• NARESH KUMAR AHUJA Bhupal Nobels University, Udaipur, Rajasthan, India
  • JITENDRA SINGH RAJAWAT Bhupal Nobels University, Udaipur, Rajasthan, India



Rheumatoid arthritis, Lipid nanoparticle, Inflammation, Drug delivery


Recent advances in science and technology and greatly modified the way we stumble on, deal with and prevent special diseases in all components of human lifestyles. Rheumatoid arthritis (RA) is the most not unusual complex multifactorial joint related autoimmune, chronic, severe systemic inflammatory ailment with unknown etiology completed with increased cardiovascular risks. It is regularly associated with critical synovial joint inflammation, autoantibody production, cartilage/bone tissue destruction, cardiovascular, pulmonary, skeletal disorders and massive inflammatory infiltration which might in the end motive extreme disability, huge complications, premature mortality and decreased life quality. Pro-inflammatory cytokines like IL-1, IL-6, IL-8 and IL-10 were dependable for the induction of inflammation in RA patients. It has a global occurrence of around 1% with the incidence among women being 2-3 times extra in men. Preclinical RA, genetic variables, and environmental factors have all been linked to the disease's etiology. Because there is no known cure for RA, the primary goal of treatment is to achieve the shortest possible illness duration and, if possible, rehabilitation. Current clinical remedies of RA display numerous drawbacks which include excessive doses, common administration, speedy metabolism, bad absorption, low responsiveness, higher cost and serious side consequences. These obstacles have inspired extremely good growth of the studies and to enhance those obstacles, nanoparticles that are able to encapsulating and protecting tablets from degradation earlier than they reach the target site in vivo, might also function drug delivery structures. Bioavailability and therapeutic bioactivity can be improved, and limited emphasis on damaged joints can be allowed. The current study provides a platform for different lipid nanoparticle methods for RA therapy, using the newly developing field of lipid nanoparticles to improve a targeted theranostic device for RA treatment. This review aims to present the most recent major application of lipid nanoparticles as a biocompatible and biodegradable transport device for improving RA concentration on over free drugs by presenting tissue-specific concentrated on of ligand-controlled drug release by modulating nanoparticle composition. Additionally, we also discuss the pivotal demanding situations to be addressed, as well as destiny views. Therefore, it is feasible to claim that nanoparticles will, within the near future, play a critical role in advanced treatment and affected person-particular cures for human diseases which include RA.


Download data is not yet available.


Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Menard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G. 2010 rheumatoid arthritis classification criteria: an American college of Rheumatology/European league against rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569-81. doi: 10.1002/art.27584, PMID 20872595.

Symmons DP. Epidemiology of rheumatoid arthritis: determinants of onset, persistence and outcome. Best Pract Res Clin Rheumatol. 2002;16(5):707-22. doi: 10.1053/berh.2002.0257, PMID 12473269.

Dorner T, Strand V, Cornes P, Gonçalves J, Gulacsi L, Kay J, Kvien TK, Smolen J, Tanaka Y, Burmester GR. The changing landscape of biosimilars in rheumatology. Ann Rheum Dis. 2016;75(6):974-82. doi: 10.1136/annrheumdis-2016-209166, PMID 26964144.

Gibofsky A. Overview of epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis. Am J Manag Care. 2012;18(13);Suppl:S295-302. PMID 23327517.

Handa R, Rao UR, Lewis JF, Rambhad G, Shiff S, Ghia CJ. Literature review of rheumatoid arthritis in India. Int J Rheum Dis. 2016;19(5):440-51. doi: 10.1111/1756-185X.12621, PMID 26171649.

Crielaard BJ, Lammers T, Schiffelers RM, Storm G. Drug targeting systems for inflammatory disease: one for all, all for one. J Control Release. 2012;161(2):225-34. doi: 10.1016/j.jconrel.2011.12.014, PMID 22226771.

Grassi W, De Angelis R, Lamanna G, Cervini C. The clinical features of rheumatoid arthritis. Eur J Radiol. 1998;27;Suppl 1:S18-24. doi: 10.1016/s0720-048x(98)00038-2, PMID 9652497.

Kanazawa T, Nishino J, Tohma S, Tanaka S. Analysis of the affected joints in rheumatoid arthritis patients in a large Japanese cohort. Mod Rheumatol. 2013;23(1):44-9. doi: 10.1007/s10165-012-0636-7, PMID 22466118.

Pfizer. Pfizer value of medicines, Rheumatoid Arthritis and the Value of Treatment Global Policy and International Public Affairs; 2014. Available from: files/health/VOMPaper_RheumatoidArthritis_11-3-2016.pdf. [Last accessed on 10 Jul 2021]

Svendsen AJ, Junker P, Houen G, Kyvik KO, Nielsen C, Skytthe A, Holst R. Incidence of chronic persistent rheumatoid arthritis and the impact of smoking: A historical twin cohort study. Arthritis Care Res. 2017;69(5):616-24. doi: 10.1002/acr.22987, PMID 27390149.

Yang M, Feng X, Ding J, Chang F, Chen X. Nanotherapeutics relieve rheumatoid arthritis. J Control Release. 2017;252:108-24. doi: 10.1016/j.jconrel.2017.02.032, PMID 28257989.

McInnes IB, Schett G. Pathogenetic insights from the treatment of rheumatoid arthritis. Lancet. 2017;389(10086):2328-37. doi: 10.1016/S0140-6736(17)31472-1, PMID 28612747.

Janakiraman K, Krishnaswami V, Rajendran V, Natesan S, Kandasamy R. Novel nano therapeutic materials for the effective treatment of rheumatoid arthritis-recent insights. Mater Today Commun. 2018;17:200-13. doi: 10.1016/j.mtcomm.2018.09.011, PMID 32289062. mtcomm.2018.09.011.

Montecucco F, Mach F. Common inflammatory mediators orchestrate pathophysiological processes in rheumatoid arthritis and atherosclerosis. Rheumatology (Oxford). 2009;48(1):11-22. doi: 10.1093/rheumatology/ken395, PMID 18927189.

Deane KD, Norris JM, Holers VM. Preclinical rheumatoid arthritis: identification, evaluation, and future directions for investigation. Rheum Dis Clin North Am. 2010;36(2):213-41. doi: 10.1016/j.rdc.2010.02.001, PMID 20510231.

Silman AJ, Pearson JE. Epidemiology and genetics of rheumatoid arthritis. Arthritis Res. 2002;4(3);Suppl 3:S265-72. doi: 10.1186/ar578, PMID 12110146.

Liao KP, Alfredsson L, Karlson EW. Environmental influences on risk for rheumatoid arthritis. Curr Opin Rheumatol. 2009;21(3):279-83. doi: 10.1097/BOR.0b013e32832a2e16, PMID 19318947.

Deane KD, El-Gabalawy H. Pathogenesis and prevention of rheumatic disease: focus on preclinical RA and SLE. Nat Rev Rheumatol. 2014;10(4):212-28. doi: 10.1038/nrrheum.2014.6, PMID 24514912.

Aletaha D, F Alasti, JS Smolen. Rheumatoid factor, not antibodies against citrullinated proteins, is associated with baseline disease activity in rheumatoid arthritis clinical trials. Arthritis Res Ther. 2015;17(1):229. doi: 10.1186/s13075-015-0736-9.

C Edwards, C Cooper. Early environmental factors and rheumatoid arthritis. Clin Exp Immunol. 2006;143(1):1-5. doi: 10.1111/j.1365-2249.2005.02940.x, PMID 16367927.

J Newton JL, S Harney SM, B Wordsworth BP, M Brown MA. A review of the MHC genetics of rheumatoid arthritis. Genes Immun. 2004;5(3):151-7. doi: 10.1038/sj.gene.6364045, PMID 14749714.

A Suzuki, R Yamada, X Chang, S Tokuhiro, T Sawada, M Suzuki, M Nagasaki, M Nakayama-Hamada, R Kawaida, M Ono, Ohtsuki M, Furukawa H, Yoshino S, Yukioka M, Tohma S, Matsubara T, Wakitani S, Teshima R, Nishioka Y, Sekine A, Iida A, Takahashi A, Tsunoda T, Nakamura Y, Yamamoto K. Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat Genet. 2003;34(4):395-402. doi: 10.1038/ng1206, PMID 12833157.

RM Plenge, L Padyukov, EF Remmers, S Purcell, AT Lee, EW Karlson, F Wolfe, DL Kastner, L Alfredsson, D Altshuler, Gregersen PK, Klareskog L, Rioux JD. Replication of putative candidate-gene associations with rheumatoid arthritis in >4,000 samples from North America and Sweden: association of susceptibility with PTPN22, CTLA4, and PADI4. Am J Hum Genet. 2005;77(6):1044-60. doi: 10.1086/498651, PMID 16380915.

Y Kochi, Y Okada, A Suzuki, K Ikari, C Terao, A Takahashi, K Yamazaki, N Hosono, K Myouzen, T Tsunoda, Kamatani N, Furuichi T, Ikegawa S, Ohmura K, Mimori T, Matsuda F, Iwamoto T, Momohara S, Yamanaka H, Yamada R, Kubo M, Nakamura Y, Yamamoto K. A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility. Nat Genet. 2010;42(6):515-9. doi: 10.1038/ng.583, PMID 20453841.

Y Okada, C Terao, K Ikari, Y Kochi, K Ohmura, A Suzuki, T Kawaguchi, EA Stahl, FA Kurreeman, N Nishida, Ohmiya H, Myouzen K, Takahashi M, Sawada T, Nishioka Y, Yukioka M, Matsubara T, Wakitani S, Teshima R, Tohma S, Takasugi K, Shimada K, Murasawa A, Honjo S, Matsuo K, Tanaka H, Tajima K, Suzuki T, Iwamoto T, Kawamura Y, Tanii H, Okazaki Y, Sasaki T, Gregersen PK, Padyukov L, Worthington J, Siminovitch KA, Lathrop M, Taniguchi A, Takahashi A, Tokunaga K, Kubo M, Nakamura Y, Kamatani N, Mimori T, Plenge RM, Yamanaka H, Momohara S, Yamada R, Matsuda F, Yamamoto K. Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population. Nat Genet. 2012;44(5):511-6. doi: 10.1038/ng.2231, PMID 22446963.

E Salgado, M Bes-Rastrollo, J de Irala, L Carmona, JJ Goomez Reino. High sodium intake is associated with self-reported rheumatoid arthritis: a cross sectional and case control analysis within the SUN cohort. Medicine (Baltimore). 2015;94(37):e0924. doi: 10.1097/MD.0000000000000924, PMID 26376372.

I Lazurova, I Jochmanova, K Benhatchi, S Sotak. Autoimmune thyroid disease and rheumatoid arthritis: relationship and the role of genetics. Immunol Res. 2014;60 :193-200. doi: 10.1007/s12026-014-8598-9, PMID 25427993.

J Schmitt, K Schwarz, H Baurecht, M Hotze, R Folster Holst, E Rodriguez, YA Lee, A Franke, F Degenhardt, W Lieb, Gieger C, Kabesch M, Nothen MM, Irvine AD, McLean WHI, Deckert S, Stephan V, Schwarz P, Aringer M, Novak N, Weidinger S. Atopic dermatitis is associated with an increased risk for rheumatoid arthritis and inflammatory bowel disease, and a decreased risk for type 1 diabetes. J Allergy Clin Immunol. 2016;137(1):130-6. doi: 10.1016/j.jaci.2015.06.029, PMID 26253344.

RJ Oken, M Schulzer. At issue: schizophrenia and rheumatoid arthritis: the negative association revisited. Schizophr Bull. 1999;25(4):625-38. doi: 10.1093/oxfordjournals.schbul.a033407, PMID 10667736.

P Stolt, C Bengtsson, B Nordmark, S Lindblad, I Lundberg, L Klareskog, L Alfredsson, EIRA Study Group. Quantification of the influence of cigarette smoking on rheumatoid arthritis: results from a population based case-control study, using incident cases. Ann Rheum Dis. 2003;62(9):835-41. doi: 10.1136/ard.62.9.835, PMID 12922955.

JE Hart, F Laden, RC Puett, KH Costenbader, EW Karlson. Exposure to traffic pollution and increased risk of rheumatoid arthritis. Environ Health Perspect. 2009;117(7):1065-9. doi: 10.1289/ehp.0800503, PMID 19654914.

HR Harris, KH Costenbader, F Mu, M Kvaskoff, S Malspeis, EW Karlson, SA Missmer. Endometriosis and the risks of systemic lupus erythematosus and rheumatoid arthritis in the Nurses’ Health Study II. Ann Rheum Dis. 2016;75(7):1279-84. doi: 10.1136/annrheumdis-2015-207704, PMID 26238146.

Sourav Thakur S, Bushra Riyaz B, Akshay Patil A, Amanjot Kaur A, Bhupinder Kapoor B, Vijay Mishra V. Novel drug delivery systems for NSAIDs in management of rheumatoid arthritis: Aan overview. Biomed Pharmacother. 2018;106:1011-23. doi: 10.1016/j.biopha.2018.07.027, PMID 30119166.

CT Kraft, S Agarwal, K Ranganathan, VW Wong, S Loder, J Li J, MJ Delano, B Levi. Trauma-induced heterotopic bone formation and the role of the immune system: A review. J Trauma Acute Care Surg. 2016;80(1):156-65. doi: 10.1097/ TA.0000000000-000883, PMID 26491794.

G Jones, P Nash, S Hall. Advances in rheumatoid arthritis. Med J Aust. 2017;206(5):221-4. doi: 10.5694/mja16.01287, PMID 28301793.

MI Koenders, WB van den Berg. Novel therapeutic targets in rheumatoid arthritis. Trends Pharmacol Sci. 2015;36(4):189-95.

F Yuan, LD Quan, L Cui, SR Goldring, D Wang. Development of macromolecular prodrug for rheumatoid arthritis. Adv Drug Delivery Rev. 2012;64(12):1205-19. doi: 10.1016/j.addr.2012.03.006, PMID 22433784.

Van Vollenhoven RF. Treatment of rheumatoid arthritis: state of the art. Nat Rev Rheumatol. 2009;5(10):531-41. doi: 10.1038/nrrheum.2009.182, PMID 19798027.

Dolati S, Sadreddini S, Rostamzadeh D, Ahmadi M, Jadidi Niaragh F, Yousefi M. Utilization of nanoparticle technology in rheumatoid arthritis treatment. Biomed Pharmacother. 2016;80:30-41. doi: 10.1016/j.biopha.2016.03.004, PMID 27133037.

Tarner IH, Muller Ladner U. Drug delivery systems for the treatment of rheumatoid arthritis. Expert Opin Drug Deliv. 2008;5(9):1027-37. doi: 10.1517/17425247.5.9.1027, PMID 18754751.

Prasad LK, O’Mary H, Cui Z. Nanomedicine delivers promising treatments for rheumatoid arthritis. Nanomedicine (Lond). 2015;10(13):2063-74. doi: 10.2217/nnm.15.45, PMID 26084368.

Mitragotri S, Yoo JW. Designing micro- and nano-particles for treating rheumatoid arthritis. Arch Pharm Res. 2011;34(11):1887-97. doi: 10.1007/s12272-011-1109-9.

Buch MH, Bingham SJ, Bryer D, Emery P. Long-term infliximab treatment in rheumatoid arthritis: subsequent outcome of initial responders. Rheumatology (Oxford). 2007;46(7):1153-6. doi: 10.1093/rheumatology/kem075, PMID 17478470.

Chaudhari K, Rizvi S, Syed BA. Rheumatoid arthritis: current and future trends. Nat Rev Drug Discov. 2016;15(5):305-6. doi: 10.1038/nrd.2016.21, PMID 27080040.

Listing J, Strangfeld A, Kary S, Rau R, Von Hinueber U, Stoyanova Scholz M, Gromnica Ihle E, Antoni C, Herzer P, Kekow J, Schneider M, Zink A. Infections in patients with rheumatoid arthritis treated with biologic agents. Arthritis Rheum. 2005;52(11):3403-12. doi: 10.1002/art.21386, PMID 16255017.

Rao JK, Mihaliak K, Kroenke K, Bradley J, Tierney WM, Weinberger M. Use of complementary therapies for arthritis among patients of rheumatologists. Ann Intern Med. 1999;131(6):409-16. doi: 10.7326/0003-4819-131-6-199909210-00003, PMID 10498556.

Chandrasekar R, Chandrasekar S. Natural herbal treatment for rheumatoid arthritis-a review. Int J Pharm Sci Res. 2017;8(2):368.

Movahedi M, Beauchamp ME, Abrahamowicz M, Ray DW, Michaud K, Pedro S, Dixon WG. Risk of incident diabetes mellitus associated with the dosage and duration of oral glucocorticoid therapy in patients with rheumatoid arthritis. Arthritis Rheumatol. 2016;68(5):1089-98. doi: 10.1002/art.39537, PMID 26663814.

Bahadar H, Maqbool F, Niaz K, Abdollahi M. Toxicity of nanoparticles and an overview of current experimental models. Iran Biomed J. 2016;20(1):1-11. doi: 10.7508/ibj.2016.01.001, PMID 26286636.

Xu L, Qi X, Li X, Bai Y, Liu H. Recent advances in applications of nanomaterials for sample preparation. Talanta 2016;146:714-26.

Y Panahi, M Farshbaf, M Mohammadhosseini, M Mirahadi, R Khalilov, S Saghfi, A Akbarzadeh. Recent advances on liposomal nanoparticles: synthesis, characterization and biomedical applications. Artif Cells Nanomed Biotechnol. 2017;45(4):788-99. doi: 10.1080/21691401.2017.1282496, PMID 28278586.

Heloise R, Danhier F, Preat V, Langer R, Anderson DG. Nanoparticle-based drug delivery systems: a commercial and regulatory outlook as the field matures. Expert Opion Drug Delivery 2017;14(7):851-64.

E Nogueira, AC Gomes, A Preto, A Cavaco, Paulo A. Folate-targeted nanoparticles for rheumatoid arthritis therapy. Nanomedicine 2016;12(4):1113-26. doi: 10.1016/ j.nano.2015.12.365, PMID 26733257.

Q Thao le, Byeon HJ, Lee C, Lee S, Lee ES, Choi HG, Park ES, Youn YS le, HJ Byeon C. Pharmaceutical potential of tacrolimus-loaded albumin nanoparticles having targetability to rheumatoid arthritis tissues. Int J Pharm 2016;497(1-2):268-76. doi: 10.1016/j.ijpharm.2015.12.004, PMID 26657273.

S Behzadi, V Serpooshan, W Tao, MA Hamaly, MY Alkawareek, EC Dreaden, D Brown, AM Alkilany, OC Farokhzad, M Mahmoudi. Cellular uptake of nanoparticles: Journey inside the cell. Chem Soc Rev. 2017;46(14):4218-44. doi: 10.1039/c6cs00636a, PMID 28585944.

TM Ahmed, BM Aljaeid. Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery. Drug Des Dev Ther. 2016;10:483-507. doi: 10.2147/DDDT.S99651, PMID 26869768.

Rao SD. Rheumatoid arthritis (ra) disease treatment with rutin stabilized nanoparticles, Austin. J Biotechnol Bioeng. 2015; 2(2):1043.

Lee SN, Kim HJ, Ha YJ, Park YN, Lee SK, Park YB, Yoo KH. Targeted chemophotothermal treatments of rheumatoid arthritis using gold half-shell multifunctional nanoparticles. ACS. 2012;7(1):50-7.

Kishore N, Raja MD, Kumar CS, Dhanalekshmi U, Srinivasan R. Lipid carriers for delivery of celecoxib: in vitro, in vivo assessment of nanomedicine in rheumatoid arthritis. Eur J Lipid Sci Technol. 2016;118(6):949-58. doi: 10.1002/ejlt.201400658.

Kumar V, Leekha A, Tyagi A, Kaul A, Mishra AK, Verma AK. Preparation and evaluation of biopolymeric nanoparticles as drug delivery system in effective treatment of rheumatoid arthritis. Pharm Res. 2017;34(3):654-67. doi: 10.1007/s11095-016-2094-y, PMID 28097508.

Dewangan AK, Varkey S, Mazumder S. Synthesis of curcumin loaded CMCAB nanoparticles for the treatment of rheumatoid arthritis, IJCEBS; 2015. p. 18-9.

Lee SM, Kim HJ, Ha YJ, Park YN, Lee SK, Park YB, Yoo KH. Targeted chemo-photothermal treatments of rheumatoid arthritis using gold half-shell multifunctional nanoparticles. ACS Nano. 2013;7(1):50-7. doi: 10.1021/nn301215q, PMID 23194301.

Thao le Q, Byeon HJ, Lee C, Lee S, Lee ES, Choi HG, Park ES, Youn YS. Pharmaceutical potential of tacrolimus-loaded albumin nanoparticles having targetability to rheumatoid arthritis tissues. Int J Pharm. 2016;497(1-2):268-76. doi: 10.1016/j.ijpharm.2015.12.004, PMID 26657273.

Kumar R, Singh A, Garg N, Siril PF. Solid lipid nanoparticles for the controlled delivery of poorly water soluble non-steroidal anti-inflammatory drugs. Ultrason Sonochem. 2018;40(A):686-96. doi: 10.1016/j.ultsonch.2017.08.018, PMID 28946474.

Geszke Moritz M, Moritz M. Solid lipid nanoparticles as attractive drug vehicles: composition, properties and therapeutic strategies. Mater Sci Eng C Mater Biol Appl. 2016;68:982-94. doi: 10.1016/j.msec.2016.05.119, PMID 27524099.

Garg NK, Singh B, Tyagi RK, Sharma G, Katare OP. Effective transdermal delivery of methotrexate through nanostructured lipid carriers in an experimentally induced arthritis model. Colloids Surf B Biointerfaces. 2016;147:17-24. doi: 10.1016/j.colsurfb.2016.07.046, PMID 27478959.

Chavan D, Gangode B, Jadhav A, Patil M, Kshirsagar S. Solid lipid nanoparticles: A modern formulation approach in drug delivery system. IJOD. 2017;5(2):56-70.

Arora R, Kuhad A, Kaur IP, Chopra K. Curcumin loaded solid lipid nanoparticles ameliorate adjuvant-induced arthritis in rats. Eur J Pain. 2015;19(7):940-52. doi: 10.1002/ejp.620, PMID 25400173.

Peng LH, Wei W, Shan YH, Chong YS, Yu L, Gao JQ. Sustained release of piroxicam from solid lipid nanoparticle as an effective anti-inflammatory therapeutics in vivo. Drug Dev Ind Pharm. 2017;43(1):55-66. doi: 10.1080/03639045.2016.1220563. PMID 27498809.

Bhalekar MR, Madgulkar AR, Desale PS, Marium G. Formulation of piperine solid lipid nanoparticles (SLN) for treatment of rheumatoid arthritis. Drug Dev Ind Pharm. 2017;43(6):1003-10. doi: 10.1080/03639045.2017.1291666, PMID 28161984.

Raj R, Mongia P, Ram A, Jain NK. Enhanced skin delivery of aceclofenac via hydrogel-based solid lipid nanoparticles. Artif Cells Nanomed Biotechnol. 2016;44(6):1434-9. doi: 10.3109/21691401.2015.1036997, PMID 25919063.

Ye J, Wang Q, Zhou X, Zhang N. Injectable actarit-loaded solid lipid nanoparticles as passive targeting therapeutic agents for rheumatoid arthritis. Int J Pharm 2008;352(1-2):273-9. doi: 10.1016/j.ijpharm.2007.10.014, PMID 18054182.

Gilani SJ, Bin-Jumah MN, Imam SS, Alshehri S, Jahangir MA, Zafar A. Formulation and optimization of nano lipid based oral delivery systems for arthritis. Coatings. 2021;11(5):548. doi: 10.3390/coatings11050548.

Mancini G, Gonçalves LMD, Marto J, Carvalho FA, Simoes S, Ribeiro HM, Almeida AJ. Increased therapeutic efficacy of SLN containing etofenamate and ibuprofen in topical treatment of inflammation. Pharmaceutics. 2021;13(3):328. doi: 10.3390/pharmaceutics13030328, PMID 33802592.

Zhang F, Liu Z, He X, Li Z, Shi B, Cai F. β-sitosterol-loaded solid lipid nanoparticles ameliorate complete freund’s adjuvant-induced arthritis in rats: involvement of NF-кB and HO-1/Nrf-2 pathway. Drug Deliv. 2020;27(1):1329-41. doi: 10.1080/10717544.2020.1818883, PMID 32945205.

Chaudhari PM, Ghodake MV. Development and optimization of solid lipid nanoparticle for topical delivery. J Drug Deliv Ther. 2019;9(5):105-21.

Shinde SV, Nikam S, Raut P, Ghag MK. Lipid nanoparticles for transdermal delivery of celecoxib: an in vitro and in vivo investigation. Indian Drugs. 2019;56(8):38-48.

Chuang SY, Lin CH, Huang TH, Fang JY. Lipid-based nanoparticles as a potential delivery approach in the treatment of rheumatoid arthritis. Nanomaterials (Basel). 2018;8(1):42. doi: 10.3390/nano8010042, PMID 29342965.

Purcell WT, Ettinger DS. Novel antifolate drugs. Curr Oncol Rep. 2003;5(2):114-25. doi: 10.1007/s11912-003-0098-3, PMID 12583828.

Bleyer WA. The clinical pharmacology of methotrexate: new applications of an old drug. Cancer. 1978;41(1):36-51. doi: 10.1002/1097-0142(197801)41:1<36:aid-cncr2820410108>;2-i, PMID 342086.

Grim J, Chladek J, Martínkova J. Pharmacokinetics and pharmacodynamics of methotrexate in non-neoplastic diseases. Clin Pharmacokinet. 2003;42(2):139-51. doi: 10.2165/00003088-200342020-00003, PMID 12537514.

Cutolo M, Sulli A, Pizzorni C, Seriolo B, Straub RH. Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis. Ann Rheum Dis. 2001;60(8):729-35. doi: 10.1136/ard.60.8.729, PMID 11454634.

Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet. 2001;358(9285):903-11. doi: 10.1016/S0140-6736(01)06075-5, PMID 11567728.

Tarner IH, Muller Ladner U. Drug delivery systems for the treatment of rheumatoid arthritis. Expert Opin Drug Deliv. 2008;5(9):1027-37. doi: 10.1517/17425247.5.9.1027, PMID 18754751.

Rahman LK, Chhabra SR. The chemistry of methotrexate and its analogues. Med Res Rev. 1988;8(1):95-155. doi: 10.1002/med.2610080106, PMID 3278183.

Chatterji DC, Gallelli JF. Thermal and photolytic decomposition of methotrexate in aqueous solutions. J Pharm Sci. 1978;67(4):526-31. doi: 10.1002/jps.2600670422, PMID 641762.

Genestier L, Paillot R, Quemeneur L, Izeradjene K, Revillard JP. Mechanisms of action of methotrexate. Immunopharmacology. 2000;47(2-3):247-57. doi: 10.1016/s0162-3109(00)00189-2, PMID 10878292.

Cutolo M, Bisso A, Sulli A, Felli L, Briata M, Pizzorni C, Villaggio B. Antiproliferative and antiinflammatory effects of methotrexate on cultured differentiating myeloid monocytic cells (THP-1) but not on synovial macrophages from patients with rheumatoid arthritis. J Rheumatol. 2000;27(11):2551-7. PMID 11093433.

Hillson JL, Furst DE. Pharmacology and pharmacokinetics of methotrexate in rheumatic disease. Practical issues in treatment and design. Rheum Dis Clin North Am. 1997;23(4):757-78. doi: 10.1016/s0889-857x(05)70359-8, PMID 9361154.

Cronstein BN. The mechanism of action of methotrexate. Rheum Dis Clin North Am. 1997;23(4):739-55. doi: 10.1016/S0889-857X(05)70358-6.

Koch AE, Distler O. Vasculopathy and disordered angiogenesis in selected rheumatic diseases: rheumatoid arthritis and systemic sclerosis. Arthritis Res Ther. 2007;9 Suppl 2:S3. doi: 10.1186/ar2187, PMID 17767741.

Koning GA, Schiffelers RM, Wauben MH, Kok RJ, Mastrobattista E, Molema G, ten Hagen TL, Storm G. Targeting of angiogenic endothelial cells at sites of inflammation by dexamethasone phosphate-containing RGD peptide liposomes inhibits experimental arthritis. Arthritis Rheum. 2006;54(4):1198-208. doi: 10.1002/art.21719, PMID 16575845.

Gaffo A, Saag KG, Curtis JR. Treatment of rheumatoid arthritis. Am J Health Syst Pharm. 2006;63(24):2451-65. doi: 10.2146/ajhp050514, PMID 17158693.

Levick JR. Permeability of rheumatoid and normal human synovium to specific plasma proteins. Arthritis Rheum. 1981;24(12):1550-60. doi: 10.1002/art.1780241215, PMID 7326067.

Levick JR. Microvascular architecture and exchange in synovial joints. Microcirculation. 1995;2(3):217-33. doi: 10.3109/10739689509146768, PMID 8748946.

Levick JR. Hypoxia and acidosis in chronic inflammatory arthritis; relation to vascular supply and dynamic effusion pressure. J Rheumatol. 1990;17(5):579-82. PMID 2359066.

Halin C, Neri D. Antibody-based targeting of angiogenesis. Crit Rev Ther Drug Carrier Syst. 2001;18(3):299-339. doi: 10.1615/CritRevTherDrugCarrierSyst.v18.i3.20, PMID 11442202.

Nagai T, Tanaka M, Tsuneyoshi Y, Matsushita K, Sunahara N, Matsuda T, Yoshida H, Komiya S, Onda M, Matsuyama T. In vitro and in vivo efficacy of a recombinant immunotoxin against folate receptor beta on the activation and proliferation of rheumatoid arthritis synovial cells. Arthritis Rheum. 2006;54(10):3126-34. doi: 10.1002/art.22082, PMID 17009233.

Trachsel E, Bootz F, Silacci M, Kaspar M, Kosmehl H, Neri D. Antibody-mediated delivery of IL-10 inhibits the progression of established collagen-induced arthritis. Arthritis Res Ther. 2007;9(1):R9. doi: 10.1186/ar2115, PMID 17261171.

Taheri A. Nanoparticles of conjugated methotrexate-human serum albumin: preparation and cytotoxicity evaluations. J Nanomaterials 2011;5:1-7. doi: 10.1155/2011/768201

Taheri A, Dinarvand R, Ahadi F, Khorramizadeh MR, Atyabi F. The in vivo antitumor activity of LHRH targeted methotrexate-human serum albumin nanoparticles in 4T1 tumor-bearing Balb/c mice. Int J Pharm. 2012;431(1-2):183-9. doi: 10.1016/j.ijpharm.2012.04.033. PMID 22531853.

Taheri A, Dinarvand R, Atyabi F, Ahadi F, Nouri FS, Ghahremani MH, Ostad SN, Borougeni AT, Mansoori P. Enhanced anti-tumoral activity of methotrexate-human serum albumin conjugated nanoparticles by targeting with luteinizing hormone-releasing hormone (LHRH) peptide. Int J Mol Sci. 2011;12(7):4591-608. doi: 10.3390/ijms12074591, PMID 21845098.

Taheri A, Dinarvand R, Atyabi F, Nouri F, Ahadi F, Ghahremani MH, Ostad SN, Borougeni AT, Mansoori P. Targeted delivery of methotrexate to tumor cells using biotin functionalized methotrexate-human serum albumin conjugated nanoparticles. J Biomed Nanotechnol. 2011;7(6):743-53. doi: 10.1166/jbn.2011.1340, PMID 22416572.

Taheri A, Dinarvand R, Nouri FS, Khorramizadeh MR, Borougeni AT, Mansoori P, Atyabi F. Use of biotin targeted methotrexate-human serum albumin conjugated nanoparticles to enhance methotrexate antitumor efficacy. Int J Nanomed. 2011;6:1863-74. doi: 10.2147/IJN.S23949, PMID 21931482.

Taheri A, Dinarvand R, Atyabi F, Ghahremani MH, Ostad SN. Trastuzumab decorated methotrexate-human serum albumin conjugated nanoparticles for targeted delivery to HER2 positive tumor cells. Eur J Pharm Sci. 2012;47(2):331-40. doi: 10.1016/j.ejps.2012.06.016, PMID 22771547.

Jain S, Mathur R, Das M, Swarnakar NK, Mishra AK. Synthesis, pharmacoscintigraphic evaluation and antitumor efficacy of methotrexate-loaded, folate-conjugated, stealth albumin nanoparticles. Nanomedicine (Lond). 2011;6(10):1733-54. doi: 10.2217/nnm.11.53, PMID 22087800.

Trapani A, Denora N, Iacobellis G, Sitterberg J, Bakowsky U, Kissel T. Methotrexate-loaded chitosan- and glycolchitosan-based nanoparticles: a promising strategy for the administration of the anticancer drug to brain tumors. AAPS PharmSciTech. 2011;12(4):1302-11. doi: 10.1208/s12249-011-9695-x.

Azadi A, Hamidi M, Khoshayand MR, Amini M, Rouini MR. Preparation and optimization of surface-treated methotrexate-loaded nanogels intended for brain delivery. Carbohydrate Polym. 2012;90(1):462-71. doi: 10.1016/j.carbpol.2012.05.066, PMID 24751066.

Ji JG, Wu D, Liu L, Chen J, Xu Y. Preparation, characterization, and in vitro release of folic acid-conjugated chitosan nanoparticles loaded with methotrexate for targeted delivery. Polym Bull. 2012;68(6): 1707-20. doi: 10.1007/s00289-011-0674-x.

Reddy LH, Murthy RR. Influence of polymerization technique and experimental variables on the particle properties and release kinetics of methotrexate from poly(butylcyanoacrylate) nanoparticles. Acta Pharmaceutica. 2004;54(2):103-18. PMID 15274754.

Gao K, Jiang X. Influence of particle size on transport of methotrexate across blood brain barrier by polysorbate 80-coated polybutylcyanoacrylate nanoparticles. Int J Pharm. 2006;310(1-2):213-9. doi: 10.1016/j.ijpharm.2005.11.040, PMID 16426779.

Cascone MG, Lazzeri L, Carmignani C, Zhu Z. Gelatin nanoparticles produced by a simple W/O emulsion as delivery system for methotrexate. J Mater Sci Mater Med. 2002;13(5):523-6. doi: 10.1023/a:1014791327253, PMID 15348607.



How to Cite




Review Article(s)