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Drug Delivery Letters

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ISSN (Print): 2210-3031
ISSN (Online): 2210-304X

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Research Article

A Novel Natural Polymers Based Nanoparticles Gel Formulation for the Treatment of Rheumatoid Arthritis: Optimization and In-vivo Evaluation

Author(s): Sushma Chaudhary, Manjul Pratap Singh, Chandana Venkateaswara Rao and Ajay Kumar Singh Rawat*

Volume 11, Issue 2, 2021

Published on: 19 February, 2021

Page: [164 - 178] Pages: 15

DOI: 10.2174/2210303111666210219152401

Price: $65

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Abstract

Background: In 1988, the US Food and Drug Administration permitted low dose methotrexate for the treatment of rheumatoid arthritis that would change the progression of the disease. Methotrexate is a folic acid antagonist and its systemic use causes numerous side effects; including hepatic toxicity. It would be preferable to deliver methotrexate by the topical route to reduce side-effects along with ease of administration and reduced dosing frequency. So, nanoparticle gel is a hopeful approach to treat rheumatoid arthritis.

Objective: The study aims to develop a nanoparticles gel containing novel natural polymer-based methotrexate nanoparticles and evaluate its therapeutic potential on Complete Freund’s Adjuvant– Induced Arthritis rat model and compare it to methotrexate and dexamethasone gel.

Materials and Methods: The five batches of methotrexate nanoparticles gel were prepared viz. F1W2, F2W2, F3W2, F4W2 and methotrexate gel for the topical application by using different concentrations of Carbopol 934 base and characterized for their evaluation parameters: homogeneity, grittiness, pH, spread-ability, viscosity determination, and drug content studies. The arthritic potential of methotrexate-nanoparticles gel was evaluated by Complete Freund’s Adjuvant–Induced Arthritis rats model based on percent inhibition oedema and arthritic score.

Result and Discussion: Methotrexate nanoparticles gel significantly reduced the percentage inhibition of oedema compared to methotrexate and dexamethasone gel. The therapeutic activity of nanoparticles gel was found to be F3W2 ≥ F2W2 ≥ F1W2 ≥ F4W2 ≥ MTX gel. So, the optimized nanoparticle gel formulation F3W2 can be effective in the treatment of rheumatoid arthritis.

Conclusion: The developed novel nanoparticles gel formulation can be a promising alternative to existing methotrexate and dexamethasone gel.

Keywords: Carbopol 934, chitosan, Hibiscus cannabinus mucilage, methotrexate, nanoparticle gel, rheumatoid arthritis.

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Graphical Abstract

[1]
Kaur, A.; Kumar, S.L.H. Controlled drug delivery approaches for rheumatoid arthritis. J. Appl. Pharm. Sci., 2012, 2(8), 21-32.
[http://dx.doi.org/10.7324/JAPS.2012.2803]
[2]
Afeltra, A. Treatment of rheumatoid arthritis: new therapeutic approaches with biological agents. Curr. Drug Targets Immune Endocr. Metabol. Disord., 2001, 1(1), 45-65.
[http://dx.doi.org/10.2174/1568008013341677] [PMID: 12476781]
[3]
Arend, W.P.; Dayer, J.M. Cytokine antagonist and rheumatoid arthritis. J. Arthritis Rheumatoid, 1990, 33, 305-315.
[http://dx.doi.org/10.1002/art.1780330302]
[4]
Pharm, C.T. Nano Therapeutic Approaches for the Treatment of Rheumatoid Arthritis. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 2011, 3(1), 109-110.
[5]
Krause, M.L.; Makol, A. Management of rheumatoid arthritis during pregnancy: challenges and solutions. Open Access Rheumatol., 2016, 8, 23-36.
[PMID: 27843367]
[6]
Badger, A.M.; Lee, J.C. Advances in anti-arthritic therapeutics. Drug Discov. Today, 1997, 2, 427-435.
[http://dx.doi.org/10.1016/S1359-6446(97)01098-2]
[7]
Weinblatt, M.E. Methotrexate: who would have predicted its importance in rheumatoid arthritis? Arthritis Res. Ther., 2018, 20(1), 103.
[http://dx.doi.org/10.1186/s13075-018-1599-7] [PMID: 29848356]
[8]
Avasatthi, V.; Pawar, H. Dora. C.P.; Bansod P.; Singh G.M.; Sarasija S.; A novel nanogel formulation of methotrexate for topical treatment of psoriasis: optimization, in vitro and in vivo evaluation. Pharm. Dev. Technol., 2015, 1(9), 1-7.
[9]
Prasada, R. Koul.V.; Ananda S.; and Kharc R. K.; Transdermal Iontophoretic Delivery of Methotrexate: Physicochemical Considerations. Trends Biomater. Artif. Organs, 2005, 18(2), 187-190.
[10]
Alvarez-Figueroa, M.J.; Blanco-Méndez, J. Transdermal delivery of methotrexate: iontophoretic delivery from hydrogels and passive delivery from microemulsions. Int. J. Pharm., 2001, 215(1-2), 57-65.
[http://dx.doi.org/10.1016/S0378-5173(00)00674-8] [PMID: 11250092]
[11]
Rajendra, P.; Thireesha, B. UV spectrophotometric method development and validation for the determination of lornoxicam in microspnges. Int. J. Appl. Pharm., 2018, 10(1), 1-5.
[12]
Chaudhary, S.; Singh, M.P.; Rawat, A.K.S. Qualitative and quantitative gas chromatography-mass spectroscopy analysis and characterization of naturally isolated mucilage in Hibiscus cannabinus L. (Malvaceae). J. Tropical Plant Res., 2019, 6(1), 101-105.
[http://dx.doi.org/10.22271/tpr.2019.v6.i1.014]
[13]
Seetharaman, S.; Balya, H.; Kuppusamy, G. Preparation and evaluation of cefixime nanoparticles prepared using fenugreek seed mucilage and chitosan as natural polymers. Int. J. Pharma. Clin. Res., 2016, 8(3), 179-188.
[14]
Sharma, H.K.; Lahkar, S.; Kanta Nath, L. Formulation and in vitro evaluation of metformin hydrochloride loaded microspheres prepared with polysaccharide extracted from natural sources. Acta Pharm., 2013, 63(2), 209-222.
[http://dx.doi.org/10.2478/acph-2013-0019] [PMID: 23846143]
[15]
Douglas, K.L.; Tabrizian, M. Effect of experimental parameters on the formation of alginate-chitosan nanoparticles and evaluation of their potential application as DNA carrier. J. Biomater. Sci. Polym. Ed., 2005, 16(1), 43-56.
[http://dx.doi.org/10.1163/1568562052843339] [PMID: 15796304]
[16]
Daisy Chella, S.K.; Tharani, C.B.; Narayanan, N.; Senthil, K.C. Formulation and characterization of methotrexate loaded sodium alginate chitosan nanoparticles. Ind. J. Res. Pharma. Biotechnol., 2013, 1(6), 915-922.
[17]
Abitha, M.H.; Mathew, F. Formulation and evaluation of nanoparticles as sustained release topical formulation containing non-steroidal anti- inflammatory drug. World J. Clin. Pharmacol, Microbiol. Toxicol., 2015, 1(3), 35-42.
[18]
Sailaja, K.; Swati, A.P. Preparation of sodium alginate nanoparticles by desolvation technique using iso propyl alcohol as desolvating agent. Int. J. adv. Pharm., 2015, 4(5), 60-71.
[19]
Gupta, V.K.; Karar, P.K. Optimization of process variables for the preparation of chitosan alginate nanoparticles. Int. J. Pharm. Pharm. Sci., 2011, 3(2), 7880.
[20]
Ahmed Mohammed, N.; Ahmed, R.G.; Momdouh, M. Formulation and in-vitro evaluation of pantoprazole loaded PH sensitive polymeric nanoparticles. Future. J. Pharm. Sci., 2017, 3(1), 1-15.
[21]
Gomathi, T.; Govindarajan, C.; Rose H R, M.H.; Sudha, P.N.; Imran, P.K.; Venkatesan, J.; Kim, S.K. Studies on drug-polymer interaction, in vitro release and cytotoxicity from chitosan particles excipient. Int. J. Pharm., 2014, 468(1-2), 214-222.
[http://dx.doi.org/10.1016/j.ijpharm.2014.04.026] [PMID: 24742716]
[22]
Sanna, V.; Roggio, A.M.; Siliani, S.; Piccinini, M.; Marceddu, S.; Mariani, A.; Sechi, M. Development of novel cationic chitosan-and anionic alginate-coated poly(D,L-lactide-co-glycolide) nanoparticles for controlled release and light protection of resveratrol. Int. J. Nanomedicine, 2012, 7, 5501-5516.
[PMID: 23093904]
[23]
Krishna, S.; Swati, A.P. Preparation of sodium alginate nanoparticles by desolvation technique using iso propyl alcohol as desolvating agent. Int. J. adv. Harm., 2015, 4(5), 60-71.
[24]
Mahobia, S.; Bajpai, J.; Bajpai, A.K. An In-vitro Investigation of Swelling Controlled Delivery of Insulin from Egg Albumin Nanocarriers. Iran. J. Pharm. Res., 2016, 15(4), 695-711.
[PMID: 28243266]
[25]
Chaudhary, S.; Singh, M.P.; Srivastava, M.; Rawat, A.K.S. Functional properties for formulation development in mucilage of deccan hemp (Java jute). Trop. Plant Res., 2019, 6(1), 129-132.
[26]
Xie, S.; Zhu, L.; Dong, Z.; Wang, Y.; Wang, X.; Zhou, W. Preparation and evaluation of ofloxacin-loaded palmitic acid solid lipid nanoparticles. Int. J. Nanomed., 2011, 6, 547-555.
[PMID: 21468357]
[27]
Lehr, C.M.; Bouwstra, J.A.; Schacht, E.; Junginger, H.E. In-vitro evaluation of mucoadhesive properties of chitosan and some other natural polymers. Int. J. Pharm., 1992, 78, 43-48.
[http://dx.doi.org/10.1016/0378-5173(92)90353-4]
[28]
Maia, C.S.; Mehnert, W.; Schäfer-Korting, M. Solid lipid nanoparticles as drug carriers for topical glucocorticoids. Int. J. Pharm., 2000, 196(2), 165-167.
[http://dx.doi.org/10.1016/S0378-5173(99)00413-5] [PMID: 10699710]
[29]
Jana, S.; Manna, S.; Nayak, A.K.; Sen, K.K.; Basu, S.K. Carbopol gel containing chitosan-egg albumin nanoparticles for transdermal aceclofenac delivery. Colloids Surf. B Biointerfaces, 2014, 114, 36-44.
[http://dx.doi.org/10.1016/j.colsurfb.2013.09.045] [PMID: 24161504]
[30]
Kaur, L.P.; Garg, R.; Gupta, G.D. Development and evaluation of topical gel of minoxidil from different polymer bases in application of alopecia. Int. J. Pharm. Pharm. Sci., 2010, 2, 43-47.
[31]
Kaur, J.; Srinivasan, K.K.; Joseph, A.; Gupta, A.; Singh, Y.; Srinivas, K.S.; Jain, G. Development and validation of stability indicating method for the quantitative determination of venlafaxine hydrochloride in extended release formulation using high performance liquid chromatography. J. Pharm. Bioallied Sci., 2010, 2(1), 22-26.
[http://dx.doi.org/10.4103/0975-7406.62701] [PMID: 21814426]
[32]
Barry, B.W.; Meyer, M.C. The rheological properties of Carbopol gels: continuous shear and creep properties of Carbopol gels. Int. J. Pharm., 1979, 2, 1-25.
[http://dx.doi.org/10.1016/0378-5173(79)90025-5]
[33]
Enkelejda, G.; Entela, H.; Skerdilaid, X.; Ledjan, M. Formulation and in vitro evaluation of diclofenac sodium gel. Int. J. Pharm. Pharm. Sci., 2014, 6, 259-261.
[34]
Tamizhrasi, S.; Shukla, A.; Shivkumar, T.; Rathi, V.; Rathi, J.C. Formulation and evaluation of lamivudine loaded polymethacrylic acid nanoparticles. Int. J. Pharm. Tech. Res., 2009, 1(3), 411-415.
[35]
Amresh, G.; Singh, P.N.; Rao, ChV.; Singh, P.N. Antinociceptive and antiarthritic activity of Cissampelos pareira roots. J. Ethnopharmacol., 2007, 111(3), 531-536.
[http://dx.doi.org/10.1016/j.jep.2006.12.026] [PMID: 17240096]
[36]
Suchita, M.; Dixit, P.K. In-vivo anti-inflammatory and anti-arthritic activity of ethanolic extract of Asparagus racemosus roots. Int. Res. J. Pharm, 2013, 4(4), 167-172.
[37]
Chandel, H.S.; Singh, S.; Kushwaha, R. Evaluation of anti-arthritic activity on Luffa echinaa Roxb. Fruits on rats. Asian J. Biomed. Pharmaceut.Sci., 2013, 3(21), 36-41.
[38]
Mali, S.M.; Sinnathambi, A.; Kapase, C.U.; Bodhankar, S.L.; Mahadik, K.R. Anti-arthritic activity of standardised extract of Phyllanthus amarus in Freund’s complete adjuvant induced arthritis. Biomed. Aging Pathol., 2011, 1, 185-190.
[http://dx.doi.org/10.1016/j.biomag.2011.09.004]
[39]
Otari, K.V.; Shete, R.V.; Upasani, C.D.; Adak, V.S.; Bagade, M.Y.; Harpalani, A.N. Evaluation of Anti-inflammatory and anti-arthritic activities of ethanolic extract of Vernonia anthelmintica seeds. J. Cell Tissue Res., 2010, 10(2), 2269-2280.
[40]
Padmanabha pillai, N.; Ramaswamy, S.; Gopalakrishnan, V.; Ghosh, M.N.; Effect of cholinergic drugs on acute and chronic morphine dependence. Int. de. Pharmacodynamic. et de Therapie, 1982, 257, 147-154.
[41]
Bajpai, A.K.; Likhitkar, S. Investigation of magnetically enhanced swelling behaviour of Superparamagnetic starch nanoparticles. Bull. Mater. Sci., 2013, 36, 15-24.
[http://dx.doi.org/10.1007/s12034-013-0432-9]
[42]
Kalpana, D.H. Fabrication and Characterization of Chitosan Nanoparticles: A Controlled Release Approach to Words Tuberculosis Chemotherapy. Drug Deliv. Lett., 2018, 8(3), 209-215.
[http://dx.doi.org/10.2174/2210303108666180803142516]
[43]
Dwivedi, P. Shaswat K.; Sharma M.; Shukla R.; Verma A.; Shukla P.; Tripathi P.; Gupta P.; Saini D.; Khandelwal K.; Verma R.; Dwivedi A.K.; and Mishra. P.R.;. Exploiting 4- sulphate N-acetyl galactosamine decorated gelatin nanoparticles for effective targeting to professional phagocytes in- vitro and in- vivo. J. Drug Target., 2012, 1-14.
[44]
Bonferoni, M.C.; Rossi, S.; Ferrari, F.; Caramella, C. A modified Franz diffusion cell for simultaneous assessment of drug release and washability of mucoadhesive gels. Pharm. Dev. Technol., 1999, 4(1), 45-53.
[http://dx.doi.org/10.1080/10837459908984223] [PMID: 10027212]
[45]
Bachhav, Y.G.; Patravale, V.B. Microemulsion based vaginal gel of fluconazole: formulation, in vitro and in vivo evaluation. Int. J. Pharm., 2009, 365(1-2), 175-179.
[http://dx.doi.org/10.1016/j.ijpharm.2008.08.021] [PMID: 18790032]
[46]
El Laithy, H.M.; El-Shaboury, K.M. The development of Cutina lipogels and gel microemulsion for topical administration of fluconazole. AAPS. Pharm. Sci. Tech., 2002, 3(4), E35.
[PMID: 12916929]
[47]
Mufassir, M.; Zahid, Z.; Rana Z., N.J.; Sangshetti, Z.Z. Polymeric nanoparticle encapsulating Docetaxel for prolonged and targeted delivery to breast cancer. J. Innovat. Pharmaceut. Biol. Sci., 2017, 4, 132-140.
[48]
Jain, A.; Jain, S.K. In vitro and cell uptake studies for targeting of ligand anchored nanoparticles for colon tumors. Eur. J. Pharm. Sci., 2008, 35(5), 404-416.
[http://dx.doi.org/10.1016/j.ejps.2008.08.008] [PMID: 18824095]

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