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Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement pp 251–271Cite as

Nonionic Surfactants: Polyethylene Glycol (PEG) Ethers and Fatty Acid Esters as Penetration Enhancers

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Abstract

Polyethylene glycols (PEGs) are a wide family of synthetic polyethers available in a range of molecular weights. Due to their multifunctional properties, PEGs are used both as such and/or in the form of nonionic derivatives in the formulation of cosmetics and medical products. In consideration of their physicochemical characteristics, they can penetrate into the intercellular regions of the stratum corneum, increase the fluidity and solubilise lipid components as well as bind to keratin filaments causing a disruption within corneocytes.

In the current chapter, the performances of PEG ethers and esters as penetration enhancer are discussed according to the referenced literature underlining the influences of the physicochemical properties of surfactants (i.e. functional groups, size of the polar head groups, polyoxyethylene chain length, alkyl chain length, degree and position of unsaturation and the hydrophile–lipophile balance) on the penetration of chemicals incorporated in various types of formulations, such as parenteral, topical, ophthalmic, oral and rectal formulations.

Keywords

  • Nonionic surfactant
  • Polyethylene glycol ether
  • Polyethylene glycol fatty acid ester
  • Polyethylene glycol derivative
  • Penetration enhancer
  • Percutaneous absorption

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References

  • Asmussen C (2013) Chemische charakterisierung von alkylethoxylaten. http://ublibsprod.ub.tu-berlin.de/F/LIVRV5X9HJUPN4SLC6VE4NRGTTQXSUJD29VV2D7J8VG2Q2457M-18153?func=full-set-set&set_number=002801&set_entry=000001&format=999. Accessed 9 Jan 2013

  • Attwood D, Florence AT (1983) Surfactant systems: their chemistry, pharmacy and biology. Chapman and Hall Ltd, London

    CrossRef  Google Scholar 

  • Aungst B (1995) Fatty acids as skin permeation enhancers. In: Smith EW, Maibach HI (eds) Percutaneous penetration enhancers. CRC Press, Boca Raton, pp 277–287

    Google Scholar 

  • Aungst BJ, Rogers NJ, Shefter E (1986) Enhancement of naloxone penetration through human skin in vitro using fatty acids, fatty alcohols, surfactants, sulfoxides and amides. Int J Pharm 33:225–234

    CAS  CrossRef  Google Scholar 

  • Bailey FE, Koleske JV (1976) Poly(ethylene oxide). Academic Press Inc, New York

    Google Scholar 

  • Bárány E, Lindberg M, Lodén M (2000) Unexpected skin barrier influence from nonionic emulsifiers. Int J Pharm 195:189–195

    CrossRef  PubMed  Google Scholar 

  • Breuer MM (1979) The interaction between surfactants and keratinous tissues. J Soc Cosmet Chem 30:41–64

    CAS  Google Scholar 

  • Casiraghi A, Grigoli M, Cilurzo F, Gennari CGM, Rossoni G, Minghetti P (2012) The influence of the polar head and the hydrophobic chain on the skin penetration enhancement effect of poly(ethylene glycol) derivatives. AAPS PharmSciTech 13:247–253

    PubMed Central  CAS  CrossRef  PubMed  Google Scholar 

  • Cázares-Delgadillo J, Naik A, Kalia YN, Quintanar-Guerrero D, Ganem-Quintanar A (2005) Skin permeation enhancement by sucrose esters: a pH dependent phenomenon. Int J Pharm 297:204–212

    CrossRef  PubMed  Google Scholar 

  • Cooper ER (1984) Increased skin permeability for lipophilic molecules. J Pharm Sci 73:1153–1156

    CAS  CrossRef  PubMed  Google Scholar 

  • Dalvi UG, Zatz JL (1981) Effects of nonionic surfactants on penetration of dissolved benzocaine through hairless mouse skin. J Soc Cosmet Chem 32:87–94

    CAS  Google Scholar 

  • Endo M, Yamamoto T, Ijuin T (1996) Effect of non ionic surfactants on the percutaneous absorption of tenoxicam. Chem Pharm Bull 44:865–867

    CAS  CrossRef  PubMed  Google Scholar 

  • Florence AT (1981) Surfactant interactions with biomembranes and drug absorption. Pure Appl Chem 53:2057–2068

    CAS  CrossRef  Google Scholar 

  • Florence AT, Tucker IG, Walters KA (1984) Interactions of non-ionic alkyl and aryl ethers with membranes and other biological systems. In: Rosen MJ (ed) Structure: performance relationships in surfactants, ACS symposium series., pp 189–207

    CrossRef  Google Scholar 

  • French EJ, Pouton CW, Walters KA (1993) Mechanism and prediction of non-ionic surfactant effects on skin permeability. In: Walters KA, Hadgraft J (eds) Pharmaceutical skin penetration enhancement. Marcel Dekker, New York, pp 113–143

    Google Scholar 

  • Fruijtier-Pölloth C (2005) Safety assessment on polyethylene glycols (PEGs) and their derivatives as used in cosmetic products. Toxicology 214:1–38

    CrossRef  PubMed  Google Scholar 

  • Furuishi T, Oda S, Saito H, Fukami T, Suzuki T, Tomono K (2007) Effect of permeation enhancers on the in vitro percutaneous absorption of pentazocine. Biol Pharm Bull 30(7):1350–1353

    CAS  CrossRef  PubMed  Google Scholar 

  • Hadgraft J, Walters KA (1994) Skin penetration enhancement. J Derm Treat 5:43–47

    CrossRef  Google Scholar 

  • Kanikkannan N, Kandimalla K, Lamba SS, Singh M (2000) Structure-activity relationship of chemical penetration enhancers in transdermal drug delivery. Curr Med Chem 7:593–608

    CAS  CrossRef  PubMed  Google Scholar 

  • Kim HS, Oh SY (2011) Effect of polyoxyethylene alkyl esters on permeation enhancement and impedance of skin. Biomol Ther 19:109–117

    CAS  CrossRef  Google Scholar 

  • Kim JH, Lee CH, Choi HK (2002) Transdermal delivery of physostigmine: effects of enhancers and pressure-sensitive adhesives. Drug Dev Ind Pharm 28:833–839

    CAS  CrossRef  PubMed  Google Scholar 

  • López A, Llinares F, Cortell C, Herráez M (2000) Comparative enhancer effects of Span®20 with Tween®20 and Azone® on the in vitro percutaneous penetration of compounds with different lipophilicities. Int J Pharm 202:133–140

    CrossRef  PubMed  Google Scholar 

  • Morimoto K, Tojima H, Haruta T, Suzuki M, Kakemi M (1996) Enhancing effects of unsaturated fatty acids with various structures on the permeation of indomethacin through rat skin. J Pharm Pharmacol 48:1133–1137

    CAS  CrossRef  PubMed  Google Scholar 

  • Myoung Y, Choi HK (2002) Effects of vehicles and pressure sensitive adhesives on the penetration of isosorbide dinitrate across the hairless mouse skin. Drug Deliv 9:121–126

    CrossRef  PubMed  Google Scholar 

  • Nishiyama T, Iwata Y, Nakajima K, Mitsui T (1983) In vivo percutaneous absorption of polyoxyethylene lauryl ether surfactants in hairless mice. J Soc Cosmet Chem 34:263–271

    CAS  Google Scholar 

  • Okuyama H, Ikeda Y, Kasai S, Imamori K, Takayama K, Nagai T (1999) Influence of non-ionic surfactants, pH and propylene glycol on percutaneous absorption of piroxicam from cataplasm. Int J Pharm 186:141–148

    CAS  CrossRef  PubMed  Google Scholar 

  • Park ES, Chang SY, Hahn M, Chi SC (2000) Enhancing effect of polyoxyethylene alkyl ethers on the skin permeation of ibuprofen. Int J Pharm 209:109–119

    CAS  CrossRef  PubMed  Google Scholar 

  • Schaefer H, Redelmeier TE (1996) Strategies to alter skin barrier properties. In: Schaefer H, Redelmeier TE (eds) Skin barrier: principles of percutaneous absorption. Karger, Basel, p 169

    Google Scholar 

  • Schott H (1973) Effect of chain length in homologous series of anionic surfactants on irritant action and toxicity. J Pharm Sci 62:341–343

    CAS  CrossRef  PubMed  Google Scholar 

  • Shin SC, Cho CW, Oh IJ (2001) Effects of non-ionic surfactants as permeation enhancers towards piroxicam from the poloxamer gel through rat skins. Int J Pharm 222:199–203

    CAS  CrossRef  PubMed  Google Scholar 

  • Songkro S (2009) An overview of skin penetration enhancers: penetration enhancing activity, skin irritation potential and mechanism of action. Songklanakarin J Sci Technol 31:299–321

    Google Scholar 

  • Vavrova K, Zbytovska J, Hrabalek A (2005) Amphiphilic transdermal permeation enhancers: structure-activity relationships. Curr Med Chem 12:2273–2291

    CAS  CrossRef  PubMed  Google Scholar 

  • Walters KA (1989) Penetration enhancers and their use in transdermal therapeutic systems. In: Hadgraft J, Guy RH (eds) Transdermal drug delivery. Marcel Dekker, New York, pp 197–246

    Google Scholar 

  • Walters KA, Dugard PH, Florence AT (1981) Non-ionic surfactants and gastric mucosal transport of paraquat. J Pharm Pharmacol 33:207–213

    CAS  CrossRef  PubMed  Google Scholar 

  • Walters KA, Florence AT, Dugard PH (1982) Non-ionic surfactants and the membrane transport of barbiturates in goldfish. Int J Pharm 10:153–163

    Google Scholar 

  • Walters KA, Florence AT, Dugard PH (1983) Interaction of polyoxyethylene alkyl ethers with cholesterol monolayers. J Colloid Interface Sci 89:584–587

    CrossRef  Google Scholar 

  • Walters KA, Walker M, Olejnik O (1988) Non-ionic surfactant effects on hairless mouse skin permeability characteristics. J Pharm Pharmacol 40:525–529

    CAS  CrossRef  PubMed  Google Scholar 

  • Walters KA, Bialik W, Brain KR (1993) The effects of surfactants on penetration across the skin. Int J Cosmet Sci 15:260–271

    CAS  CrossRef  PubMed  Google Scholar 

  • Zaslavsky BY, Ossipov NN, Krivitch VS, Baholdina LP, Rogozhin SV (1978) Action of surface-active-substances on biological membranes. II. Haemolytic activity of non-ionic surfactants. Biochim Biophys Acta 507:1–7

    CAS  CrossRef  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutical Science, Università degli Studi di Milano, Via Giuseppe Colombo 71, Milan, 20133, Italy

    Antonella Casiraghi, Francesca Selmin, Paola Minghetti, Francesco Cilurzo & Luisa Montanari

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  1. Antonella Casiraghi
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  2. Francesca Selmin
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  3. Paola Minghetti
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  4. Francesco Cilurzo
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  5. Luisa Montanari
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Correspondence to Antonella Casiraghi .

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Editors and Affiliations

  1. Department of Manufacturing, Apoteka "Beograd", Belgrade, Serbia

    Nina Dragicevic

  2. Dermatology Clinic, University of California San Francisco Dermatology Clinic, San Francisco, USA

    Howard I. Maibach

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Casiraghi, A., Selmin, F., Minghetti, P., Cilurzo, F., Montanari, L. (2015). Nonionic Surfactants: Polyethylene Glycol (PEG) Ethers and Fatty Acid Esters as Penetration Enhancers. In: Dragicevic, N., Maibach, H. (eds) Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-47039-8_15

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  • DOI: https://doi.org/10.1007/978-3-662-47039-8_15

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