COMPARISONS OF THE HISTOLOGICAL MORPHOLOGY AND IN VITRO PERCUTANEOUS ABSORPTION OF CAFFEINE IN SHED SNAKE SKIN AND HUMAN SKIN
DOI:
https://doi.org/10.26873/SVR-839-2020Abstract
The employment of excised skin (human or animal) mounted in diffusion cells is frequently used for the characterization of biopharmaceutical properties of topical semisolids dosage forms. Reptile skin from snake appears to be a useful alternative to other animal and human skins in assessing the potential for transdermal drug delivery. The aim of the study was to compare human and snake skin from a histological point of view. Furthermore the absorption of caffeine, as a hydrophilic model substance, was compared on snake shed skins (two anatomical locations; ventral and dorsal), from three different species, Python regius, Epicrates maurus colombianus, Lampropeltis triangulum campbelli, and human skin. Snake skin shows histological similarity to human Stratum corneum in term of thickness and composition. Regarding the absorption, the cumulative amount of caffeine increased linearly with time through the dorsal and ventral shed skins of all 3 species. Except for Lampropeltis triangulum campbelli ventral skin, the caffeine permeation behavior obtained on all snake shed skins evaluated was in a similar range as on human skin. One main advantage of shed skin, is that snakes molt regularly and can provide many sheds, that can be obtained without sacrificing the animals.
Key words: caffeine; transdermal; shed skin; in vitro; snake; topical formulation
PRIMERJAVA HISTOLOŠKE ZGRADBE TER PERKUTANE ABSORPCIJE KOFEINA IN VITRO V LEVKU KAČ IN ČLOVEŠKI KOŽI
Povzetek: Koža (človeškega ali živalskega izvora) se pogosto uporablja kot orodje za proučevanje biofarmacevtskih lastnosti topikalnih zdravil. Koža kač bi lahko bila uporabna alternativa drugim živalskim kožam in človeški koži pri oceni sposobnosti prenosa zdravil preko kože. Cilj študije je bil histološka primerjava človeške in kačje kože ter primerjava absorpcije kofeina kot hidrofilne modelne snovi na levkih kač iz dorzalnega in ventralnega področja treh različnih vrst kač: kraljevega pitona (Python regius), mavričnega udava (Epicrates maurus colombianus), mlečne kače (Lampropeltis triangulum campbelli). Kačja koža je histološko podobna človeški glede debeline in sestave roženi plasti (stratum corneum). Glavna prednost levitve kač je, da se dogaja večkrat, kar omogoča pridobitev več levkov, ki se jih lahko pridobi brez žrtvovanja živali. Rezultati so pokazali, da se je skupna količina kofeina sčasoma linearno povečevala v dorzalnih in ventralnih levkih pri vseh treh vrstah kač, razen na na ventralnem področju levka mlečne kače (Lampropeltis triangulum campbelli), pri katerem je bila prehodnost kofeina podobna kot pri prehodu skozi človeško kožo.
Ključne besede: kofein; transdermalno; levek; in vitro; kača; topikalni pripravek
References
(1.) TsangVL, Bhatia SN. Three dimensional tissue fabrication. Adv Drug Deliv Rev 2004; 56(11): 1635–47. doi:10.1016/j.addr.2004.05.001
(2.) Kim JB. Three-dimensional in vitro tissue culture models of breast cancer-a review. Breast Cancer Res Treat 2004; 85(3): 281–91. doi:10.1023/B:BREA.0000025418.88785.2b
(3.) Kolar R. Animal experimentation. Sci Eng Ethics 2006; 12(1): 111–22. doi:10.1007/s11948-006-0011-1
(4.) EMA Guideline on the principles of regulatory acceptance of 3Rs (replacement, reduction, refinement) testing approaches. EMA/CHMP/CVMP/JEG-3Rs/450091/2012. London : Euoropean Medicines Agency, 2016. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-principles-regulatory-acceptance-3rs-replacement-reduction-refinement-testing-approaches_en (25. Sept. 2019)
(5.) OECD. Test no. 428: Skin absorption: In vitro method. In: Guidelines for the testing of chemicals, Section 4: Health effects. Paris : OECD Publishing, 2004. doi:10.1787/9789264071087-en (9. July 2018)
(6.) Ngawhirunpat T, Panomsuk S, Opanasopit P, Rojanarata T, Hatanaka T. Comparison of the percutaneous absorption of hydrophilic and lipophilic compounds in shed snake skin and human skin. Pharmazie 2006: 61(4): 331–5.
(7.) Higuchi T, Kans L. Method for in vitro determination of transdermal absorption: [patent number US4771004, Sept 13, 1988].
(8.) Haigh JM, Beyssac E, Chanet L, Aiache JM. In vitro permeation of progesterone from a gel through the shed skin of three different snake species. Int J Pharm 1998; 170(2): 151–6. doi:10.1016/S0378-5173(98)00064-7
(9.) Herman A, Herman AP. Caffeine‘s mechanisms of action and its cosmetic use. Skin Pharmacol Physiol 2013; 26: 8–14. doi:10.1159/000343174
(10.) Caffeine. In: DrugBank. Ottawa : Canadian Institutes of Health Research. https://www.drugbank.ca/drugs/DB00201 (10. Jan. 2020)
(11.) Balamurugan M, Weli MA, Edwards G, Al-Harrsi A, Al-Kharusi Z. In vitro permeation studies of commercially available diclofenac sodium gel (sample analysis using LC-MS/MS) through the two different shed snake skins obtained from various regions of sultanate of Oman: a pilot study. Latin Am J Pharm 2013; 32 (7): 1069–73.
(12.) Rigg PC, Barry BW. Shed snake skin and hairless mouse skin as a model membrane for human skin during permeation studies. J Invest Dermatol Baltimore 1990: 94(2): 235–40. doi:10.1111/1523-1747.ep12874561
(13.) Mader DR. Reptile medicine and surgery. 2nd ed.. St. Louis : Saunders, 2006: 1242 p.
(14.) Roberts JB. Use of squamate epidermis in percutaneous absorption studies: a review. J Toxicol Cutaneous Ocul Toxicol 1986; 5(4): 319–24. doi:10.3109/15569528609036305
(15.) Chang C, Wu P, Baker U, Maini PK, Alibardi L, Cheng-Ming C. Reptile scale paradigm: Evo-Devo pattern formation and regeneration. Int J Dev Biol 2009: 53: 813–26. doi:10.1387/ijdb.072556cc
(16.) Hatanaka T, Inuma M, Sugibayashi K, Morimoto Y. Prediction of skin permeability of drugs I: Comparison with artificial membrane. Chem Pharm Bull 1990; 38: 3452–9. htpp://doi.org/10.1248/cpb.38.3452
(17.) Schäfer-Korting M, Bock U, Gamer A, et al. Reconstructed human epidermis for skin absorption testing: results of the German prevalidation study. ATLA 2006; 34: 283–94. doi:10.1177/026119290603400312
(18.) Torri C, Mangoni A, Teta R, et al. Skin lipid structure controls water permeability in snake molts. J Struct Biol 2014; 185: 99–106. doi:org/10.1016/j.jsb.2013.10.007
(19.) Klein MCG, Gorb SN. Epidermis architecture and material properties of the skin of four snake species. J R Soc Interface 2012; 9: 3140–55. doi:10.1098/rsif.2012.0479