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Nanoemulsions in Dermal Drug Delivery

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Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement

Abstract

This chapter provides an overview of nanoemulsions, elucidating their properties and their use in dermal drug delivery. The adaptation of these submicron-sized emulsion systems for different tasks of topical application is presented, and promising prospects as well as limitations are discussed. Nanoemulsions are generally aimed at targeting the outermost skin layers. Thus, recent findings of interest are presented, highlighting how modification of formulation parameters such as droplet size and surface charge or addition of specific surfactants, oil types and penetration enhancers can affect drug delivery. In addition to the high skin friendliness and physical stability of nanoemulsions, enhanced in vivo efficacy of drugs has been reported due to the specific morphology and composition of these systems. Since both lipophilic and hydrophilic actives can be incorporated, nanoemulsions represent vehicles of particular interest for dermal and cosmetic applications. Future research dealing with the biological effects of such systems in vivo is being anticipated with great interest.

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References

  • Alves PM, Pohlmann AR, Guterres SS (2005) Semisolid topical formulations containing nimesulide-loaded nanocapsules, nanospheres or nanoemulsion: development and rheological characterization. Pharmazie 60(12):900–904

    CAS  PubMed  Google Scholar 

  • Anton N, Vandamme TF (2011) Nano-emulsions and micro-emulsions: clarifications of the critical differences. Pharm Res 28:978–985

    Article  CAS  PubMed  Google Scholar 

  • Anton N, Gayet P, Benoit JP, Saulnier P (2007) Nano-emulsions and nanocapsules by the PIT method: an investigation on the role of the temperature cycling on the emulsion phase inversion. Int J Pharm 344(1–2):44–52

    Article  CAS  PubMed  Google Scholar 

  • Anton N, Mojzisova H, Porcher E, Benoit JP, Saulnier P (2010) Reverse micelle-loaded lipid nano-emulsions: new technology for nano-encapsulation of hydrophilic materials. Int J Pharm 398(1–2):204–209

    Article  CAS  PubMed  Google Scholar 

  • Baker MT, Naguib M (2005) Propofol: the challenges of formulation. Anesthesiology 103(4):860–876

    Article  CAS  PubMed  Google Scholar 

  • Baspinar Y, Borchert HH (2012) Penetration and release studies of positively and negatively charged nanoemulsions–is there a benefit of the positive charge? Int J Pharm 430(1–2):247–252

    Article  CAS  PubMed  Google Scholar 

  • Benita S (1999) Prevention of topical and ocular oxidative stress by positively charged submicron emulsion. Biomed Pharmacother 53(4):193–206

    Article  CAS  PubMed  Google Scholar 

  • Benita S, Levy MY (1993) Submicron emulsions as colloidal drug carriers for intravenous administration: comprehensive physicochemical characterization. J Pharm Sci 82(11):1069–1079

    Article  CAS  PubMed  Google Scholar 

  • Calder PC, Jensen GL, Koletzko BV, Singer P, Wanten GJ (2010) Lipid emulsions in parenteral nutrition of intensive care patients: current thinking and future directions. Intensive Care Med 36(5):735–749

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Calderilla-Fajardo SB, Cazares-Delgadillo J, Villalobos-Garcia R, Quintanar-Guerrero D, Ganem-Quintanar A, Robles R (2006) Influence of sucrose esters on the in vivo percutaneous penetration of octyl methoxycinnamate formulated in nanocapsules, nanoemulsion, and emulsion. Drug Dev Ind Pharm 32(1):107–113

    Article  CAS  PubMed  Google Scholar 

  • Cazares-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(1–2):204–212

    Article  CAS  PubMed  Google Scholar 

  • Cevc G, Vierl U (2010) Nanotechnology and the Transdermal route: a state of the art review and critical appraisal. J Control Release 141(3):277–299

    Article  CAS  PubMed  Google Scholar 

  • Chiesa M, Garg J, Kang YT, Chen G (2008) Thermal conductivity and viscosity of water-in-oil nanoemulsions. Colloids Surf A Physicochem Eng Asp 326:67–72

    Article  CAS  Google Scholar 

  • Chung H, Kim TW, Kwon M, Kwon IC, Jeong SY (2001) Oil components modulate physical characteristics and function of the natural oil emulsions as drug or gene delivery system. J Control Release 71(3):339–350

    Article  CAS  PubMed  Google Scholar 

  • Cortés-Muñoz M, Chevalier-Lucia D, Dumay E (2009) Characteristics of submicron emulsions prepared by ultra-high pressure homogenisation: Effect of chilled or frozen storage. Food Hydrocoll 23(3):640–654

    Article  Google Scholar 

  • Dirschka T, Radny P, Dominicus R, Mensing H, Bruning H, Jenne L et al (2012) Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a multicentre, randomized, observer-blind phase III study in comparison with a registered methyl-5-aminolaevulinate cream and placebo. Br J Dermatol 166(1):137–146

    Article  CAS  PubMed  Google Scholar 

  • Eskandar NG, Simovic S, Prestidge CA (2009) Nanoparticle coated submicron emulsions: sustained in-vitro release and improved dermal delivery of all-trans-retinol. Pharm Res 26(7):1764–1775

    Google Scholar 

  • Fang JY, Leu YL, Chang CC, Lin CH, Tsai YH (2004) Lipid nano/submicron emulsions as vehicles for topical flurbiprofen delivery. Drug Deliv 11(2):97–105

    Article  CAS  PubMed  Google Scholar 

  • Fernandez P, André V, Rieger J, Kuehnle A (2004) Nano-emulsion formation by emulsion phase inversion. Colloids Surf A Physicochem Eng Asp 251:53–58

    Article  CAS  Google Scholar 

  • Fox CB (2009) Squalene emulsions for parenteral vaccine and drug delivery. Molecules 14(9):3286–3312

    Article  CAS  PubMed  Google Scholar 

  • Friedman DI, Schwarz JS, Weisspapir M (1995) Submicron emulsion vehicle for enhanced transdermal delivery of steroidal and nonsteroidal antiinflammatory drugs. J Pharm Sci 84(3):324–329

    Article  CAS  PubMed  Google Scholar 

  • Hoeller S, Sperger A, Valenta C (2009) Lecithin based nanoemulsions: a comparative study of the influence of non-ionic surfactants and the cationic phytosphingosine on physicochemical behaviour and skin permeation. Int J Pharm 370(1–2):181–186

    Article  CAS  PubMed  Google Scholar 

  • Hung CF, Fang CL, Liao MH, Fang JY (2007) The effect of oil components on the physicochemical properties and drug delivery of emulsions: tocol emulsion versus lipid emulsion. Int J Pharm 335(1–2):193–202

    Article  CAS  PubMed  Google Scholar 

  • Ibrahim SS, Awad GA, Geneidi A, Mortada ND (2009) Comparative effects of different cosurfactants on sterile prednisolone acetate ocular submicron emulsions stability and release. Colloids Surf B: Biointerfaces 69(2):225–231

    Article  CAS  PubMed  Google Scholar 

  • Jumaa M, Mueller BW (1998) The effect of oil components and homogenization conditions on the physicochemical properties and stability of parenteral fat emulsions. Int J Pharm 163:81–89

    Article  CAS  Google Scholar 

  • Kirjavainen M, Monkkonen J, Saukkosaari M, Valjakka-Koskela R, Kiesvaara J, Urtti A (1999) Phospholipids affect stratum corneum lipid bilayer fluidity and drug partitioning into the bilayers. J Control Release 58(2):207–214

    Article  CAS  PubMed  Google Scholar 

  • Klang V, Valenta C (2011) Lecithin-based nanoemulsions. J Drug Del Sci Tech 21(1):55–76

    Article  CAS  Google Scholar 

  • Klang SH, Parnas M, Benita S (1998) Emulsions as drug carriers – possibilities, limitations and future perspectives. In: Mueller RH, Benita S, Böhm BHL (eds) Emulsions and nanosuspensions for the formulation of poorly soluble drugs. Medpharm Scientific Publishers, Stuttgart, pp 31–56

    Google Scholar 

  • Klang V, Matsko N, Zimmermann AM, Vojnikovic E, Valenta C (2010) Enhancement of stability and skin permeation by sucrose stearate and cyclodextrins in progesterone nanoemulsions. Int J Pharm 393(1–2):152–160

    CAS  PubMed  Google Scholar 

  • Klang V, Matsko N, Raupach K, El-Hagin N, Valenta C (2011a) Development of sucrose stearate-based nanoemulsions and optimisation through gamma-cyclodextrin. Eur J Pharm Biopharm 79:58–67

    Article  CAS  PubMed  Google Scholar 

  • Klang V, Schwarz JC, Matsko N, Rezvani E, El-Hagin N, Wirth M et al (2011b) Semi-solid sucrose stearate-based emulsions as dermal drug delivery systems. Pharmaceutics 3:275–306

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Klang V, Matsko NB, Valenta C, Hofer F (2012a) Electron microscopy of nanoemulsions: an essential tool for characterisation and stability assessment. Micron 43:85–103

    Article  CAS  PubMed  Google Scholar 

  • Klang V, Schwarz JC, Lenobel B, Nadj M, Auböck J, Wolzt M et al (2012b) In vitro vs in vivo tape stripping: validation of the porcine ear model and penetration assessment of novel sucrose stearate emulsions. Eur J Pharm Biopharm 80:604–614

    Article  CAS  PubMed  Google Scholar 

  • Kotyla T, Kuo F, Moolchandani V, Wilson T, Nicolosi R (2008) Increased bioavailability of a transdermal application of a nano-sized emulsion preparation. Int J Pharm 347(1–2):144–148

    Article  CAS  PubMed  Google Scholar 

  • Lademann J, Otberg N, Richter H, Weigmann HJ, Lindemann U, Schaefer H et al (2001) Investigation of follicular penetration of topically applied substances. Skin Pharmacol Appl Skin Physiol 14(1):17–22

    Article  PubMed  Google Scholar 

  • Maisch T, Santarelli F, Schreml S, Babilas P, Szeimies RM (2010) Fluorescence induction of protoporphyrin IX by a new 5-aminolevulinic acid nanoemulsion used for photodynamic therapy in a full-thickness ex vivo skin model. Exp Dermatol 19(8):e302–e305

    Article  PubMed  Google Scholar 

  • Marxer EE, Brussler J, Becker A, Schummelfeder J, Schubert R, Nimsky C et al (2011) Development and characterization of new nanoscaled ultrasound active lipid dispersions as contrast agents. Eur J Pharm Biopharm 77(3):430–437

    Article  CAS  PubMed  Google Scholar 

  • Mason TG, Wilking JN, Meleson K, Chang CB, Graves SM (2006) Nanoemulsions: formation, structure, and physical properties. J Phys Condens Matter 18:R635–R666

    Article  CAS  Google Scholar 

  • McClements DJ (2012) Nanoemulsions versus microemulsions: terminology, differences, and similarities. Soft Matter 8:1719–1729

    Article  CAS  Google Scholar 

  • Mitri K, Shegokar R, Gohla S, Anselmi C, Mueller RH (2011) Lipid nanocarriers for dermal delivery of lutein: preparation, characterization, stability and performance. Int J Pharm 414(1–2):267–275

    Article  CAS  PubMed  Google Scholar 

  • Mou D, Chen H, Du D, Mao C, Wan J, Xu H et al (2008) Hydrogel-thickened nanoemulsion system for topical delivery of lipophilic drugs. Int J Pharm 353(1-2):270–6

    Article  CAS  PubMed  Google Scholar 

  • Mueller RH (1996) Zetapotential und Partikelladung in der Laborpraxis. Band 37, Paperback APV ed. Stuttgart: Wissenschaftliche Verlagsgesellschaft mbH

    Google Scholar 

  • Nokhodchi A, Shokri J, Dashbolaghi A, Hassan-Zadeh D, Ghafourian T, Barzegar-Jalali M (2003) The enhancement effect of surfactants on the penetration of lorazepam through rat skin. Int J Pharm 250(2):359–369

    Article  CAS  PubMed  Google Scholar 

  • Norden TP, Siekmann B, Lundquist S, Malmsten M (2001) Physicochemical characterisation of a drug-containing phospholipid-stabilised o/w emulsion for intravenous administration. Eur J Pharm Sci 13(4):393–401

    Article  CAS  PubMed  Google Scholar 

  • Piemi MP, Korner D, Benita S, Marty J-P (1999) Positively and negatively charged submicron emulsions for enhanced topical delivery of antifungal drugs. J Control Release 58(2):177–187

    Article  CAS  PubMed  Google Scholar 

  • Porras M, Solans C, González C, Martinez A, Guinart A, Gutiérrez JM (2004) Studies of formation of W/O nano-emulsions. Colloids Surf A Physicochem Eng Asp 249(1–3):115–118

    Article  CAS  Google Scholar 

  • Puglia C, Rizza L, Drechsler M, Bonina F (2010) Nanoemulsions as vehicles for topical administration of glycyrrhetic acid: characterization and in vitro and in vivo evaluation. Drug Deliv 17(3):123–129

    Article  CAS  PubMed  Google Scholar 

  • Schulz MB, Daniels R (2000) Hydroxypropyl methylcellulose (HPMC) as emulsifier for submicron emulsions: influence of molecular weight and substitution type on the droplet size after high-pressure homogenization. Eur J Pharm Biopharm 49(3):231–236

    Article  CAS  PubMed  Google Scholar 

  • Schwarz JC, Klang V, Karall S, Mahrhauser D, Resch GP, Valenta C (2012) Optimisation of multiple W/O/W nanoemulsions for dermal delivery of aciclovir. Int J Pharm 435(1):69–75

    Article  CAS  PubMed  Google Scholar 

  • Sole I, Pey CM, Maestro A, Gonzalez C, Porras M, Solans C et al (2010) Nano-emulsions prepared by the phase inversion composition method: preparation variables and scale up. J Colloid Interface Sci 344(2):417–423

    Article  CAS  PubMed  Google Scholar 

  • Sonneville-Aubrun O, Simonnet JT, L’Alloret F (2004) Nanoemulsions: a new vehicle for skincare products. Adv Colloid Interface Sci 108–109:145–149

    Article  PubMed  Google Scholar 

  • Spagnul A, Bouvier-Capely C, Phan G, Landon G, Tessier C, Suhard D et al (2011) Ex vivo decrease in uranium diffusion through intact and excoriated pig ear skin by a calixarene nanoemulsion. Eur J Pharm Biopharm 79(2):258–267

    Article  CAS  PubMed  Google Scholar 

  • Tadros T, Izquierdo P, Esquena J, Solans C (2004) Formation and stability of nano-emulsions. Adv Colloid Interface Sci 108–109:303–318

    Article  PubMed  Google Scholar 

  • Ullrich S, Metz H, Maeder K (2008) Sucrose ester nanodispersions: microviscosity and viscoelastic properties. Eur J Pharm Biopharm 70(2):550–555

    Article  CAS  PubMed  Google Scholar 

  • van Nieuwenhuyzen W, Szuhaj BF (1998) Effects of lecithins and proteins on the stability of emulsions. Fett-Lipid 100(7):282–291

    Article  Google Scholar 

  • Wabel C (1998) Influence of lecithin on structure and stability of parenteral fat emulsions [Dissertation]. Friedrich-Alexander-Universität, Erlangen-Nürnberg

    Google Scholar 

  • Yang SC, Benita S (2000) Enhanced absorption and drug targeting by positively charged submicron emulsions. Drug Dev Res 50(3–4):476–486

    Article  CAS  Google Scholar 

  • Yu C, Meng J, Chen J, Tang X (2009) Preparation of ergoloid mesylate submicron emulsions for enhancing nasal absorption and reducing nasal ciliotoxicity. Int J Pharm 375(1–2):16–21

    Article  CAS  PubMed  Google Scholar 

  • Zhou H, Yue Y, Liu G, Li Y, Zhang J, Gong Q et al (2010) Preparation and characterization of a lecithin nanoemulsion as a topical delivery system. Nanoscale Res Lett 5:224–230

    Article  PubMed Central  CAS  Google Scholar 

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Acknowledgement

The authors would like to thank Dr. Tim Maisch and co-workers for providing Fig. 18.2.

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Authors and Affiliations

  1. Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstraße 14, Vienna, 1090, Austria

    Victoria Klang & Claudia Valenta

  2. Research Platform ‘Characterisation of Drug Delivery Systems on Skin and Investigation of Involved Mechanisms’, University of Vienna, Althanstraße 14, Vienna, 1090, Austria

    Victoria Klang, Julia C. Schwarz & Claudia Valenta

Authors
  1. Victoria Klang
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  2. Julia C. Schwarz
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  3. Claudia Valenta
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Corresponding authors

Correspondence to Victoria Klang or Claudia Valenta .

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Editors and Affiliations

  1. Apoteka "Beograd", Belgrade, Serbia

    Nina Dragicevic

  2. San Francisco, California, USA

    Howard I. Maibach

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Klang, V., Schwarz, J.C., Valenta, C. (2015). Nanoemulsions in Dermal Drug Delivery. In: Dragicevic, N., Maibach, H. (eds) Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-45013-0_18

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  • DOI: https://doi.org/10.1007/978-3-662-45013-0_18

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-45012-3

  • Online ISBN: 978-3-662-45013-0

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