Abstract
The physicochemical properties of the optimized microemulsion and the permeating ability of oxyresveratrol in microemulsion were evaluated, and the efficacy of oxyresveratrol microemulsion in cutaneous herpes simplex virus type 1 (HSV-1) infection in mice was examined. The optimized microemulsion was composed of 10% w/w of isopropyl myristate, 35% w/w of Tween 80, 35% w/w of isopropyl alcohol, and 20% w/w of water. The mean particle diameter was 9.67 ± 0.58 nm, and the solubility of oxyresveratrol in the microemulsion was 196.34 ± 0.80 mg/ml. After accelerated and long-term stability testing, the microemulsion base and oxyresveratrol-loaded microemulsion were stable. The cumulative amount of oxyresveratrol permeating through shed snake skin from microemulsion at 6 h was 93.04 times compared to that of oxyresveratrol from Vaseline, determined at 20% w/w concentration. In cutaneous HSV-1 infection in mice, oxyresveratrol microemulsion at 20%, 25%, and 30% w/w, topically applied five times daily for 7 days after infection, was significantly effective in delaying the development of skin lesions and protecting from death (p < 0.05) compared with the untreated control. Oxyresveratrol microemulsion at 25% and 30% w/w was significantly more effective than that of 30% w/w of oxyresveratrol in Vaseline (p < 0.05) and was as effective as 5% w/w of acyclovir cream, topically applied five times daily (p > 0.05). These results demonstrated that topical oxyresveratrol microemulsion at 20–30% w/w was suitable for cutaneous HSV-1 mouse infection.
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REFERENCES
Naesens L, De Clercq E. Recent developments in herpesvirus therapy. Herpes. 2001;8(1):12–6.
Whitley R, Roizman B. Herpes simplex virus infections. Lancet. 2001;357:1513–8. doi:10.1016/S0140-6736(00)04638-9.
De Clercq E. Antiviral drugs in current clinical use. J Clin Virol. 2004;30:115–33. doi:/10.1016/j.jcv.2004.02.009.
Fatahzadeh M, Schwartz RA. Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis and management. J Am Acad Dermatol. 2007;57(5):737–63.
Greco A, Diaz JJ, Thouvenot D, Morfin F. Novel targets for the development of anti- herpes compounds. Infect Disord Drug Targets. 2007;7(1):11–8.
Balfour HH. Antiviral drugs. N Engl J Med. 1999;340(16):1255–68.
Zhu W, Yu A, Wang W, Dong R, Wu J, Zhai G. Formulation design of microemulsion for dermal delivery of penciclovir. Int J Pharm. 2008;360(1–2):184–90. doi:10.1016/j.ijpharm.2008.04.008.
Shishu, Rajan S, Kamalpreet. Development of novel microemulsion-based topical formulations of acyclovir for the treatment of cutaneous herpetic infections. AAPS Pharm Sci Tech. 2009;10(2):559–65. doi:10.1208/s12249-009-9242-1.
Treister NS, Woo SB. Topical n-docosanol for management of recurrent herpes labialis. Expert Opin Pharmacother. 2010;11(5):853–60.
Sritularak B, De-Eknamkul W, Likhitwitayawuid K. Tyrosinase inhibitors form Artocarpus lakoocha. Thai J Pharm Sci. 1998;22:149–55.
Likhitwitayawuid K, Sritularak B, Benchanak K, Lipipun V, Mathew J, Schinaz RF. Phenolics with antiviral activity from Millettia erythrocalyx and Artocarpus lakoocha. Nat Prod Res. 2005;19:177–82.
Chuanasa T, Phromjai J, Lipipun V, Likhitwitayawuid K, Suzuki M, Pramyothin P, Hattori M, Shiraki K. Anti-herpes simplex virus (HSV-1) activity of oxyresveratrol derived from Thai medicinal plant: mechanism of action and therapeutic efficacy on cutaneous HSV-1 infection in mice. Antiviral Res. 2008;80(1):62–70. doi:10.1016/j.antiviral.2008.05.002.
Lipipun V, Sasivimolphan P, Yoshida Y, Daikoku T, Sritularak B, Ritthidej G, Likhitwitayawuid K, Pramyothin P, Hattori M, Shiraki K. Topical cream-based oxyresveratrol in the treatment of cutaneous HSV-1 infection in mice. Antiviral Res. 2011;91(2):154–60. doi:10.1016/j.antiviral.2011.05.013.
Sasivimolphan P, Lipipun V, Likhitwitayawuid K, Takemoto M, Pramyothin P, Hattori M, Shiraki K. Inhibitory activity of oxyresveratrol on wild-type and drug-resistant varicella-zoster virus replication in vitro. Antiviral Res. 2009;84(1):95–7. doi:10.1016/j.antiviral.2009.07.010.
Kim YM, Yun J, Lee CK, Lee H, Min KR, Kim Y. Oxyresveratrol and hydroxystilbene compounds: inhibitory effect on tyrosinase and mechanism of action. J Biol Chem. 2002;227(18):16340–4. doi:10.1074/jbc.M200678200.
Lorenz P, Roychowdhury S, Engelmann M, Wolf G, Horn TFW. Oxyresveratrol and resveratrol are potent antioxidants and free radical scavengers: effect on nitrosative and oxidative stress derived form microglial cells. Nitric Oxide. 2003;9:64–76. doi:10.1016/j.niox.2003.09.005.DOI:dx.doi.org.
Saowakon N, Tansatit T, Wanichanon C, Chaakul W, Reutrakul V, Sobhan P. Fasciola gigantica: anthelmintic effect of the aqueous extract of Artocarpus lakoocha. Exp Parasitol. 2009;122(4):289–98.
Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery system. Adv Drug Deliv Rev. 2000;45:89–121.
Santos P, Watkinson AC, Hadgraft J, Lane ME. Application of microemulsions in dermal and transdermal drug delivery. Skin Pharmacol Physiol. 2008;21:246–59. doi:10.1159/000140228.
Azeem A, Khan ZI, Aqil M, Ahmad FJ, Khar RK, Talegaonkar S. Microemulsions as a surrogate carrier for dermal drug delivery. Drug Dev Ind Pharm. 2009;35(5):525–47. doi:10.1080/03639040802448646.
Shiraki K, Rapp F. Effects of caffeine on herpes simplex virus. Intervirology. 1988;29:235–40.
Kurokawa M, Ochiai H, Nagasaka K, Neki M, Xu H, Kadota S, Sutardjo S, Matsumoto T, Namba T, Shiraki K. Antiviral traditional medicines against herpes simplex virus (HSV-1), poliovirus, and measles virus and their therapeutic efficacies for HSV-1 infection in mice. Antiviral Res. 1993;22(2–3):175–88.
Lipipun V, Kurokawa M, Suttisri R, Taweechotipatr P, Pramyothin P, Hattori M, Shiraki K. Efficacy of Thai medicinal plant extracts against herpes simplex virus type 1 infection in vitro and in vivo. Antiviral Res. 2003;60(3):175–80. doi:10.1016S0166-3542(03)00152-9.
Kuehl PJ, Stratton SP, Powell MB, Myrdal PB. Preformulation, formulation, and in vivo efficacy of topically applied apomine. Int J Pharm. 2009;382(1–2):104–10. doi:10.1016/j.ijpharm.2009.08.016.
Huang YB, Lin YH, Lu TM, Wang RJ, Tsai YH, Wu PC. Transdermal delivery of capsaicin derivative-sodium nonivamide acetate using microemulsions as vehicles. Int J Pharm. 2008;349(1–2):206–11.
Derle DV, Sagar BSH, Pimpale R. Microemulsion as a vehicle for transdermal permeation of nimesulide. Indian J Pharm Sci. 2006;68:622–5. doi:10.4103/0250-474X.29630.
Boonme P, Krauel K, Graf A, Rades T, Junyaprasert VB. Characterization of microemulsion structure in the pseudoternary phase diagram of isopropyl palmitate/water/brij 97:1-butanol. AAPS Pharm Sci Tech. 2005;7(2):E1–6.
Djordjevic L, Primorac M, Stupar M. In vitro release of diclofenac diethylamine from caprylocaproyl macrogolglycerides based microemulsions. Int J Pharm. 2005;296:73–9. doi:/10.1016/j.ijpharm.2005.02.014.
Bali V, Ali M, Ali J. Nanocarrier for the enhanced bioavailability of a cardiovascular agent: in vitro, pharmacodynamic, pharmacokinetic and stability assessment. Int J Pharm. 2001;403(1–2):46–56. doi:10.1016/j.ijpharm.2010.10.018.
Chao J, Yu MS, Wang M, Chang RCC. Dietary oxyresveratrol prevents parkinsonian mimetic 6-hydroxydopamine neurotoxicity. Free Radic Biol Med. 2008;45(7):1019–26. doi:10.1016/j.freeradbiomed.2008.07.002.
Itoh T, Xia J, Magavi R, Nishihata T, Rytting H. Use of shed snake skin as a model membrane for in vitro percutaneous penetration studies: comparison with human skin. Pharm Res. 1990;7(10):1042–7.
Chandra A, Sharma PK, Irchhiaya R. Microemulsion-based hydrogel formulation for transdermal delivery of dexamethasone. Asian J Pharm. 2009;3(1):30–6. doi:10.4103/0973-8398.49172.
Kawakami K, Yoshikawa T, Moroto Y, Kanahashi K, Nishihara Y, Masuda K. Microemulsion formulation for enhanced absorption of poorly soluble drug. I. Prescription design. J Contr Release. 2002;81(1–2):65–74. doi:10.1016/S0168-3659(02)00049-4.
Kogan A, Garti N. Microemulsions as transdermal drug delivery vehicles. Ad Coll Interf Sci. 2006;123–126:369–85.
Tsai YH, Chang JT, Chang JS, Huang CT, Huang YB, Wu PC. The effect of component of microemulsions on transdermal delivery of buspirone hydrochloride. J Pharm Sci. 2011;100(6):2358–65. doi:10.1002/jps.22474.
Joshi M, Patravale V. Formulation and evaluation of nanostructured lipid carrier (NLC-based gel of valdecoxib. Drug Dev Ind Pharm. 2006;32(8):911–8. doi:10.1016/j.ijpharm.2007.05.060.
Hashem FM, Shaker DS, Ghorab MK, Nasr M, Ismail A. Formation, characterization, and clinical evaluation of microemulsion containing clotrimazole for topical delivery. AAPS Pharm Sci Tech. 2011;12(3):879–86. doi:10.1208/s12249-011-9653-7.
Hwang SR, Lim SJ, Park JS, Kim CK. Phospholipid-based microemulsion formulation of all-trans-retinoic acid for parenteral administration. Int J Pharm. 2004;276(1–2):175–83. doi:10.1016/j.ijpharm.2004.02.025.
Park KM, Kim CK. Preparation and evaluation of flurbiprofen-loaded microemulsion for parenteral delivery. Int J Pharm. 1999;181(2):173–9. doi:10.1016/S0378-5173(99)00029-0.
Baboota S, Alam S, Sharma S, Sahni JK, Kumar A, Ali J. Nanocarrier-based hydrogel of betamethasone dipropionate and salicylic acid for treatment of psoriasis. Int J Pharma Investig. 2011;1(3):139–47. doi:10.4103/2230- 973X.85963.
Baroli B, Lopez-Quintela MA, Delgado-Charro MB, Fadda AM, Blanco-Mendez J. Microemulsions for topical delivery of 8-methoxsalen. J Contr Release. 2000;69(1):209–18. doi:10.1016/S0168-3659(00)00309-6.
Rodriguez-Bonilla P, Lopez-Nicolas JM, Garcia-Carmona F. Use of reversed phase high pressure liquid chromatographyl for the physicochemical and thermodynamic characterization of oxyresveratrol/β-cyclodextrin complexes. J Chromatorgr B Anal Technol Biomed Life Sci. 2010;878(19):1569–75. doi:10.1016/j.jchromb.2010.04.016.
Mei ZN, Chen HB, Weng T, Yang YJ, Yang XL. Solid lipid nanoparticle and microemulsion for topical delivery of triptolide. Eur J Pharm Biopharm. 2003;56:189–96. doi:10.1016/S0939-6411(03)00067-5.
Imanidis G, Hartner KC, Mazer NA. Intestinal permeation and metabolism of a model peptide (leuprolide) and mechanisms of permeation enhancement by non-ionic surfactants. Int J Pharm. 1995;120(1):41–50. doi:0378-5173(94)00407-V.
Chen H, Chang X, Weng T, Zhao X, Gao Z, Yang Y, Xu H, Yang X. A study of microemulsion systems for transdermal delivery of triptolide. J Contr Release. 2004;98(3):427–36. doi:10.1016/j.jconrel.2004.06.001.
Zhao X, Liu JP, Zhang X, Li Y. Enhancement of transdermal delivery of theophylline using microemulsion vehicle. Int J Pharm. 2006;327(1–2):58–64. doi:10.1016/j.ijpharm.2006.07.027.
Rigg PC, Barry BW. Shed snake skin and hairless mouse skin as model membranes for human skin during permeation studies. J Invest Dermatol. 1990;94:235–40.
Harada K, Murakami T, Kawasaki E, Higashi Y, Yamamoto S, Yata N. In vitro permeability to salicylic acid of human, rodent and shed snake skin. J Pharm Pharmacol. 1993;4:414–8.
Takahash K, Tamagawa S, Katagi T, Rytting JH, Nishihata T, Mizuno N. Percutaneous penetration of basic compounds through shed snake skin as a model membrane. J Pharm Pharmacol. 1993;45:882–6.
Pope LE, Marcelletti JF, Katz LR, Lin JY, Katz DH, Parish ML, Spear PG. The anti- herpes simplex virus activity of n-docosanol includes inhibition of the viral entry process. Antivir Res. 1998;40(1–2):85–94. doi:org/10.1016/S0166-3542(98)00048-5.
ACKNOWLEDGMENTS
We gratefully thank the Japan Society for the Promotion of Science 2009, University of Toyama, Chulalongkorn University Centenary Academic Development Project (2008–2009) and Chulalongkorn University Graduate Scholarship Commemorating the 72nd Anniversary of His Majesty King (2008–2010) for the support of this work. We thank Tomoko Okuda for her excellent assistance.
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Sasivimolphan, P., Lipipun, V., Ritthidej, G. et al. Microemulsion-Based Oxyresveratrol for Topical Treatment of Herpes Simplex Virus (HSV) Infection: Physicochemical Properties and Efficacy in Cutaneous HSV-1 Infection in Mice. AAPS PharmSciTech 13, 1266–1275 (2012). https://doi.org/10.1208/s12249-012-9828-x
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DOI: https://doi.org/10.1208/s12249-012-9828-x