The Preliminary Study of Methotrexate Encapsulated Reverse Micelles preparation for Psoriasis Treatment.

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Pathomthat Srisuk
Seangrawee Sutoarinyanan
Padungkwan Chitropas
Watcharee Khunkitti

Abstract

Introduction: Methotrexate (MTX) is commonly used in severe psoriasis treatment but major side effects such as hepatoxicity and bone marrow suppression are mainly limited its use. To avoid these problems, localized topical delivery has been initiated to prepare using a reverse micelle system (RMs) that consisted of sodium bis (ethyl hexyl) sulfosuccinate (AOT) as a surfactant, n-hexane as a solvent, glutaraldehyde (GTA) as a crosslinking agent, and chitosan (CS) as core-shell. Methods: The aim of the study is to investigate the effect of different molecular weights (MWs) of CS on the physical properties; mean diameter, zeta potential, and MTX encapsulation efficiency (%EE). All RMs formulations were physically characterized by dynamic light scattering (DLS) and UV-Vis spectroscopy. Results: Results reveal that the mean diameter of the prepared RMs with different MWs of CS was in averaged range of 400-900 nm. The zeta potential and %EE were approximately -60 to -30 mV and 90%. In view of the experiment, the MWs of CS is a major parameter affecting to the mean diameter of RMs. In contrary, CaCl2 has the smallest effect on the particle size of RMs. Conclusion: High encapsulation of MTX in RMs can suggest that further develop to be a potential carrier in topical delivery system and MTX loaded RMs might reduce its side effects and improves its therapeutic efficacy in the treatment of psoriasis. 

Article Details

Section
Pharmaceutical Sciences

References

Banerjee T, Mitra S, Kumar SA, Kumar SR, Maitra A. Preparation, characterization and biodistribution of ultrafine chitosan nanoparticles. Int J Pharm 2002; 243(1–2): 93-105.

Bayliffe AI, Brigandi RA, Wilkins HJ, Levick MP. Emerging therapeutic targets in psoriasis. Curr Opin Pharmacol 2004; 4(3): 306-310.

Bharali DJ, Sahoo SK, Mozumdar S, Maitra A. Cross-linked polyvinylpyrrolidone nanoparticles: a potential carrier for hydrophilic drugs. J Colloid Interface Sci 2003; 258(2): 415-423.

Cambón A, Rey-Rico A, Mistry D, et al. Doxorubicin-loaded micelles of reverse poly(butylene oxide)–poly(ethylene oxide)–poly(butylene oxide) block copolymers as efficient “active” chemotherapeutic agents. Int J Pharm 2013; 445(1–2): 47-57.

Elder JT, Bruce AT, Gudjonsson JE, et al. Molecular Dissection of Psoriasis: Integrating Genetics and Biology. J Invest Dermatol 2010; 130(5): 1213-1226.

Eskicirak B, Zemheri E, Cerkezoglu A. The treatment of psoriasis vulgaris: 1% topical methotrexate gel. Int J Dermatol 2006; 45(8): 965-969.

Frank CS, Alan MM. Methotrexate and psoriasis in the era of new biologic agents. J. Am. Acad. Dermatol 2004; 50: 301-309.

Gallardo V, Morales ME, Ruiz MA, Delgado AV. An experimental investigation of the stability of ethylcellulose latex: Correlation between zeta potential and sedimentation. Eur J Pharma Sci 2005; 26(2): 170-175.

Jones MC, Gao H, Leroux JC. Reverse polymeric micelles for pharmaceutical applications. J Control Release 2008; 132(3): 208-215.

Kafshgari M, Khorram M, Mansouri M, Samimi A, Osfouri S. Preparation of alginate and chitosan nanoparticles using a new reverse micellar system. Iran Polym J 2012; 21(2): 99-107.

Kouchak, M, Avadi M, Abbaspour M, Jahangiri A, Boldaji SK. Effect of different molecular weights of chitosan on preparation and Characterization of Insulin loaded Nanoparticles by Ion Gelation Method. Int. J. Drug Dev. & Res 2012; 4(2): 271-277.

Kreilgaard M. Influence of microemulsions on cutaneous drug delivery. Adv Drug Deliv Rev 2002; 54 Supp0: 77-98.

Kumar MNVR, Muzzarelli RAA, Muzzarelli C, Sashiwa H, Domb AJ. Chitosan Chemistry and Pharmaceutical Perspectives. Chem Rev 2004; 104(12): 6017-6084.

Lebwohl M, Ali S. Treatment of psoriasis. Part 2. Systemic therapies. J Am Acad Dermatol 2001; 45(5): 649-664.

Lee WR, Shen SC, Fang CL, Zhuo RZ, Fang JY. Topical delivery of methotrexate via skin pretreated with physical enhancement techniques: low-fluence erbium:YAG laser and electroporation. Lasers Sur Med 2008; 40(7): 468-476.

Li YY, Chen XG, Liu CS, et al. Effect of the Molecular Mass and Degree of Substitution of Oleoylchitosan on the Structure, Rheological Properties, and Formation of Nanoparticles. J Agric Food Chem 2007; 55(12): 4842-4847.

Linden KG, Weinstein GD. Psoriasis: current perspectives with an emphasis on treatment. Am J Med 1999; 107(6): 595-605.

Müller-Goymann CC. Physicochemical characterization of colloidal drug delivery systems such as reverse micelles, vesicles, liquid crystals and nanoparticles for topical administration. Eur J Pharm Biopharm 2004; 58(2): 343-356.

Onoue S, Yamada S, Chan HK. Nanodrugs: pharmacokinetics and safety. Int J Nanomedicine 2014; 9: 1025-1037.

Rodriguez C, Lowery L, Scamehorn J, Harwell J. Kinetics of precipitation of surfactants. I. Anionic surfactants with calcium and with cationic surfactants. J Surfactants Deterg 2001; 4(1): 1-14.

Singka GSL, Samah NA, Zulfakar MH, Yurdasiper A, Heard CM. Enhanced topical delivery and anti-inflammatory activity of methotrexate from an activated nanogel. Eur J Pharm Biopharm 2010; 76(2): 275-281.

Sonia TA. and Sharma C. (2011). Chitosan and Its Derivatives for Drug Delivery Perspective. Chitosan for Biomaterials I. R. Jayakumar, M. Prabaharan and R. A. A. Muzzarelli, Springer Berlin Heidelberg. 243: 23-53.

Srisuk P, Thongnopnua P, Raktanonchai U, Kanokpanont S. Physico-chemical characteristics of methotrexate-entrapped oleic acid-containing deformable liposomes for in vitro transepidermal delivery targeting psoriasis treatment. Int J Pharm 2012; 427(2): 426-434.

Lim ST, Martin GP, Brown MB. In vivo and in vitro characterization of novel microparticulates based on hyaluronan and chitosan hydroglutamate. AAPS PharmsciTech 2001; 2(4): article 20.

Trotta M, Peira E, Carlotti ME, Gallarate M. Deformable liposomes for dermal administration of methotrexate. Int J Pharm 2004; 270(1–2): 119-125.

Thi Bich TN, Suming L, André D. Reverse micelles prepared from amphiphilic polylactide--poly (ethylene glycol) block copolymers for controlled release of hydrophilic drugs. Int J Pharm 2015; 495(1): 154-161.

Tsoi LC, Spain SL, Knight J, et al. Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity.Nat Genet 2012; 44(12): 1341-1348.

Vila A, Sánchez A, Janes K, Behrens I, Kissel T, Jato JLV, Alonso MAJ. Low molecular weight chitosan nanoparticles as new carriers for nasal vaccine delivery in mice. Eur J Pharm Biopharm 2004; 57(1): 123-131.

Wong TW, Zhao YL, Sen A, Hui SW. Pilot study of topical delivery of methotrexate by electroporation. Br J Dermatol 2005; 152(3): 524-530.

Yang HC, Hon MH. The effect of the molecular weight of chitosan nanoparticles and its application on drug delivery. Microchem J 2009; 92(1): 87-91.

Zingaretti L, Mariano CN, Boscatto L, Chiacchiera SM, Durantini EN, Bertolotti SG, Rivarola CR, Silber JJ. Distribution of amines in water/AOT/n-hexane reverse micelles: influence of the amine chemical structure." J Colloid Interface Sci 2005; 286(1): 245-252.