / mL solvent to about 4000ng SPM / mL solvent.

20. The method as claimed in any of claims 12-19, wherein the solvent employed for hydration has a pH ranging from about 5 to about 7, preferably about 6; and wherein the SPM containing solution has a pH ranging from about 2 to about 4.5, preferably about 4.

21. The method as claimed in any of claims 12-20, wherein the pelleting and re-suspension of the liposomes in SPM containing solution is at a temperature ranging from about 37°C to about 60°C for about 0.5 hours to about 2 hours.

22. The method as claimed in claim 13, wherein the washing is performed with a solvent selected from a group comprising Phosphate Buffered Saline (PBS), Normal Saline (NS), and Hank's Balanced Salt Solution (HBSS) or any combination thereof.

23. The method as claimed in any of claims 1222, wherein the obtained SPM loaded liposome has size ranging from about 150nm to about 1μm.

24. The method as claimed in any of claims 12-23, having encapsulation efficiency of about 10% to about 100%, preferably about 43% to about 99%.

25. A composition comprising the liposome encapsulated SPM as claimed in claim 1 and one or more pharmaceutically acceptable excipients or additives.

26. The composition as claimed in claim 25, wherein the composition is a sustained release formulation.

27. The composition as claimed in claim 25, wherein the composition is formulated into an injectable formulation.

28. Use of the liposome encapsulated SPM as claimed in claim 1 or the composition as claimed in claim 25 for the prophylaxis, prevention, management and / or therapeutic treatment of joint related diseases.

29. The use as claimed in claim 28, wherein the liposome encapsulated SPM allows sustained release for about 1 day to about 15 days.

30. The use as claimed in claim 29, wherein the liposome encapsulated SPM allows sustained release for about 9 days to about 15 days.

31. A method of preventing or treating joint related diseases comprising administering the liposome encapsulated SPM as claimed in claim 1 or the composition as claimed in claim 25 to a subject in need thereof.

32. The method as claimed in claim 31, wherein the administration is by way of injection, preferably an intraarticular injection.

33. The method as claimed in claim 31, wherein the method reduces joint damage by about 4 fold to about 10 fold as compared to an untreated subject.

34. A kit comprising one or more of the liposome encapsulated SPM as claimed in claim 1 or the composition as claimed in claim 25, one or more syringes for administration of the liposome encapsulated SPM and optionally, an instruction manual for enabling use of the kit or any combination thereof.

35. A pre-filled pen or syringe comprising the liposome encapsulated SPM as claimed in claim 1 or the composition as claimed in claim 25.