Abstract
The permeability enhancement effect of oleic acid (OA) and propylene glycol (PG) as well as their (1:1 v/v) combined mixture was studied using rat skin. The percutaneous drug administration is a challenge and an opportunity for drug delivery. To date, there is limited research that illustrates the mechanism of penetration enhancers and their combinations on the skin. This project aims to explore the skin diffusion and penetration enhancement of PG, OA, and a combination of PG-OA (1:1 v/v) on rat skin and to identify the potential synergistic effect of the two enhancers utilizing Raman spectroscopy. Dissected dorsal skin was treated with either PG or OA or their combination for predetermined time intervals after which the Raman spectra of the treated skin were collected with the enhancer. A spectrum of the wiped and the washed skin were also collected. The skin integrity was tested before and after exposure to PG. The skin histology proved that the skin integrity has been maintained during experiments and the results indicated that OA disrupted rat skin lipid as evident by changes in the lipid peak. The results also showed that PG and OA improved the diffusion of each other and created faster, yet reversible changes of the skin peaks. In conclusion, Raman spectroscopy is a potential tool for ex vivo skin diffusion studies. We also concluded that PG and OA have potential synergistic reversible effect on the skin.
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Subramanyan K, Misra M, Mukherjee S, Ananthapadmanabhan KP. Advances in the materials science of skin: a composite structure with multiple functions. MRS Bull. 2007;32(10):770–8.
Marren K. Dimethyl sulfoxide: an effective penetration enhancer for topical administration of NSAIDs. Phys Sportsmed. 2011;39(3):75–82.
Simon LS, Grierson LM, Naseer Z, Bookman AAM, Shainhouse ZJ. Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of topical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis: pain, 2009;143(3):238–245.
Tfayli A, Piot O, Pitre F, Manfait M. Follow-up of drug permeation through excised human skin with confocal Raman microspectroscopy. Eur Biophys J. 2007;36(8):1049–58.
Lai-Cheong JE, McGrath JA. Structure and function of skin, hair and nails. Medicine (Baltimore). 2009;37(5):223–6.
Mao G, Flach CR, Mendelsohn R, Walters RM. Imaging the distribution of sodium dodecyl sulfate in skin by confocal Raman and infrared microspectroscopy. Pharm Res. 2012;29(8):2189–201.
Kaushik D, Batheja P, Kilfoyle B, Rai V, Michniak-Kohn B. Percutaneous permeation modifiers: enhancement versus retardation. Expert Opin Drug Deliv. 2008;5(5):517–29.
Mélot M, Pudney PDA, Williamson A-M, Caspers PJ, Van Der Pol A, Puppels GJ. Studying the effectiveness of penetration enhancers to deliver retinol through the stratum cornum by in vivo confocal Raman spectroscopy. J Control Release. 2009;138(1):32–9.
Williams AC, Barry BW. Penetration enhancers. Adv Drug Deliv Rev. 2004;56(5):603–18.
Lane ME. Skin penetration enhancers. Int J Pharm. 2013;447(1–2):12–21.
da Silva ER, Faria de Freitas ZM, Brito Gitirana L de, Ricci-Júnior E.Improving the topical delivery of zinc phthalocyanine using oleic acid as a penetration enhancer: in vitro permeation and retention. Drug Dev Ind Pharm 2011;37(5):569–575.
Tfayli A, Piot O, Draux F, Pitre F, Manfait M. Molecular characterization of reconstructed skin model by Raman microspectroscopy: comparison with excised human skin. Biopolymers. 2007;87(4):261–74.
Barker AS, Loudon R. Response functions in the theory of Raman scattering by vibrational and polariton modes in dielectric crystals. Rev Mod Phys. 1972;44(1):18–47.
Essendoubi M, Gobinet C, Reynaud R, Angiboust JF, Manfait M, Piot O. Human skin penetration of hyaluronic acid of different molecular weights as probed by Raman spectroscopy. Skin Res Technol. 2016;22(1):55–62.
van Logtestijn MDA, Domínguez-Hüttinger E, Stamatas GN, Tanaka RJ. Resistance to water diffusion in the stratum corneum is depth-dependent. Brandner JM, editor. PLOS ONE. 2015, 10(2):e0117292.
Jermyn M, Desroches J, Aubertin K, St-Arnaud K, Madore W-J, De Montigny E, et al. A review of Raman spectroscopy advances with an emphasis on clinical translation challenges in oncology. Phys Med Biol. 2016;61(23):R370–400.
Anigbogu ANC, Williams AC, Barry BW, Edwards HGM. Fourier transform raman spectroscopy of interactions between the penetration enhancer dimethyl sulfoxide and human stratum corneum. Int J Pharm. 1995;125(2):265–82.
Hoelgaard A, Møllgaard B. Dermal drug delivery—improvement by choice of vehicle or drug derivative. J Control Release. 1985;2:111–20.
Notman R, Noro M, O’Malley B, Anwar J. Molecular basis for dimethylsulfoxide (DMSO) action on lipid membranes. J Am Chem Soc. 2006;128(43):13982–3.
Brinkmann I, Müller-Goymann CC. An attempt to clarify the influence of glycerol, propylene glycol, isopropyl myristate and a combination of propylene glycol and isopropyl myristate on human stratum corneum. Pharm. 2005;60(3):215–20.
Saar BG, Contreras-Rojas LR, Xie XS, Guy RH. Imaging drug delivery to skin with stimulated Raman scattering microscopy. Mol Pharm. 2011;8(3):969–75.
Mujica Ascencio S, Choe C, Meinke MC, Müller RH, Maksimov GV, Wigger-Alberti W, et al. Confocal Raman microscopy and multivariate statistical analysis for determination of different penetration abilities of caffeine and propylene glycol applied simultaneously in a mixture on porcine skin ex vivo. Eur J Pharm Biopharm. 2016;104:51–8.
Naik A, Pechtold LARM, Potts RO, Guy RH. Mechanism of oleic acid-induced skin penetration enhancement in vivo in humans. J Control Release. 1995;37(3):299–306.
Larrucea E, Arellano A, Santoyo S, Ygartua P. Combined effect of oleic acid and propylene glycol on the percutaneous penetration of tenoxicam and its retention in the skin. Eur J Pharm Biopharm Off J Arbeitsgemeinschaft Für Pharm Verfahrenstechnik EV. 2001;52(2):113–9.
Pidgeon C, editor. Advanced tutorials for the biomedical sciences: animations, simulations, and calculations using Mathematica. New York: VCH Publishers; 1996. 275 p.
Bruin C. Logarithmic terms in the diffusion coefficient for the Lorentz gas. Phys Rev Lett. 1972;29(25):1670–4.
Verberne AJ, Sartor DM, Berke A. Midline medullary depressor responses are mediated by inhibition of RVLM sympathoexcitatory neurons in rats. Am J Phys. 1999;276(4 Pt 2):R1054–62.
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The authors would like to thank SACM and MCPHS University Boston for the financial support of the study.
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Atef, E., Altuwaijri, N. Using Raman Spectroscopy in Studying the Effect of Propylene Glycol, Oleic Acid, and Their Combination on the Rat Skin. AAPS PharmSciTech 19, 114–122 (2018). https://doi.org/10.1208/s12249-017-0800-7
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DOI: https://doi.org/10.1208/s12249-017-0800-7