PDF herunterladen
Planta Med 2013; 79(02): 131-136
DOI: 10.1055/s-0032-1328058
Pharmacokinetic Investigations
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Evaluation of Percutaneous Absorption of Esculetin: Effect of Chemical Enhancers

Sergio del Rio Sancho
1   Instituto de Ciencias Biomédicas, Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, Valencia, Spain
,
César Eulogio Serna Jiménez
1   Instituto de Ciencias Biomédicas, Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, Valencia, Spain
,
María Aracely Calatayud Pascual
1   Instituto de Ciencias Biomédicas, Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, Valencia, Spain
,
Cristina Balaguer Fernández
1   Instituto de Ciencias Biomédicas, Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, Valencia, Spain
,
Andrés Femenía Font
1   Instituto de Ciencias Biomédicas, Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, Valencia, Spain
,
Encarna Castillo García
1   Instituto de Ciencias Biomédicas, Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, Valencia, Spain
,
Virginia Merino
2   Centro de Reconocimiento Molecular y Desarrollo Tecnológico, Centro Mixto Universidad Politécnica de Valencia – Universidad de Valencia, Departamento de Farmacia y Tecnología Farmacéutica, Universidad de Valencia, Valencia, Spain
,
Alicia López Castellano
1   Instituto de Ciencias Biomédicas, Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, Valencia, Spain
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 19. September 2012
revised 06. November 2012

accepted 09. November 2012

Publikationsdatum:
18. Dezember 2012 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

Percutaneous transdermal absorption of esculetin (6,7-dihydroxycoumarin), an oxidative damage inhibitor, was evaluated by means of in vitro permeation studies in which vertical Franz-type diffusion cells and pig ear skin were employed. To determine the absorption of esculetin, we validated a simple, accurate, precise, and rapid HPLC-UV method. Additionally, the effects of several percutaneous enhancers were studied. Pretreatment of porcine skin was performed with ethanol (control vehicle), decenoic acid, oleic acid, R-(+)-limonene, and laurocapram (Azone®) (5 % in ethanol, w/w, respectively). Pretreatment of skin with oleic acid or laurocapram led to statistically significant differences in the transdermal flux of esculetin with respect to controls. Of the two enhancers, laurocapram showed the greatest capacity to enhance the flux of esculetin across pig skin.

Key words

esculetin - absorption enhancer - in vitro model - transdermal drug delivery
 

  • References

  • 1 Chang WS, Lin CC, Chuang SC, Chiang HC. Superoxide anion scavenging effect of coumarins. Am J Chin Med 1996; 24: 11-17
    CrossrefPubMedSuche in Google Scholar
  • 2 Masamoto Y, Ando H, Murata Y, Shimoishi Y, Tada M, Takahata K. Mushroom tyrosinase inhibitory activity of esculetin isolated from seeds of Euphorbia lathyris L. Biosci Biotechnol Biochem 2003; 67: 631-634
    CrossrefPubMedSuche in Google Scholar
  • 3 Neichi T, Koshihara Y, Murota S. Inhibitory effect of esculetin on 5-lipoxygenase and leukotriene biosynthesis. Biochim Biophys Acta 1983; 753: 130-132
    CrossrefPubMedSuche in Google Scholar
  • 4 Egan D, OʼKennedy R, Moran E, Cox D, Prosser E, Thornes RD. The pharmacology, metabolism, analysis, and applications of coumarin and coumarin-related compounds. Drug Metab Rev 1990; 22: 503-529
    CrossrefPubMedSuche in Google Scholar
  • 5 Schimmer O, Eschelbach H. Esculetin in Alchemilla speciosa: identification and antimutagenic properties. Pharmazie 1997; 52: 476-478
    PubMedSuche in Google Scholar
  • 6 Martín-Aragón S, Benedi JM, Villar AM. Effects of the antioxidant (6,7-dihydroxycoumarin) esculetin on the glutathione system and lipid peroxidation in mice. Gerontology 1998; 44: 21-25
    CrossrefPubMedSuche in Google Scholar
  • 7 Lin WL, Wang CJ, Tsai YY, Liu CL, Hwang JM, Tseng TH. Inhibitory effect of esculetin on oxidative damage induced by t-butyl hydroperoxide in rat liver. Arch Toxicol 2000; 74: 467-472
    CrossrefPubMedSuche in Google Scholar
  • 8 Elliott S, Rowan AD, Carrere S, Koshy P, Catterall JB, Cawston TE. Esculetin inhibits cartilage resorption induced by interleukin 1alpha in combination with oncostatin M. Ann Rheum Dis 2001; 60: 158-165
    CrossrefPubMedSuche in Google Scholar
  • 9 Matsunaga K, Yoshimi N, Yamada Y, Shimizu M, Kawabata K, Ozawa Y, Hara A, Mori H. Inhibitory effects of nabumetone, a cyclooxygenase-2 inhibitor, and esculetin, a lipoxygenase inhibitor, on N-methyl-N-nitrosourea-induced mammary carcinogenesis in rats. Jpn J Cancer Res 1998; 89: 496-501
    CrossrefPubMedSuche in Google Scholar
  • 10 Noguchi M, Kitagawa H, Miyazaki I, Mizukami Y. Influence of esculetin on incidence, proliferation, and cell kinetics of mammary carcinomas induced by 7,12-dimethylbenz[a]anthracene in rats on high- and low-fat diets. Jpn J Cancer Res 1993; 84: 1010-1014
    CrossrefPubMedSuche in Google Scholar
  • 11 Yang J, Xiao YL, He XR, Qiu GF, Hu XM. Aesculetin-induced apoptosis through a ROS-mediated mitochondrial dysfunction pathway in human cervical cancer cells. J Asian Nat Prod Res 2010; 12: 185-193
    CrossrefPubMedSuche in Google Scholar
  • 12 Park C, Jin CY, Kim GY, Choi IW, Kwon TK, Choi BT, Lee SJ, Lee WH, Choi YH. Induction of apoptosis by esculetin in human leukemia U937 cells through activation of JNK and ERK. Toxicol Appl Pharmacol 2008; 227: 219-228
    CrossrefPubMedSuche in Google Scholar
  • 13 Yang JY, Della-Fera MA, Hartzell DL, Nelson-Dooley C, Hausman DB, Baile CA. Esculetin induces apoptosis and inhibits adipogenesis in 3 T3-L1 cells. Obesity 2006; 14: 1691-1699
    CrossrefPubMedSuche in Google Scholar
  • 14 Kaneko T, Tahara S, Takabayashi F. Suppression of lipid hydroperoxide-induced oxidative damage to cellular DNA by esculetin. Biol Pharm Bull 2003; 26: 840-844
    CrossrefPubMedSuche in Google Scholar
  • 15 Tahara S, Baba N, Matsuo M, Kaneko T. Protective effect of epigallocatechin gallate and esculetin on oxidative DNA damage induced by psoralen plus ultraviolet-A therapy. Biosci Biotechnol Biochem 2005; 69: 620-622
    CrossrefPubMedSuche in Google Scholar
  • 16 Pittler MH, Ernst E. Horse chestnut seed extract for chronic venous insufficiency. Cochrane Database Syst Rev 2002; CD003230
    PubMedSuche in Google Scholar
  • 17 Ghafourian T, Zandasrar P, Hamishekar H, Nokhodchi A. The effect of penetration enhancers on drug delivery through skin: a QSAR study. J Control Release 2004; 99: 113-125
    CrossrefPubMedSuche in Google Scholar
  • 18 Moghimi HR, Williams AC, Barry BW. Enhancement by terpenes of 5-fluorouracil permeation through the stratum corneum: model solvent approach. J Pharm Pharmacol 1998; 50: 955-964
    CrossrefPubMedSuche in Google Scholar
  • 19 Ibrahim SA, Li SK. Efficiency of fatty acids as chemical penetration enhancers: mechanisms and structure enhancement relationship. Pharm Res 2010; 27: 115-125
    CrossrefPubMedSuche in Google Scholar
  • 20 Femenía-Font A, Balaguer-Fernández C, Merino V, Rodilla V, López-Castellano A. Effect of chemical enhancers on the in vitro percutaneous absorption of sumatriptan succinate. Eur J Pharm Biopharm 2005; 61: 50-55
    CrossrefPubMedSuche in Google Scholar
  • 21 Jenke DR. Chromatographic method validation: a review of current practices and procedures. I. General concepts and guidelines. J Liq Chrom Rel Technol 1996; 19: 719-736
    PubMedSuche in Google Scholar
  • 22 Jenke DR. Chromatographic method validation: a review of current practices and procedures. II. Guidelines for primary validation parameters. J Liq Chrom Rel Technol 1996; 19: 737-757
    PubMedSuche in Google Scholar
  • 23 OECD. Test No. 428: Skin absorption: In vitro method. OECD guidelines for the testing of chemicals, Section 4. Paris: OECD Publishing; 2004
    Suche in Google Scholar
  • 24 López A, Llinares F, Cortell C, Herráez M. Comparative enhancer effects of Span20 with Tween20 and Azone on the in vitro percutaneous penetration of compounds with different lipophilicities. Int J Pharm 2000; 202: 133-140
    CrossrefPubMedSuche in Google Scholar
  • 25 Borrás-Blasco J, Díez-Sales O, López A, Herráez-Domínguez M. A mathematical approach to predicting the percutaneous absorption enhancing effect of sodium lauryl sulphate. Int J Pharm 2004; 269: 121-129
    CrossrefPubMedSuche in Google Scholar
  • 26 Scheuplein RJ. Mechanism of percutaneous absorption. II. Transient diffusion and the relative importance of various routes of skin penetration. J Invest Dermatol 1967; 48: 79-88
    PubMedSuche in Google Scholar
  • 27 Lacy A, OʼKennedy R. Studies on coumarins and coumarin-related compounds to determine their therapeutic role in the treatment of cancer. Curr Pharm Des 2004; 10: 3797-3811
    CrossrefPubMedSuche in Google Scholar
  • 28 Zhou L, Kang J, Fan L, Ma XC, Zhao HY, Han J, Wang BR, Guo DA. Simultaneous analysis of coumarins and secoiridoids in Cortex Fraxini by high-performance liquid chromatography-diode array detection-electrospray ionization tandem mass spectrometry. J Pharm Biomed Anal 2008; 47: 39-46
    CrossrefPubMedSuche in Google Scholar
  • 29 Tsai TH, Huang CT, Shum AY, Chen CF. Simultaneous blood and biliary sampling of esculetin by microdialysis in the rat. Life Sci 1999; 65: 1647-1655
    CrossrefPubMedSuche in Google Scholar
  • 30 Shi Z, Zhu X, Zhang H. Micelle-mediated extraction and cloud point preconcentration for the analysis of aesculin and aesculetin in Cortex fraxini by HPLC. J Pharm Biomed Anal 2007; 44: 867-873
    CrossrefPubMedSuche in Google Scholar
  • 31 Tetko IV, Gasteiger J, Todeschini R, Mauri A, Livingstone D, Ertl P, Palyulin VA, Radchenko EV, Zefirov NS, Makarenko AS, Tanchuk VY, Prokopenko VV. Virtual computational chemistry laboratory – design and description. J Comput Aid Mol Des 2005; 19: 453-463
    CrossrefPubMedSuche in Google Scholar
  • 32 del Rio-Sancho S, Serna-Jimenez CE, Calatayud-Pascual A, Balaguer-Fernandez C, Femenia-Font A, Merino V, Lopez-Castellano A. Transdermal absorption of memantine. Effect of chemical enhancers, iontophoresis and role of enhancer lipophilicity. Eur J Pharm Biopharm 2012; 82: 164-170
    CrossrefPubMedSuche in Google Scholar
  • 33 Lewis D, Hadgraft J. Mixed monolayers of dipalmitolphospatidyl-choline with Azone or oleic acid at the air-water interface. Int J Pharm Sci 1990; 75: 176-181
    PubMedSuche in Google Scholar
  • 34 Díez-Sales O, Watkinson AC, Herráez-Domínguez M, Javaloyes C, Hadgraft J. A mechanistic investigation of the in vitro human permeation enhancing effect of Azone®. Int J Pharm 1996; 129: 33-40
    CrossrefPubMedSuche in Google Scholar
  • 35 Williams AC, Barry BW. Terpenes and the lipid-protein-partitioning theory of skin penetration enhancement. Pharm Res 1991; 8: 17-24
    CrossrefPubMedSuche in Google Scholar