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Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Exploration of Nanoethosomal Transgel of Naproxen Sodium for the Treatment of Arthritis

Author(s): Farzana Anjum, Foziyah Zakir, Devina Verma, Mohd Aqil, Manvi Singh, Pooja Jain, Mohd Aamir Mirza, Md. Khalid Anwer and Zeenat Iqbal*

Volume 17, Issue 10, 2020

Page: [885 - 897] Pages: 13

DOI: 10.2174/1567201817666200724170203

Price: $65

Abstract

Background: The present work aimed to develop an ethosomal gel of naproxen sodium for the amelioration of rheumatoid arthritis.

Objective: In the present work, we have explored the potential of ethosomes to deliver naproxen into deeper skin strata. Further, the anti-inflammatory efficacy of naproxen ethosomal formulation was assessed using the carrageenan-induced rat paw edema model.

Methods: Naproxen sodium nanoethosomes were prepared using different proportions of lipoid S100 (50mg-200mg), ethanol (20-50%) and water, and were further characterized on the basis of vesicle morphology, entrapment efficiency, zeta potential, in-vitro drug release and ex-vivo permeation studies.

Results: The optimized ethosomal formulation was found to have 129 ± 0.01 nm particle size, 0.295 Polydispersity Index (PDI), -3.29 mV zeta potential, 88% entrapment efficiency and 96.573% drug release in 24 hours. TEM and SEM analysis of the optimized formulation showed slightly smooth spherical structures. The Confocal laser scanning microscopy showed that ethosomes could easily infiltrate into deeper dermal layers (upto 104.9μm) whereas the hydroalcoholic solution of the drug could penetrate up to 74.9μm. Further, the optimized ethosomal formulation was incorporated into 1% carbopol 934 gel base and optimized wherein the transdermal flux was found to be approximately 10 times more than the hydroethanolic solution. Also, the in-vivo pharmacodynamic study of the optimized ethosomal gel exhibited a higher percentage inhibition of swelling paw edema than marketed diclofenac gel.

Conclusion: The ethosomal gel was successfully developed and has shown the potential to be a good option for the replacement of conventional therapies of rheumatoid arthritis.

Keywords: Arthritis, cutaneous delivery, ethosome gel, naproxen sodium, penetration, skin permeation.

Graphical Abstract
[1]
Berenbaum, F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthri Cartil, 2013, 21(1), 16-21.
[http://dx.doi.org/10.1016/j.joca.2012.11.012 ] [PMID: 23194896]
[2]
Karlson, E.W.; Deane, K. Environmental and gene-environment interactions and risk of rheumatoid arthritis. Rheum. Dis. Clin. North Am., 2012, 38(2), 405-426.
[http://dx.doi.org/10.1016/j.rdc.2012.04.002 ] [PMID: 22819092]
[3]
McInnes, I.B.; Schett, G. The pathogenesis of rheumatoid arthritis. N. Engl. J. Med., 2011, 365(23), 2205-2219.
[http://dx.doi.org/10.1056/NEJMra1004965 ] [PMID: 22150039]
[4]
Rajurkar, V.G.; Tambe, A.B.; Deshmukh, V.K. Topical anti-Inflammatory gels of naproxen entrapped in eudragit based microsponge delivery system. J. Adv. Chem. Eng., 2015, 5, 1-6.
[5]
Dubey, V.; Mishra, D.; Jain, N.K. Melatonin loaded ethanolic liposomes: physicochemical characterization and enhanced transdermal delivery. Eur. J. Pharm. Biopharm., 2007, 67(2), 398-405.
[http://dx.doi.org/10.1016/j.ejpb.2007.03.007 ] [PMID: 17452098]
[6]
Lane, M.E. Skin penetration enhancers. Int. J. Pharm., 2013, 447(1-2), 12-21.
[http://dx.doi.org/10.1016/j.ijpharm.2013.02.040 ] [PMID: 23462366]
[7]
Stoicea, N.; Fiorda-Diaz, J.; Joseph, N.; Shabsigh, M.; Arias-Morales, C.; Gonzalez-Zacarias, A.A.; Mavarez-Martinez, A.; Marjoribanks, S.; Bergese, S.D. Advanced analgesic drug delivery and nanobiotechnology. Drugs, 2017, 77(10), 1069-1076.
[http://dx.doi.org/10.1007/s40265-017-0744-y ] [PMID: 28470586]
[8]
Szura, D.; Ozimek, Ł.; Przybyło, M.; Karłowicz-Bodalska, K.; Jaźwińska-Tarnawska, E.; Wiela-Hojeńska, A.; Han, S. The impact of liposomes on transdermal permeation of naproxen--in vitro studies. Acta Pol. Pharm., 2014, 71(1), 145-151.
[PMID: 24779203]
[9]
Ustündağ Okur, N.; Apaydın, S.; Karabay Yavaşoğlu, N.Ü.; Yavaşoğlu, A.; Karasulu, H.Y. Evaluation of skin permeation and anti-inflammatory and analgesic effects of new naproxen microemulsion formulations. Int. J. Pharm., 2011, 416(1), 136-144.
[PMID: 21723930]
[10]
Tian, Q.; Ren, F.; Xu, Z.; Xie, Y.; Zhang, S. Preparation of high solubilizable microemulsion of naproxen and its solubilization mechanism. Int. J. Pharm., 2012, 426(1-2), 202-210.
[http://dx.doi.org/10.1016/j.ijpharm.2012.01.019 ] [PMID: 22274589]
[11]
Touitou, E.; Godin, B.; Weis, C. Enhanced delivery of drugs into and across the skin by ethosomal carriers. Drug Dev. Res., 2000, 50, 406-415.
[http://dx.doi.org/10.1002/1098-2299(200007/08)50:3/4<406::AID DDR23>3.0.CO;2-M]
[12]
Sharma, G.; Goyal, H.; Thakur, K.; Raza, K.; Katare, O.P. Novel Elastic Membrane Vesicles (EMVs) and ethosomes-mediated effective topical delivery of aceclofenac: a new therapeutic approach for pain and inflammation. Drug Deliv., 2016, 23(8), 3135-3145.
[http://dx.doi.org/10.3109/10717544.2016.1155244 ] [PMID: 26960815]
[13]
Esposito, E.; Drechsler, M.; Huang, N.; Pavoni, G.; Cortesi, R.; Santonocito, D.; Puglia, C. Ethosomes and organogels for cutaneous administration of crocin. Biomed. Microdevices, 2016, 18(6), 108.
[http://dx.doi.org/10.1007/s10544-016-0134-3 ] [PMID: 27830454]
[14]
Zhang, Y.; Ng, W.; Feng, X.; Cao, F.; Xu, H. Lipid vesicular nanocarrier: quick encapsulation efficiency determination and transcutaneous application. Int. J. Pharm., 2017, 516(1-2), 225-230.
[http://dx.doi.org/10.1016/j.ijpharm.2016.11.011 ] [PMID: 27832955]
[15]
Zakir, F.; Vaidya, B.; Goyal, A.K.; Malik, B.; Vyas, S.P. Development and characterization of oleic acid vesicles for the topical delivery of fluconazole. Drug Deliv., 2010, 17(4), 238-248.
[http://dx.doi.org/10.3109/10717541003680981 ] [PMID: 20235758]
[16]
Shaji, J.; Menon, I. PEGylated liposomes of meloxicam: optimization by quality by design, in vitro characterization and cytotoxicity evaluation. Pharm. Nanotechnol., 2017, 5(2), 119-137.
[http://dx.doi.org/10.2174/2211738505666170428152129 ] [PMID: 28462699]
[17]
Iizhar, S.A.; Syed, I.A.; Satar, R.; Ansari, S.A. In vitro assessment of pharmaceutical potential of ethosomes entrapped with terbinafine hydrochloride. J. Adv. Res., 2016, 7(3), 453-461.
[http://dx.doi.org/10.1016/j.jare.2016.03.003 ] [PMID: 27222750]
[18]
Verma, S.; Bhardwaj, A.; Vij, M.; Bajpai, P.; Goutam, N.; Kumar, L. Oleic acid vesicles: a new approach for topical delivery of antifungal agent. Artif. Cells Nanomed. Biotechnol., 2014, 42(2), 95-101.
[http://dx.doi.org/10.3109/21691401.2013.794351 ] [PMID: 23656670]
[19]
Hardiansyah, A.; Yang, M.C.; Liu, T.Y.; Kuo, C.Y.; Huang, L.Y.; Chan, T.Y. Hydrophobic drug-loaded PEGylated magnetic liposomes for drug-controlled release. Nanoscale Res. Lett., 2017, 12(1), 355.
[http://dx.doi.org/10.1186/s11671-017-2119-4 ] [PMID: 28525950]
[20]
Bashir, S.; Teo, Y.Y.; Naeem, S.; Ramesh, S.; Ramesh, K. pH responsive N-succinyl chitosan/Poly (acrylamide-co-acrylic acid) hydrogels and in vitro release of 5-fluorouracil. PLoS One, 2017, 12(7), e0179250.
[http://dx.doi.org/10.1371/journal.pone.0179250 ] [PMID: 28678803]
[21]
Negi, P.; Aggarwal, M.; Sharma, G.; Rathore, C.; Sharma, G.; Singh, B.; Katare, O.P. Niosome-based hydrogel of resveratrol for topical applications: an effective therapy for pain related disorder(s). Biomed. Pharmacother., 2017, 88, 480-487.
[http://dx.doi.org/10.1016/j.biopha.2017.01.083 ] [PMID: 28126673]
[22]
Burchacka, E.; Potaczek, P.; Paduszyński, P.; Karłowicz-Bodalska, K.; Han, T.; Han, S. New effective azelaic acid liposomal gel formulation of enhanced pharmaceutical bioavailability. Biomed. Pharmacother., 2016, 83, 771-775.
[http://dx.doi.org/10.1016/j.biopha.2016.07.014 ] [PMID: 27484346]
[23]
Gupta, N.K.; Dixit, V.K. Development and evaluation of vesicular system for curcumin delivery. Arch. Dermatol. Res., 2011, 303(2), 89-101.
[http://dx.doi.org/10.1007/s00403-010-1096-6 ] [PMID: 21085975]
[24]
Abdulbaqi, I.M.; Darwis, Y.; Khan, N.A.; Assi, R.A.; Khan, A.A. Ethosomal nanocarriers: the impact of constituents and formulation techniques on ethosomal properties, in vivo studies, and clinical trials. Int. J. Nanomedicine, 2016, 11, 2279-2304.
[http://dx.doi.org/10.2147/IJN.S105016 ] [PMID: 27307730]
[25]
Radwan, S.A.A.; ElMeshad, A.N.; Shoukri, R.A. Microemulsion loaded hydrogel as a promising vehicle for dermal delivery of the antifungal sertaconazole: design, optimization and ex vivo evaluation. Drug Dev. Ind. Pharm., 2017, 43(8), 1351-1365.
[http://dx.doi.org/10.1080/03639045.2017.1318899 ] [PMID: 28420288]
[26]
Yang, L.; Wu, L.; Wu, D.; Shi, D.; Wang, T.; Zhu, X. Mechanism of transdermal permeation promotion of lipophilic drugs by ethosomes. Int. J. Nanomedicine, 2017, 12, 3357-3364.
[http://dx.doi.org/10.2147/IJN.S134708 ] [PMID: 28490875]
[27]
Nguyen, T.K.; Im, K.H.; Choi, J.; Shin, P.G.; Lee, T.S. Evaluation of antioxidant, anti-cholinesterase, and anti-inflammatory effects of culinary mushroom Pleurotus pulmonarius. Mycobiology, 2016, 44(4), 291-301.
[http://dx.doi.org/10.5941/MYCO.2016.44.4.291 ] [PMID: 28154487]
[28]
Rédei, D.; Kúsz, N.; Jedlinszki, N.; Blazsó, G.; Zupkó, I.; Hohmann, J. Bioactivity-guided investigation of the anti-inflammatory activity of Hippophae rhamnoides fruits. Planta Med., 2018, 84(1), 26-33.
[http://dx.doi.org/10.1055/s-0043-114424 ] [PMID: 28662529]
[29]
Kalavathy, H.M.; Regupathi, I.; Pillai, M.G.; Miranda, L.R. Modelling, analysis and optimization of adsorption parameters for H3PO4 activated rubber wood sawdust using Response Surface Methodology (RSM). Colloids Surf. B Biointerfaces, 2009, 70(1), 35-45.
[http://dx.doi.org/10.1016/j.colsurfb.2008.12.007 ] [PMID: 19155164]
[30]
Muthukumar, M.; Mohan, D.; Rajendran, M. Optimization of mix proportions of mineral aggregates using Box Behnken design of experiments, cement concrete compos. Cement Concr. Compos., 2003, 25, 751-758.
[http://dx.doi.org/10.1016/S0958-9465(02)00116-6]
[31]
Prasad, P.S.; Imam, S.S.; Aqil, M.; Sultana, Y.; Ali, A. QbD-based carbopol transgel formulation: characterization, pharmacokinetic assessment and therapeutic efficacy in diabetes. Drug Deliv., 2016, 23(3), 1057-1066.
[http://dx.doi.org/10.3109/10717544.2014.936536 ] [PMID: 25033041]
[32]
Imam, S.S.; Aqil, M.; Akhtar, M.; Sultana, Y.; Ali, A. Formulation by design-based proniosome for accentuated transdermal delivery of risperidone: in vitro characterization and in vivo pharmacokinetic study. Drug Deliv., 2015, 22(8), 1059-1070.
[http://dx.doi.org/10.3109/10717544.2013.870260 ] [PMID: 24471715]
[33]
Qumbar, M. Ameeduzzafar; Imam, S.S.; Ali, J.; Ahmad, J.; Ali, A. Formulation and optimization of lacidipine loaded niosomal gel for transdermal delivery: In-vitro characterization and in-vivo activity. Biomed. Pharmacother., 2017, 93, 255-266.
[http://dx.doi.org/10.1016/j.biopha.2017.06.043 ] [PMID: 28738502]
[34]
Ruckmani, K.; Sankar, V. Formulation and optimization of Zidovudine niosomes. AAPS PharmSciTech, 2010, 11(3), 1119-1127.
[http://dx.doi.org/10.1208/s12249-010-9480-2 ] [PMID: 20635228]
[35]
Limsuwan, T.; Boonme, P.; Khongkow, P.; Amnuaikit, T. Ethosomes of phenylethyl resorcinol as vesicular delivery system for skin lightening applications. BioMed Res. Int., 2017, 2017, 8310979.
[http://dx.doi.org/10.1155/2017/8310979 ] [PMID: 28804723]
[36]
Tiwari, R.; Tiwari, G.; Wal, P. Development, characterization and transdermal delivery of dapsone and an antibiotic entrapped in ethanolic liposomal gel for the treatment of lapromatous leprosy. Open Nanomed. J., 2018, 5, 1-15.
[http://dx.doi.org/10.2174/1875933501805010001]
[37]
Gao, X.; Wang, B.; Wei, X.; Rao, W.; Ai, F.; Zhao, F.; Men, K.; Yang, B.; Liu, X.; Huang, M.; Gou, M.; Qian, Z.; Huang, N.; Wei, Y. Preparation, characterization and application of star-shaped PCL/PEG micelles for the delivery of doxorubicin in the treatment of colon cancer. Int. J. Nanomedicine, 2013, 8, 971-982.
[http://dx.doi.org/10.2147/IJN.S39532 ] [PMID: 23493403]
[38]
Cojocaru, V.; Ranetti, A.E.; Hinescu, L.G. Formulation and evaluation of in vitro release kinetics of Na3CaDTPA decorporation agent embedded in microemulsion-based gel formulation for topical delivery. Farmacia, 2015, 63, 656-664.
[39]
Caddeo, C.; Sales, O.D.; Valenti, D.; Saurí, A.R.; Fadda, A.M.; Manconi, M. Inhibition of skin inflammation in mice by diclofenac in vesicular carriers: liposomes, ethosomes and PEVs. Int. J. Pharm., 2013, 443(1-2), 128-136.
[http://dx.doi.org/10.1016/j.ijpharm.2012.12.041 ] [PMID: 23299087]
[40]
Limsuwan, T.; Amnuaikit, T. Development of ethosomes containing mycophenolic acid. Procedia Chem., 2012, 4, 328-335.
[http://dx.doi.org/10.1016/j.proche.2012.06.046]
[41]
Ahad, A.; Al-Saleh, A.A.; Al-Mohizea, A.M.; Al-Jenoobi, F.I.; Raish, M.; Yassin, A.E.B.; Alam, M.A. Formulation and characterization of phospholipon 90 G and tween 80 based transfersomes for transdermal delivery of eprosartan mesylate. Pharm. Dev. Technol., 2018, 23(8), 787-793.
[http://dx.doi.org/10.1080/10837450.2017.1330345 ] [PMID: 28504046]
[42]
Faisal, W.; Soliman, G.M.; Hamdan, A.M. Enhanced skin deposition and delivery of voriconazole using ethosomal preparations. J. Liposome Res., 2018, 28(1), 14-21.
[http://dx.doi.org/10.1080/08982104.2016.1239636 ] [PMID: 27667097]
[43]
Babaie, S.; Ghanbarzadeh, S.; Davaran, S.; Kouhsoltani, M.; Hamishehkar, H. Nanoethosomes for dermal delivery of Lidocaine. Adv. Pharm. Bull., 2015, 5(4), 549-556.
[http://dx.doi.org/10.15171/apb.2015.074 ] [PMID: 26819928]
[44]
Zidan, A.S.; Mokhtar Ibrahim, M.; Megrab, N.A.E. Optimization of methotrexate loaded niosomes by Box-Behnken design: an understanding of solvent effect and formulation variability. Drug Dev. Ind. Pharm., 2017, 43(9), 1450-1459.
[http://dx.doi.org/10.1080/03639045.2017.1318907 ] [PMID: 28420295]
[45]
AbdelSamie, S.M.; Kamel, A.O.; Sammour, O.A.; Ibrahim, S.M. Terbinafine hydrochloride nanovesicular gel: in vitro characterization, ex vivo permeation and clinical investigation. Eur. J. Pharm. Sci., 2016, 88, 91-100.
[http://dx.doi.org/10.1016/j.ejps.2016.04.004 ] [PMID: 27072432]
[46]
Ly, H.V.; Longo, M.L. The influence of short-chain alcohols on interfacial tension, mechanical properties, area/molecule, and permeability of fluid lipid bilayers. Biophys. J., 2004, 87(2), 1013-1033.
[http://dx.doi.org/10.1529/biophysj.103.034280 ] [PMID: 15298907]
[47]
Abdel Messih, H.A.; Ishak, R.A.; Geneidi, A.S.; Mansour, S. Nanoethosomes for transdermal delivery of tropisetron HCl: multi-factorial predictive modeling, characterization, and ex vivo skin permeation. Drug Dev. Ind. Pharm., 2017, 43(6), 958-971.
[http://dx.doi.org/10.1080/03639045.2017.1287717 ] [PMID: 28121196]
[48]
Essa, E.A. Effect of formulation and processing variables on the particle size of sorbitan monopalmitate niosomes. Asian. J. Pharm. (Cairo), 2010, 4, 227-233.
[49]
Fathalla, D.; Soliman, G.; Fouad, E. Development and in vitro/in vivo evaluation of liposomal gels for the sustained ocular delivery of latanoprost. J. Clin. Exp. Ophthalmol., 2015, 6, 390.
[50]
Shen, L.N.; Zhang, Y.T.; Wang, Q.; Xu, L.; Feng, N.P. Enhanced in vitro and in vivo skin deposition of apigenin delivered using ethosomes. Int. J. Pharm., 2014, 460(1-2), 280-288.
[http://dx.doi.org/10.1016/j.ijpharm.2013.11.017 ] [PMID: 24269286]
[51]
Rakesh, R.; Anoop, K.R. Formulation and optimization of nano-sized ethosomes for enhanced transdermal delivery of cromolyn sodium. J. Pharm. Bioallied Sci., 2012, 4(4), 333-340.
[http://dx.doi.org/10.4103/0975-7406.103274 ] [PMID: 23248569]
[52]
Verma, P.; Pathak, K. Nanosized ethanolic vesicles loaded with econazole nitrate for the treatment of deep fungal infections through topical gel formulation. Nanomedicine (Lond.), 2012, 8(4), 489-496.
[http://dx.doi.org/10.1016/j.nano.2011.07.004 ] [PMID: 21839053]
[53]
Ghanbarzadeh, S.; Arami, S. Enhanced transdermal delivery of diclofenac sodium via conventional liposomes, ethosomes, and transfersomes. BioMed Res. Int., 2013, 2013, 616810.
[http://dx.doi.org/10.1155/2013/616810 ] [PMID: 23936825]
[54]
Çelik, B.; Özdemir, S.; Barla Demirkoz, A.; Üner, M. Optimization of piribedil mucoadhesive tablets for efficient therapy of Parkinson’s disease: physical characterization and ex vivo drug permeation through buccal mucosa. Drug Dev. Ind. Pharm., 2017, 43(11), 1836-1845.
[http://dx.doi.org/10.1080/03639045.2017.1349785 ] [PMID: 28665152]
[55]
Zhai, Y.; Xu, R.; Wang, Y.; Liu, J.; Wang, Z.; Zhai, G. Ethosomes for skin delivery of ropivacaine: preparation, characterization and ex vivo penetration properties. J. Liposome Res., 2015, 25(4), 316-324.
[http://dx.doi.org/10.3109/08982104.2014.999686 ] [PMID: 25625544]
[56]
Thomas, L.; Zakir, F.; Mirza, M.A.; Anwer, M.K.; Ahmad, F.J.; Iqbal, Z. Development of curcumin loaded chitosan polymer based nanoemulsion gel: in vitro, ex vivo evaluation and in vivo wound healing studies. Int. J. Biol. Macromol., 2017, 101, 569-579.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.03.066 ] [PMID: 28322948]
[57]
Yadav, N.K.; Nanda, S.; Sharma, G.; Katare, O.P. Systematically optimized ketoprofen-loaded novel proniosomal formulation for periodontitis: in vitro characterization and in vivo pharmacodynamic evaluation. AAPS PharmSciTech, 2017, 18(5), 1863-1880.
[http://dx.doi.org/10.1208/s12249-016-0665-1 ] [PMID: 27844417]
[58]
Niu, X.Q.; Zhang, D.P.; Bian, Q.; Feng, X.F.; Li, H.; Rao, Y.F.; Shen, Y.M.; Geng, F.N.; Yuan, A.R.; Ying, X.Y.; Gao, J.Q. Mechanism investigation of ethosomes transdermal permeation. Int. J. Pharm. X, 2019, 1, 100027.
[http://dx.doi.org/10.1016/j.ijpx.2019.100027 ] [PMID: 31517292]

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