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Current Bioactive Compounds

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ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Research Article

Quality by Design Approach for Preparation, Characterization, and Statistical Optimization of Naproxen Sodium-loaded Ethosomes via Transdermal Route

Author(s): Ananda Kumar Chettupalli*, Srivani Ajmera, Padmanabha Rao Amarachinta, Ram Mohan Manda and Rajendra Kumar Jadi

Volume 19, Issue 10, 2023

Published on: 07 July, 2023

Article ID: e060623217712 Pages: 20

DOI: 10.2174/1573407219666230606142116

Price: $65

Abstract

Aim: The primary goal of this study is to create a novel naproxen sodium-loaded ethosome drug delivery system for improving bioavailability, solubility and optimize using a statistical approach.

Background: Naproxen sodium (i.e., a non-steroidal anti-inflammatory drug) is chosen as the first line of treatment for rheumatoid arthritis and ankylosing spondylitis. However, naproxen has side effects, such as bronchospasm, an irregular heart rhythm, etc. Therefore, adopting new drug delivery strategies when developing the dosage form is necessary and the need of the hour to prevent its side effects. The available commercial products are administered through the oral and parenteral routes, which lack bioavailability and permeability respectively.

Objective: Novel ethosomal carriers were designed using Box Behnken Design (BBD) and formulation was prepared for enhanced topical delivery of naproxen sodium ethosomal gel.

Methods: In order to analyze the data statistically and graphically with response surface plots, the Box-Behnken design was used to optimize the formulation variables. The independent factors were phosphatidylcholine (X1), cholesterol (X2), and ethanol (X3), while the dependent variables were entrapment efficiency (Y2), vesicle size (Y1), and PDI (Y3). The Carbopol® 940 gel was then made using the improved ethosomes. Its rheological properties, in-vitro release, ex-vivo skin penetration, and deposition were studied.

Results: The best ethosomes were made by mixing phosphatidylcholine and cholesterol in a phosphate buffer at pH 7.4 with 2–5% v/v ethanol. The optimized ethosomes showed a zeta potential of -32.06 ± 0.16 mV, EE of 84.59 ± 2.38%, and a vesicular size of 105 ± 6.97 nm. Compared to the commercial products and the ethanolic solution of naproxen, these ethosomes considerably increased the amount of naproxen permeated through the skin over 24 hours. The stability of the optimized formulation was assessed for three months at room temperature, and it was found that the efficiency of the prepared novel ethosomal formulation remained intact.

Conclusion: In summary, it was discovered that the ethosomal vesicles were potential carriers, showing the improved topical distribution of naproxen sodium. These findings demonstrated that using ethosomes as a transdermal medication carrier for naproxen was feasible. Compared to drug solutions, the ex-vivo permeation and skin deposition experiments produced better results.

Keywords: Naproxen sodium, Ethosomes Box-Behnken design, in vivo studies, non-steroidal anti-inflammatory, entrapment efficiency, transdermal medication.

Graphical Abstract
[1]
Wu, J.H.; Cohen, B.A. The stigma of skin disease. Curr. Opin. Pediatr., 2019, 31(4), 509-514.
[http://dx.doi.org/10.1097/MOP.0000000000000792] [PMID: 31188167]
[2]
Boehncke, W.H.; Boehncke, S.; Schön, M.P. Managing comorbid disease in patients with psoriasis. BMJ, 2010, 340(jan15 1), b5666.
[http://dx.doi.org/10.1136/bmj.b5666] [PMID: 20080817]
[3]
Eyerich, K.; Eyerich, S. Immune response patterns in non-communicable inflammatory skin diseases. J. Eur. Acad. Dermatol. Venereol., 2018, 32(5), 692-703.
[http://dx.doi.org/10.1111/jdv.14673] [PMID: 29114938]
[4]
Leonardi, G.C.; Falzone, L.; Salemi, R.; Zanghì, A.; Spandidos, D.A.; Mccubrey, J.A.; Candido, S.; Libra, M. Cutaneous melanoma: From pathogenesis to therapy. Int. J. Oncol., 2018, 52(4), 1071-1080.
[http://dx.doi.org/10.3892/ijo.2018.4287] [PMID: 29532857]
[5]
Delgado-Charro, M.B.; Guy, R.H. Effective use of transdermal drug delivery in children. Adv. Drug Deliv. Rev., 2014, 73, 63-82.
[http://dx.doi.org/10.1016/j.addr.2013.11.014] [PMID: 24333231]
[6]
Bhowmick, M.; Sengodan, T. Mechanisms, kinetics and mathematical modelling of transdermal permeation-an updated review. Pharm. Glob., 2013, 4(6), 1.
[7]
Horwitz, E.; Pisanty, S.; Czerninski, R.; Helser, M.; Eliav, E.; Touitou, E. A clinical evaluation of a novel liposomal carrier for acyclovir in the topical treatment of recurrent herpes labialis. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod., 1999, 87(6), 700-705.
[http://dx.doi.org/10.1016/S1079-2104(99)70164-2] [PMID: 10397661]
[8]
Dayan, N.; Touitou, E. Carriers for skin delivery of trihexyphenidyl HCl: Ethosomes vs. liposomes. Biomaterials, 2000, 21(18), 1879-1885.
[http://dx.doi.org/10.1016/S0142-9612(00)00063-6] [PMID: 10919691]
[9]
Elsayed, M.M.A.; Abdallah, O.Y.; Naggar, V.F.; Khalafallah, N.M. Lipid vesicles for skin delivery of drugs: Reviewing three decades of research. Int. J. Pharm., 2007, 332(1-2), 1-16.
[http://dx.doi.org/10.1016/j.ijpharm.2006.12.005] [PMID: 17222523]
[10]
Scognamiglio, I.; De Stefano, D.; Campani, V.; Mayol, L.; Carnuccio, R.; Fabbrocini, G.; Ayala, F.; La Rotonda, M.I.; De Rosa, G. Nanocarriers for topical administration of resveratrol: A comparative study. Int. J. Pharm., 2013, 440(2), 179-187.
[http://dx.doi.org/10.1016/j.ijpharm.2012.08.009] [PMID: 22909994]
[11]
Tavakol, S. Toxicity concerns of nanocarriers. In: Nanotechnology-Based Approaches for Targeting and Delivery of Drugs and Genes; Elsevier: Cambridge, MA, 2017; pp. 453-484.
[http://dx.doi.org/10.1016/B978-0-12-809717-5.00016-6]
[12]
Ghanbarzadeh, S.; Arami, S. Enhanced transdermal delivery of diclofenac sodium via conventional liposomes, ethosomes, and transfersomes. BioMed Res. Int., 2013, 2013, 1-7.
[http://dx.doi.org/10.1155/2013/616810] [PMID: 23936825]
[13]
Álvarez-Soria, M.A.; Herrero-Beaumont, G.; Moreno-Rubio, J.; Calvo, E.; Santillana, J.; Egido, J.; Largo, R. Long-term NSAID treatment directly decreases COX-2 and mPGES-1 production in the articular cartilage of patients with osteoarthritis. Osteoarthritis Cartilage, 2008, 16(12), 1484-1493.
[http://dx.doi.org/10.1016/j.joca.2008.04.022] [PMID: 18547825]
[14]
Devi, R.S.; Narayan, S.; Vani, G.; Shyamala Devi, C.S. Gastroprotective effect of Terminalia arjuna bark on diclofenac sodium induced gastric ulcer. Chem. Biol. Interact., 2007, 167(1), 71-83.
[http://dx.doi.org/10.1016/j.cbi.2007.01.011] [PMID: 17327128]
[15]
Li, L.; Rossoni, G.; Sparatore, A.; Lee, L.C.; Del Soldato, P.; Moore, P.K. Anti-inflammatory and gastrointestinal effects of a novel diclofenac derivative. Free Radic. Biol. Med., 2007, 42(5), 706-719.
[http://dx.doi.org/10.1016/j.freeradbiomed.2006.12.011] [PMID: 17291994]
[16]
Piao, H.; Kamiya, N.; Watanabe, J.; Yokoyama, H.; Hirata, A.; Fujii, T.; Shimizu, I.; Ito, S.; Goto, M. Oral delivery of diclofenac sodium using a novel solid-in-oil suspension. Int. J. Pharm., 2006, 313(1-2), 159-162.
[http://dx.doi.org/10.1016/j.ijpharm.2006.02.003] [PMID: 16530362]
[17]
Pawar, P.; Sharma, P.; Chawla, A.; Mehta, R. Formulation and in vitro evaluation of Eudragit S-100 coated naproxen matrix tablets for colon-targeted drug delivery system. J. Adv. Pharm. Technol. Res., 2013, 4(1), 31-41.
[http://dx.doi.org/10.4103/2231-4040.107498] [PMID: 23662280]
[18]
Sean, C.S. Martindale: The Complete Drug Reference; Pharmaceutical Press: Grayslake, IL 60030-7820, USA, , 2005.
[19]
Rahman, Z.; Zidan, A.S.; Habib, M.J.; Khan, M.A. Understanding the quality of protein loaded PLGA nanoparticles variability by Plackett–Burman design. Int. J. Pharm., 2010, 389(1-2), 186-194.
[http://dx.doi.org/10.1016/j.ijpharm.2009.12.040] [PMID: 20038446]
[20]
Purohit, D.; Saini, M.; Pandey, P.; Tripathy, S.; Dureja, H. Implementation of quality by design: A review. Appl. Clin. Res. Clin. Trials Regul. Aff., 2019, 6(2), 99-111.
[http://dx.doi.org/10.2174/2213476X06666190117120029]
[21]
Li, X.; Wang, L.; Wang, B. Optimization of encapsulation efficiency and average particle size of Hohenbuehelia serotina polysaccharides nanoemulsions using response surface methodology. Food Chem., 2017, 229, 479-486.
[http://dx.doi.org/10.1016/j.foodchem.2017.02.051] [PMID: 28372204]
[22]
Tang, S.Y.; Manickam, S.; Wei, T.K.; Nashiru, B. Formulation development and optimization of a novel Cremophore EL-based nanoemulsion using ultrasound cavitation. Ultrason. Sonochem., 2012, 19(2), 330-345.
[http://dx.doi.org/10.1016/j.ultsonch.2011.07.001] [PMID: 21835676]
[23]
Sakdiset, P.; Amnuaikit, T.; Pichayakorn, W.; Pinsuwan, S. Formulation development of ethosomes containing indomethacin for transdermal delivery. J. Drug Deliv. Sci. Technol., 2019, 52, 760-768.
[http://dx.doi.org/10.1016/j.jddst.2019.05.048]
[24]
Qian, C.; McClements, D.J. Formation of nanoemulsions stabilized by model food-grade emulsifiers using high-pressure homogenization: Factors affecting particle size. Food Hydrocoll., 2011, 25(5), 1000-1008.
[http://dx.doi.org/10.1016/j.foodhyd.2010.09.017]
[25]
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]
[26]
Amarachinta, P.R.; Sharma, G.; Samed, N.; Chettupalli, A.K.; Alle, M.; Kim, J-C. Central composite design for the development of carvedilol-loaded transdermal ethosomal hydrogel for extended and enhanced anti-hypertensive effect. J. Nanobiotechnology, 2021, 19(1), 1-15.
[PMID: 33397416]
[27]
Chettupalli, A.K.; Ananthula, M.; Amarachinta, P.R.; Bakshi, V.; Yata, V.K. Design, Formulation, in-vitro and ex-vivo evaluation of atazanavir loaded cubosomal gel. Biointerface Res. Appl. Chem., 2021, 11, 12037-12054.
[28]
Kumar, T.S.; Chettupalli, A.K. Statistically optimized binary ethosomal gel of Carvedilol: Allevialates hypertenstion in male Wistar albino rats. Mol2Ne, 2015, 1, 1-20.
[29]
Bakshi, V.; Amarachinta, P.R.; Chettupalli, A.K. Design, development and optimization of solid lipid nanoparticles of rizatriptan for intranasal delivery: In vitro & in vivo assessment. Mater. Today Proc., 2022, 66, 2342-2357.
[http://dx.doi.org/10.1016/j.matpr.2022.06.329]
[30]
Unnisa, A.; Chettupalli, A.K.; Al Hagbani, T.; Khalid, M.; Jandrajupalli, S.B.; Chandolu, S.; Hussain, T. Development of dapagliflozin solid lipid nanoparticles as a novel carrier for oral delivery: Statistical design, optimization, in-vitro and in-vivo characterization, and evaluation. Pharmaceuticals, 2022, 15(5), 568.
[http://dx.doi.org/10.3390/ph15050568] [PMID: 35631394]
[31]
Zhang, Y.T.; Shen, L.N.; Wu, Z.H.; Zhao, J.H.; Feng, N.P. Comparison of ethosomes and liposomes for skin delivery of psoralen for psoriasis therapy. Int. J. Pharm., 2014, 471(1-2), 449-452.
[http://dx.doi.org/10.1016/j.ijpharm.2014.06.001] [PMID: 24907596]
[32]
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]
[33]
Korsmeyer, R.W.; Gurny, R.; Doelker, E.; Buri, P.; Peppas, N.A. Mechanisms of solute release from porous hydrophilic polymers. Int. J. Pharm., 1983, 15(1), 25-35.
[http://dx.doi.org/10.1016/0378-5173(83)90064-9]
[34]
Hixson, A.W.; Crowell, J.H. Dependence of reaction velocity upon surface and agitation. Ind. Eng. Chem., 1931, 23(8), 923-931.
[35]
Baker, R.W.; Lonsdale, H.K. Controlled release: Mechanisms and rates; Biomed, 1974, pp. 15-71.
[http://dx.doi.org/10.1007/978-1-4684-7239-4_2]
[36]
Esposito, E.; Mariani, P.; Ravani, L.; Contado, C.; Volta, M.; Bido, S.; Drechsler, M.; Mazzoni, S.; Menegatti, E.; Morari, M.; Cortesi, R. Nanoparticulate lipid dispersions for bromocriptine delivery: Characterization and in vivo study. Eur. J. Pharm. Biopharm., 2012, 80(2), 306-314.
[http://dx.doi.org/10.1016/j.ejpb.2011.10.015] [PMID: 22061262]
[37]
Pecora, R. Dynamic light scattering measurement of nanometer particles in liquids. J. Nanopart. Res., 2000, 2(2), 123-131.
[http://dx.doi.org/10.1023/A:1010067107182]
[38]
Barbosa, L.R.S.; Ortore, M.G.; Spinozzi, F.; Mariani, P.; Bernstorff, S.; Itri, R. The importance of protein-protein interactions on the pH-induced conformational changes of bovine serum albumin: a small-angle X-ray scattering study. Biophys. J., 2010, 98(1), 147-157.
[http://dx.doi.org/10.1016/j.bpj.2009.09.056] [PMID: 20085727]
[39]
Jain, S.; Tiwary, A.K.; Sapra, B.; Jain, N.K. Formulation and evaluation of ethosomes for transdermal delivery of lamivudine. AAPS PharmSciTech, 2007, 8(4), 249.
[http://dx.doi.org/10.1208/pt0804111] [PMID: 18181532]
[40]
Sloan, K.B.; Beall, H.D.; Weimar, W.R.; Villanueva, R. The effect of receptor phase composition on the permeability of hairless mouse skin in diffusion cell experiments. Int. J. Pharm., 1991, 73(2), 97-104.
[http://dx.doi.org/10.1016/0378-5173(91)90031-I]
[41]
Combes, R.D.; Gaunt, I.; Balls, M. A scientific and animal welfare assessment of the OECD Health Effects Test Guidelines for the safety testing of chemicals under the European Union REACH system. Altern. Lab. Anim., 2004, 32(3), 163-208.
[http://dx.doi.org/10.1177/026119290403200304] [PMID: 15588165]
[42]
Lee, S.H. Evaluation of acute skin irritation and phototoxicity by aqueous and ethanol fractions of Angelica keiskei. Exp. Ther. Med., 2013, 5(1), 45-50.
[http://dx.doi.org/10.3892/etm.2012.782] [PMID: 23251240]
[43]
Snekhalatha, U.; Anburajan, M.; Venkatraman, B.; Menaka, M. Evaluation of complete Freund’s adjuvant-induced arthritis in a Wistar rat model. Z. Rheumatol., 2013, 72(4), 375-382.
[http://dx.doi.org/10.1007/s00393-012-1083-8] [PMID: 23208192]
[44]
Cong, H.H.; Khaziakhmetova, V.N.; Zigashina, L.E. Rat paw oedema modeling and NSAIDs: Timing of effects. Int. J. Risk Saf. Med., 2015, 27(1), S76.
[45]
Peram, M.R.; Jalalpure, S.; Kumbar, V.; Patil, S.; Joshi, S.; Bhat, K.; Diwan, P. Factorial design based curcumin ethosomal nanocarriers for the skin cancer delivery: In vitro evaluation. J. Liposome Res., 2019, 29(3), 291-311.
[http://dx.doi.org/10.1080/08982104.2018.1556292] [PMID: 30526186]
[46]
Paget, G.E.; Barnes, J.M. Interspecies dosage conversion scheme in evaluation of results and quantitative application in different species. In: Evaluation of Drug Activities; Academic Press: UK, 1964; pp. 160-162.
[47]
Deng, X.; Yin, F.; Lu, X.; Cai, B.; Yin, W. The apoptotic effect of brucine from the seed of Strychnos nux-vomica on human hepatoma cells is mediated via Bcl-2 and Ca2+ involved mitochondrial pathway. Toxicol. Sci., 2006, 91(1), 59-69.
[http://dx.doi.org/10.1093/toxsci/kfj114] [PMID: 16443926]
[48]
Piao, Z.Z.; Lee, E.S.; Tran, H.T.T.; Lee, B.J. Improved analytical validation and pharmacokinetics of valsartan using HPLC with UV detection. Arch. Pharm. Res., 2008, 31(8), 1055-1059.
[http://dx.doi.org/10.1007/s12272-001-1268-4] [PMID: 18787797]
[49]
Ali, M.S.; Alam, M.S.; Alam, N.; Siddiqui, M.R. Preparation, characterization and stability study of dutasteride loaded nanoemulsion for treatment of benign prostatic hypertrophy. Iran. J. Pharm. Res., 2014, 13(4), 1125-1140.
[PMID: 25587300]
[50]
Ghosh, M. Fundamentals of experimental pharmacology. Indian J. Pharmacol., 2007, 39(4), 216.
[51]
Narayanaswamy, R.; Torchilin, V.P. Hydrogels and their applications in targeted drug delivery. Molecules, 2019, 24(3), 603.
[http://dx.doi.org/10.3390/molecules24030603] [PMID: 30744011]
[52]
Ibrahim, H.M.; Ahmed, T.A.; Hussain, M.D.; Rahman, Z.; Samy, A.M.; Kaseem, A.A.; Nutan, M.T.H. Development of meloxicam in situ implant formulation by quality by design principle. Drug Dev. Ind. Pharm., 2014, 40(1), 66-73.
[http://dx.doi.org/10.3109/03639045.2012.746360] [PMID: 23298324]
[53]
Sathyamoorthy, N.; Magharla, D.; Chintamaneni, P.; Vankayalu, S. Optimization of paclitaxel loaded poly (ε-caprolactone) nanoparticles using Box Behnken design. Beni. Suef Univ. J. Basic Appl. Sci., 2017, 6(4), 362-373.
[http://dx.doi.org/10.1016/j.bjbas.2017.06.002]
[54]
Pfeiffer, C.M.; Huff, D.L.; Gunter, E.W. Rapid and accurate HPLC assay for plasma total homocysteine and cysteine in a clinical laboratory setting. Clin. Chem., 1999, 45(2), 290-292.
[http://dx.doi.org/10.1093/clinchem/45.2.290] [PMID: 9931056]
[55]
Nandini, P.T.; Doijad, R.C.; Shivakumar, H.N.; Dandagi, P.M. Formulation and evaluation of gemcitabine-loaded solid lipid nanoparticles. Drug Deliv., 2015, 22(5), 647-651.
[http://dx.doi.org/10.3109/10717544.2013.860502] [PMID: 24283392]
[56]
Dubey, V.; Mishra, D.; Nahar, M.; Jain, V.; Jain, N.K. Enhanced transdermal delivery of an anti-HIV agent via ethanolic liposomes. Nanomedicine., 2010, 6(4), 590-596.
[http://dx.doi.org/10.1016/j.nano.2010.01.002] [PMID: 20093197]
[57]
Zhu, X.; Li, F.; Peng, X.; Zeng, K. Formulation and evaluation of lidocaine base ethosomes for transdermal delivery. Anesthesia. Analgesia., 2013, 117(2), 352-357.
[http://dx.doi.org/10.1213/ANE.0b013e3182937b74]
[58]
Abdulbaqi, I.M.; Darwis, Y.; Khan, N.A.K.; 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]
[59]
Mura, P.; Bragagni, M.; Mennini, N.; Cirri, M.; Maestrelli, F. Development of liposomal and microemulsion formulations for transdermal delivery of clonazepam: Effect of randomly methylated β-cyclodextrin. Int. J. Pharm., 2014, 475(1-2), 306-314.
[http://dx.doi.org/10.1016/j.ijpharm.2014.08.066] [PMID: 25194352]
[60]
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]
[61]
Alalaiwe, A.; Fayed, M.H.; Alshahrani, S.M.; Alsulays, B.B.; Alshetaili, A.S.; Tawfeek, H.M.; Khafagy, E-S. Application of design of experiment approach for investigating the effect of partially pre-gelatinized starch on critical quality attributes of rapid orally disintegrating tablets. J. Drug Deliv. Sci. Technol., 2019, 49, 227-234.
[http://dx.doi.org/10.1016/j.jddst.2018.11.018]
[62]
Mehmood, T.; Ahmed, A.; Ahmad, A.; Ahmad, M.S.; Sandhu, M.A. Optimization of mixed surfactants-based β-carotene nanoemulsions using response surface methodology: An ultrasonic homogenization approach. Food Chem., 2018, 253, 179-184.
[http://dx.doi.org/10.1016/j.foodchem.2018.01.136] [PMID: 29502819]
[63]
Pal, A.; Sunthar, P.; Khakhar, D.V. Effects of ethanol addition on the size distribution of liposome suspensions in water. Ind. Eng. Chem. Res., 2019, 58(18), 7511-7519.
[http://dx.doi.org/10.1021/acs.iecr.8b05028]
[64]
Zu, Y.; Zhang, Y.; Zhao, X.; Shan, C.; Zu, S.; Wang, K.; Li, Y.; Ge, Y. Preparation and characterization of chitosan–polyvinyl alcohol blend hydrogels for the controlled release of nano-insulin. Int. J. Biol. Macromol., 2012, 50(1), 82-87.
[http://dx.doi.org/10.1016/j.ijbiomac.2011.10.006] [PMID: 22020189]
[65]
Shen, Y.; Ling, X.; Jiang, W.; Du, S.; Lu, Y.; Tu, J. Formulation and evaluation of Cyclosporin A emulgel for ocular delivery. Drug Deliv., 2015, 22(7), 911-917.
[http://dx.doi.org/10.3109/10717544.2013.861883] [PMID: 24401095]
[66]
Guilherme, V.A.; Ribeiro, L.N.M.; Alcântara, A.C.S.; Castro, S.R.; Rodrigues da Silva, G.H.; da Silva, C.G.; Breitkreitz, M.C.; Clemente-Napimoga, J.; Macedo, C.G.; Abdalla, H.B.; Bonfante, R.; Cereda, C.M.S.; de Paula, E. Improved efficacy of naproxen-loaded NLC for temporomandibular joint administration. Sci. Rep., 2019, 9(1), 11160.
[http://dx.doi.org/10.1038/s41598-019-47486-w] [PMID: 31371737]
[67]
Su, R.; Fan, W.; Yu, Q.; Dong, X.; Qi, J.; Zhu, Q.; Zhao, W.; Wu, W.; Chen, Z.; Li, Y.; Lu, Y. Size-dependent penetration of nanoemulsions into epidermis and hair follicles: Implications for transdermal delivery and immunization. Oncotarget, 2017, 8(24), 38214-38226.
[http://dx.doi.org/10.18632/oncotarget.17130] [PMID: 28465469]
[68]
Jain, S.K.; Puri, R.; Mahajan, M.; Yadav, S.; Pathak, C.M.; Ganesh, N. Nanovesicular carrier-based formulation for skin cancer targeting: Evaluation of cytotoxicity, intracellular uptake, and preclinical anticancer activity. J. Drug Target., 2015, 23(3), 244-256.
[http://dx.doi.org/10.3109/1061186X.2014.981192] [PMID: 25417933]
[69]
Murugan, C.; Rayappan, K.; Thangam, R.; Bhanumathi, R.; Shanthi, K.; Vivek, R.; Thirumurugan, R.; Bhattacharyya, A.; Sivasubramanian, S.; Gunasekaran, P.; Kannan, S. Combinatorial nanocarrier based drug delivery approach for amalgamation of anti-tumor agents in breast cancer cells: an improved nanomedicine strategy. Sci. Rep., 2016, 6(1), 34053.
[http://dx.doi.org/10.1038/srep34053] [PMID: 28442746]
[70]
Ma, Y.; Li, Z.; Wang, Y.; Feng, J. Brucine induces the apoptosis of U266 multiple myeloma cells by phosphorylation of c-Jun. Mol. Med. Rep., 2013, 7(2), 481-484.
[http://dx.doi.org/10.3892/mmr.2012.1194] [PMID: 23175437]
[71]
Jain, S.; Patel, N.; Madan, P.; Lin, S. Quality by design approach for formulation, evaluation and statistical optimization of diclofenac-loaded ethosomes via transdermal route. Pharm. Dev. Technol., 2015, 20(4), 473-489.
[http://dx.doi.org/10.3109/10837450.2014.882939] [PMID: 24490793]

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