Skip to content
2000
Volume 22, Issue 10
  • ISSN: 1567-2018
  • E-ISSN: 1875-5704

Abstract

Introduction

Rheumatoid arthritis is a chronic autoimmune disease, progressively distinctive cartilage destruction, auto-antibody production, severe joint pain, and synovial inflammation. Nanotechnology represents one of the utmost promising scientific technologies of the 21st century. Nanocarriers could be the key to unlocking its potential by encapsulating Rutin in targeted drug delivery systems, potentially for targeted Rheumatoid arthritis therapy.

Objective

The rationale of current research is to prepare liposomes loaded with a bioflavonoid drug rutin for effective management of rheumatoid arthritis.

Methods

This study investigated the formulation of rutin liposomes using the thin-film hydration technique, also known as the Bangham method. A Box-Behnken design was employed to optimize the formulation parameters. The LP2 batch was then characterized for its mean particle size, zeta potential, shape, diffraction pattern, and thermal properties. Finally, the anti-oxidant and anti-inflammatory potential of the rutin liposomes were evaluated using appropriate assays.

Results

Out of thirteen batches, LP2 was found to be an optimized batch with a mean particle size of 167.1 nm, zeta potential -13.50 mV, and entrapment efficiency of 61.22%. The above results showed higher stability of rutin liposomes. Further characterization of LP2 for morphological assessment, XRD analysis, and DSC revealed its spherical shape less than 1 µm, polycrystalline nature, and thermographic peak at 139°C, respectively. Evaluation of the antioxidant properties and anti-inflammatory potential of LP2 revealed its maximum therapeutic potential in the reduction of inflammation and protein denaturation when evaluated assays.

Conclusion

Rutin liposomal formulation has tremendous potential for the management of Rheumatoid arthritis due to its enhanced bioavailability, anti-oxidant, and anti-inflammatory properties when compared to free rutin.

Loading

Article metrics loading...

/content/journals/cdd/10.2174/0115672018321817241120075724
2025-01-10
2025-12-26
Loading full text...

Full text loading...

References

  1. VenetsanopoulouA.I. AlamanosY. VoulgariP.V. DrososA.A. Epidemiology and risk factors for RA development.Mediterr. J. Rheumatol.202334440441310.31138/mjr.301223.eaf38282942
    [Google Scholar]
  2. XuJ. CopenhaverS.A. CrispinR.T. Rheumatoid arthritis: Pathological mechanisms and modern pharmacologic therapies.Pharmacol. Rev.20217341198126810.1038/s41413‑018‑0016‑9
    [Google Scholar]
  3. SenthelalS. LiJ. ArdeshirzadehS. ThomasM.A. Arthritis.StatPearls.Treasure Island, FLStatPearls Publishing202210.1007/978‑3‑031‑47307‑4_29
    [Google Scholar]
  4. NicholsonL.B. The immune system.Essays Biochem.201660327530110.1042/EBC2016001727784777
    [Google Scholar]
  5. FiresteinG.S. McInnesI.B. Immunopathogenesis of rheumatoid arthritis.Immunity201746218319610.1016/j.immuni.2017.02.00628228278
    [Google Scholar]
  6. RaduA.F. BungauS.G. Management of rheumatoid arthritis: An overview.Cells20211011285710.3390/cells1011285734831081
    [Google Scholar]
  7. RahmanM. BegS. VermaA. Al AbbasiF.A. AnwarF. SainiS. AkhterS. KumarV. Phytoconstituents as pharmacotherapeutics in rheumatoid arthritis: Challenges and scope of nano/submicromedicine in its effective delivery.J. Pharm. Pharmacol.201669111410.1111/jphp.1266127774648
    [Google Scholar]
  8. WuC.Y. YangH.Y. LuoS.F. LaiJ.H. From rheumatoid factor to anti-citrullinated protein antibodies and anti-carbamylated protein antibodies for diagnosis and prognosis prediction in patients with rheumatoid arthritis.Int. J. Mol. Sci.202122268610.3390/ijms2202068633445768
    [Google Scholar]
  9. MuvhulawaN. DludlaP.V. ZiqubuK. MthembuS.X.H. MthiyaneF. NkambuleB.B. Mazibuko-MbejeS.E. Rutin ameliorates inflammation and improves metabolic function: A comprehensive analysis of scientific literature.Pharmacol. Res.202217810616310.1016/j.phrs.2022.10616335257898
    [Google Scholar]
  10. KalitaB. DasM.K. Rutin–phospholipid complex in polymer matrix for long-term delivery of rutin via skin for the treatment of inflammatory diseases.Artif. Cells Nanomed. Biotechnol.201846sup1415610.1080/21691401.2017.141193129226739
    [Google Scholar]
  11. SunC. WeiJ. BiL. Rutin attenuates oxidative stress and proinflammatory cytokine levels in adjuvant-induced rheumatoid arthritis via inhibition of NF-κB.Pharmacology20171001-2404910.1159/00045102728467992
    [Google Scholar]
  12. MalikS. MuhammadK. WaheedY. Nanotechnology: A revolution in modern industry.Molecules202328266110.3390/molecules2802066136677717
    [Google Scholar]
  13. JanakiramanK. KrishnaswamiV. RajendranV. NatesanS. KandasamyR. Novel nano therapeutic materials for the effective treatment of rheumatoid arthritis-recent insights.Mater. Today Commun.20181720021310.1016/j.mtcomm.2018.09.01132289062
    [Google Scholar]
  14. PurohitD. ManchandaD. MakhijaM. RathiJ. VermaR. KaushikD. PandeyP. An overview of the recent developments and patents in the field of pharmaceutical nanotechnology.Recent Pat. Nanotechnol.2021151153410.2174/187221051466620090915440932912128
    [Google Scholar]
  15. RaoD.S. Rheumatoid Arthritis (RA) disease treatment with rutin stabilized nanoparticles.Austin J. Biotechnol. Bioeng.2015221043
    [Google Scholar]
  16. HassanA.S. SolimanG.M. Rutin nanocrystals with enhanced anti-inflammatory activity: Preparation and ex vivo/in vivo evaluation in an inflammatory rat model.Pharmaceutics20221412272710.3390/pharmaceutics1412272736559220
    [Google Scholar]
  17. CoimbraA.T. FerreiraS. DuarteA.P. Genus Ruta: A natural source of high value products with biological and pharmacological properties.J. Ethnopharmacol.202026011307610.1016/j.jep.2020.11307632534112
    [Google Scholar]
  18. GravandiM.M. PourmanouchehriZ. BehboodL. FakhriS. Mohammadi-NooriE. ZhalehM. ShirvaniS. KianiA. FarzaeiM.H. Rutin-loaded chitosan nanoparticles alleviated Freund’s adjuvant-induced rheumatoid arthritis via modulating oxidative stress and inflammatory parameters in Wistar rats.Naunyn Schmiedebergs Arch. Pharmacol.20232712010.1007/s00210‑023‑02902‑x38150015
    [Google Scholar]
  19. BanghamA.D. A new membrane model for biological studies.J. Mol. Biol.196513123825210.1016/S0022‑2836(65)80093‑65859039
    [Google Scholar]
  20. AllenT.M. CullisP.R. Drug delivery systems: Nanoparticles for enhanced therapeutics.Drug Dev. Res.201384441244510.1016/j.addr.2012.09.03723036225
    [Google Scholar]
  21. BozzutoG. MolinariA. Liposomes as an efficient drug delivery system for poorly soluble drugs.Int. J. Mol. Sci.2015166160151603010.1002/9781118444726.ch2
    [Google Scholar]
  22. NsairatH. KhaterD. SayedU. OdehF. Al BawabA. AlshaerW. Liposomes: Structure, composition, types, and clinical applications.Heliyon202285e0939410.1016/j.heliyon.2022.e09394
    [Google Scholar]
  23. UmbarkarM. ThakareS. SurusheT. GiriA. ChopadeV. Formulation and evaluation of liposome by thin film hydration method.J. Drug Deliv. Ther.2021111727610.22270/jddt.v11i1.4677
    [Google Scholar]
  24. GuoR. ZhangX. YanD. YuY. WangY. GengH. WuY. LiuY. KongL. LiX. Folate-modified triptolide liposomes target activated macrophages for safe rheumatoid arthritis therapy.Biomater. Sci.202210249951310.1039/D1BM01520F34904598
    [Google Scholar]
  25. MohantyS. SahooA.K. KonkimallaV.B. PalA. SiS.C. Naringin in combination with isothiocyanates as liposomal formulations potentiates the anti-inflammatory activity in different acute and chronic animal models of rheumatoid arthritis.ACS Omega2020543283192833210.1021/acsomega.0c0430033163815
    [Google Scholar]
  26. JhunJ. MoonJ. RyuJ. ShinY. LeeS. ChoK.H. KangT. ChoM.L. ParkS.H. Liposome/gold hybrid nanoparticle encoded with CoQ10 (LGNP-CoQ10) suppressed rheumatoid arthritis via STAT3/Th17 targeting.PLoS One20201511e024108010.1371/journal.pone.024108033156836
    [Google Scholar]
  27. SujithaS. DineshP. RasoolM. Berberine encapsulated PEG-coated liposomes attenuate Wnt1/β-catenin signaling in rheumatoid arthritis via miR-23a activation.Eur. J. Pharm. Biopharm.202014917019110.1016/j.ejpb.2020.02.00732068029
    [Google Scholar]
  28. SunZ. WeiT. ZhouX. Liposomes encapsulated dimethyl curcumin regulates dipeptidyl peptidase I activity, gelatinase release and cell cycle of spleen lymphocytes in-vivo to attenuate collagen induced arthritis in rats.Int. Immunopharmacol.20186551152110.1016/j.intimp.2018.10.03930408628
    [Google Scholar]
  29. GouveiaV.M. Lopes-de-AraújoJ. Costa LimaS.A. NunesC. ReisS. Hyaluronic acid-conjugated pH-sensitive liposomes for targeted delivery of prednisolone on rheumatoid arthritis therapy.Nanomedicine (Lond.)20181391037104910.2217/nnm‑2017‑037729790395
    [Google Scholar]
  30. SultanaF. NeogM.K. RasoolM. Targeted delivery of morin, a dietary bioflavanol encapsulated mannosylated liposomes to the macrophages of adjuvant-induced arthritis rats inhibits inflammatory immune response and osteoclastogenesis.Eur. J. Pharm. Biopharm.201711522924210.1016/j.ejpb.2017.03.00928315446
    [Google Scholar]
  31. SultanaF. NeogM.K. RasoolM. Withaferin-A, a steroidal lactone encapsulated mannose decorated liposomes ameliorates rheumatoid arthritis by intriguing the macrophage repolarization in adjuvant-induced arthritic rats.Colloids Surf. B Biointerfaces201715534936510.1016/j.colsurfb.2017.04.04628454064
    [Google Scholar]
  32. ParkS.N. LeeM.H. KimS.J. YuE.R. Preparation of quercetin and rutin-loaded ceramide liposomes and drug-releasing effect in liposome-in-hydrogel complex system.Biochem. Biophys. Res. Commun.2013435336136610.1016/j.bbrc.2013.04.09323669037
    [Google Scholar]
  33. VarshneyaA.P. RavikumarP. Formulation and characterization of rutin trihydrate liposomes for topical delivery.Int J Pharm Res201573293710.22376/ijlpr.2023.13.1.SP1.P75‑P82
    [Google Scholar]
  34. XieY. GuoY. CaoS. XueM. FanZ. GaoC. JinB. Hydroxysafflor yellow A attenuates hydrogen peroxide-induced oxidative damage on human umbilical vein endothelial cells.Evid. Based Complement. Alternat. Med.202020201821412810.1155/2020/821412833204292
    [Google Scholar]
  35. PriyaV. Samridhi; Singh, N.; Dash, D.; Muthu, M.S. Nattokinase encapsulated nanomedicine for targeted thrombolysis: Development, improved in vivo thrombolytic effects, and ultrasound/photoacoustic imaging.Mol. Pharm.202421128330210.1021/acs.molpharmaceut.3c0083038126777
    [Google Scholar]
  36. GuoY. ShenL. LuY. LiH. MinK. LiL. YuC. ZhengX. Preparation of rutin-liposome drug delivery systems and evaluation on their in-vitro antioxidant activity.Chin. Herb. Med.20168437137510.1016/S1674‑6384(16)60065‑5
    [Google Scholar]
  37. RoyA.S. DasS. SamantaA. Design, formulation and evaluation of liposome containing isoniazid.Int. J. Appl. Pharm.2018102525610.22159/ijap.2018v10i2.24174
    [Google Scholar]
  38. RaneS. PrabhakarB. Optimization of paclitaxel containing pH-sensitive liposomes by 3 factor, 3 level box-behnken design.Indian J. Pharm. Sci.201375442042610.4103/0250‑474X.11982024302796
    [Google Scholar]
  39. ViolinaD. KalitaB. SimultaneousU.V. Simultaneous UV spectrophotometric estimation and validation of rutin and resveratrol in combined dosage form by Iso absorptive point method.Asian J. Pharm. Anal.20188314715210.5958/2231‑5675.2018.00027.3
    [Google Scholar]
  40. HalevasE.G. AvgoulasD.I. KatsipisG. PantazakiA.A. Flavonoid-liposomes formulations: Physico-chemical characteristics, biological activities and therapeutic applications.Eur. J. Med. Chem. Rep.2022510005910.1016/j.ejmcr.2022.100059
    [Google Scholar]
  41. DhimanA. SinghD. FatimaK. ZiaG. Development of rutin ethosomes for enhanced skin permeation.Int. J. Trad. Med. Appl.20191141010.18689/ijtma‑1000102
    [Google Scholar]
  42. KumarN. RaiA. ReddyN.D. RajP.V. JainP. DeshpandeP. MathewG. KuttyN.G. UdupaN. RaoC.M. Silymarin liposomes improves oral bioavailability of silybin besides targeting hepatocytes, and immune cells.Pharmacol. Rep.201466578879810.1016/j.pharep.2014.04.00725149982
    [Google Scholar]
  43. KubavatK. TrivediP. AnsariH. KongorA. PanchalM. JainV. SindhavG. Green synthesis of silver nanoparticles using dietary antioxidant rutin and its biological contour.Beni. Suef Univ. J. Basic Appl. Sci.202211111510.1186/s43088‑022‑00297‑x
    [Google Scholar]
  44. KarpuzM. Atlihan-GundogduE. DemirE.S. SenyigitZ. Radiolabeled tedizolid phosphate liposomes for topical application: Design, characterization, and evaluation of cellular binding capacity.AAPS PharmSciTech20212226210.1208/s12249‑020‑01917‑433528714
    [Google Scholar]
  45. DuanW. LiH. Combination of NF-kB targeted siRNA and methotrexate in a hybrid nanocarrier towards the effective treatment in rheumatoid arthritis.J. Nanobiotechnology20181615810.1186/s12951‑018‑0382‑x30060740
    [Google Scholar]
  46. ZhangS. HanY. Preparation, characterisation and antioxidant activities of rutin-loaded zein-sodium caseinate nanoparticles.PLoS One2018133e019495110.1371/journal.pone.019495129579133
    [Google Scholar]
  47. BharathiD. BhuvaneshwariV. Synthesis of zinc oxide nanoparticles (ZnO NPs) using pure bioflavonoid rutin and their biomedical applications: Antibacterial, antioxidant and cytotoxic activities.Res. Chem. Intermed.20194542065207810.1007/s11164‑018‑03717‑9
    [Google Scholar]
  48. KumarasingheN. DharmadevaS. GalgamuwaL.S. PrasadinieC. In vitro anti-inflammatory activity of Ficus racemosa L. bark using albumin denaturation method.Ayu201839423924210.4103/ayu.AYU_27_1831367147
    [Google Scholar]
  49. MadhurangaH.D. SamarakoonD.N. In-vitro anti-inflammatory egg albumin denaturation assay.Methodol20231510.23880/jonam‑16000411
    [Google Scholar]
  50. HasanU.H. UttraA.M. RasoolS. Evaluation of in vitro and in vivo anti-arthritic potential of Berberis calliobotrys.Bangladesh J. Pharmacol.201510480781910.3329/bjp.v10i4.23779
    [Google Scholar]
/content/journals/cdd/10.2174/0115672018321817241120075724
Loading
/content/journals/cdd/10.2174/0115672018321817241120075724
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.


  • Article Type:
    Research Article
Keyword(s): anti-inflammatory; antioxidant; box-behnken design; liposomes; Rheumatoid arthritis; rutin
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test