Skip to main content

Advertisement

SpringerLink
Log in

Potential of Non-aqueous Microemulsions to Improve the Delivery of Lipophilic Drugs to the Skin

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

In this study, non-aqueous microemulsions were developed because of the challenges associated with finding pharmaceutically acceptable solvents for topical delivery of drugs sparingly soluble in water. The formulation irritation potential and ability to modulate the penetration of lipophilic compounds (progesterone, α-tocopherol, and lycopene) of interest for topical treatment/prevention of skin disorders were evaluated and compared to solutions and aqueous microemulsions of similar composition. The microemulsions (ME) were developed with BRIJ, vitamin E-TPGS, and ethanol as surfactant-co-surfactant blend and tributyrin, isopropyl myristate, and oleic acid as oil phase. As polar phase, propylene glycol (MEPG) or water (MEW) was used (26% w/w). The microemulsions were isotropic and based on viscosity and conductivity assessment, bicontinuous. Compared to drug solutions in lipophilic vehicles, MEPG improved drug delivery into viable skin layers by 2.5–38-fold; the magnitude of penetration enhancement mediated by MEPG into viable skin increased with drug lipophilicity, even though the absolute amount of drug delivered decreased. Delivery of progesterone and tocopherol, but not lycopene (the most lipophilic compound), increased up to 2.5-fold with MEW, and higher amounts of these two drugs were released from MEW (2–2.5-fold). Both microemulsions were considered safe for topical application, but MEPG-mediated decrease in the viability of reconstructed epidermis was more pronounced, suggesting its higher potential for irritation. We conclude that MEPG is a safe and suitable nanocarrier to deliver a variety of lipophilic drugs into viable skin layers, but the use of MEW might be more advantageous for drugs in the lower range of lipophilicity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Moniruzzaman M, Tamura M, Tahara Y, Kamiya N, Goto M. Ionic liquid-in-oil microemulsion as a potential carrier of sparingly soluble drug: characterization and cytotoxicity evaluation. Int J Pharm. 2010;400(1–2):243–50.

    Article  CAS  PubMed  Google Scholar 

  2. Lin CC, Yang CH, Chang NF, Wu PS, Chen YS, Lee SM, et al. Study on the stability of deoxyArbutin in an anhydrous emulsion system. Int J Mol Sci. 2011;12(9):5946–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Moser K, Kriwet K, Naik A, Kalia YN, Guy RH. Passive skin penetration enhancement and its quantification in vitro. Eur J Pharm Biopharm. 2001;52(2):103–12.

    Article  CAS  PubMed  Google Scholar 

  4. Cichewicz A, Pacleb C, Connors A, Hass MA, Lopes LB. Cutaneous delivery of alpha-tocopherol and lipoic acid using microemulsions: influence of composition and charge. J Pharm Pharmacol. 2013;65(6):817–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lopes LB. Overcoming the cutaneous barrier with microemulsions. Pharmaceutics. 2014;6(1):52–77.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Santos P, Watkinson AC, Hadgraft J, Lane ME. Application of microemulsions in dermal and transdermal drug delivery. Skin Pharmacol Physiol. 2008;21(5):246–59.

    Article  CAS  PubMed  Google Scholar 

  7. Zhang J, Michniak-Kohn B. Investigation of microemulsion microstructures and their relationship to transdermal permeation of model drugs: ketoprofen, lidocaine, and caffeine. Int J Pharm. 2011;421(1):34–44.

    Article  CAS  PubMed  Google Scholar 

  8. Pepe D, McCall M, Zheng H, Lopes LB. Protein transduction domain-containing microemulsions as cutaneous delivery systems for an anticancer agent. J Pharm Sci. 2013;102(5):1476–87.

    Article  CAS  PubMed  Google Scholar 

  9. Thomas S, Vieira CS, Hass MA, Lopes LB. Stability, cutaneous delivery, and antioxidant potential of a lipoic acid and alpha-tocopherol codrug incorporated in microemulsions. J Pharm Sci. 2014;103(8):2530–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lv FF, Zheng LQ, Tung CH. Phase behavior of the microemulsions and the stability of the chloramphenicol in the microemulsion-based ocular drug delivery system. Int J Pharm. 2005;301(1–2):237–46.

    Article  CAS  PubMed  Google Scholar 

  11. Hamill RD, Petersen RV. Effect of surfactant concentration on the interfacial viscosity of a nonaqueous system. J Pharm Sci. 1966;55(11):4.

    Google Scholar 

  12. Hamill R, Olson F, Petersen R. Some interfacial properties of a nonaqueous emulsion. J Pharm Sci. 1965;54(4):4.

    Article  Google Scholar 

  13. Suitthimeathegorn O, Jaitely V, Florence AT. Novel anhydrous emulsions: formulation as controlled release vehicles. Int J Pharm. 2005;298(2):367–71.

    Article  CAS  PubMed  Google Scholar 

  14. Atanase LI, Riess G. Block copolymer stabilized nonaqueous biocompatible sub-micron emulsions for topical applications. Int J Pharm. 2013;448(2):339–45.

    Article  CAS  PubMed  Google Scholar 

  15. Crespy D, Landfester K. Making dry fertile: a practical tour of non-aqueous emulsions and miniemulsions, their preparation and some applications. Soft Matter. 2011;7:11.

    Article  CAS  Google Scholar 

  16. Friberg E, Podzimek M. A non-aqueous microemulsion. Colloid Polym Sci. 1984;262(3):252–3.

    Article  CAS  Google Scholar 

  17. Harrar A, Zech O, Klaus A, Bauduin P, Kunz W. Influence of surfactant amphiphilicity on the phase behavior of IL-based microemulsions. J Colloid Interface Sci. 2011;362(2):423–9.

    Article  CAS  PubMed  Google Scholar 

  18. Charoenputtakun P, Li SK, Ngawhirunpat T. Iontophoretic delivery of lipophilic and hydrophilic drugs from lipid nanoparticles across human skin. Int J Pharm. 2015;495(1):318–28.

    Article  CAS  PubMed  Google Scholar 

  19. Magnusson BM, Cross SE, Winckle G, Roberts MS. Percutaneous absorption of steroids: determination of in vitro permeability and tissue reservoir characteristics in human skin layers. Skin Pharmacol Physiol. 2006;19(6):336–42.

    Article  CAS  PubMed  Google Scholar 

  20. Toropainen E, Ranta VP, Talvitie A, Suhonen P, Urtti A. Culture model of human corneal epithelium for prediction of ocular drug absorption. Invest Ophthalmol Vis Sci. 2001;42(12):2942–8.

    CAS  PubMed  Google Scholar 

  21. Mukai K, Tokunaga A, Itoh S, Kanesaki Y, Ohara K, Nagaoka S, et al. Structure-activity relationship of the free-radical-scavenging reaction by vitamin E (alpha-, beta-, gamma-, delta-Tocopherols) and ubiquinol-10: pH dependence of the reaction rates. J Phys Chem B. 2007;111(3):652–62.

    Article  CAS  PubMed  Google Scholar 

  22. Teichmann A, Jacobi U, Ossadnik M, Richter H, Koch S, Sterry W, et al. Differential stripping: determination of the amount of topically applied substances penetrated into the hair follicles. J Invest Dermatol. 2005;125(2):264–9.

    Article  CAS  PubMed  Google Scholar 

  23. Spernath A, Yaghmur A, Aserin A, Hoffman RE, Garti N. Food-grade microemulsions based on nonionic emulsifiers: media to enhance lycopene solubilization. J Agric Food Chem. 2002;50(23):6917–22.

    Article  CAS  PubMed  Google Scholar 

  24. Vertzoni M, Kartezini T, Reppas C, Archontaki H, Valsami G. Solubilization and quantification of lycopene in aqueous media in the form of cyclodextrin binary systems. Int J Pharm. 2006;309(1–2):115–22.

    Article  CAS  PubMed  Google Scholar 

  25. Poljsak B, Dahmane R. Free radicals and extrinsic skin aging. Dermatol Res Pract. 2012;2012:135206.

    Article  PubMed  PubMed Central  Google Scholar 

  26. van Breemen RB, Pajkovic N. Multitargeted therapy of cancer by lycopene. Cancer Lett. 2008;269(2):339–51.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Ascenso A, Pinho S, Eleuterio C, Praca FG, Bentley MV, Oliveira H, et al. Lycopene from tomatoes: vesicular nanocarrier formulations for dermal delivery. J Agric Food Chem. 2013;61(30):7284–93.

    Article  CAS  PubMed  Google Scholar 

  28. Routley CE, Ashcroft GS. Effect of estrogen and progesterone on macrophage activation during wound healing. Wound repair and regeneration: official publication of the Wound Healing Society [and] the European Tissue Repair Society. 2009;17(1):42–50.

  29. Kantarci G, Ozguney I, Karasulu HY, Arzik S, Guneri T. Comparison of different water/oil microemulsions containing diclofenac sodium: preparation, characterization, release rate, and skin irritation studies. AAPS PharmSciTech. 2007;8(4), E91.

    Article  PubMed  Google Scholar 

  30. Lopes LB, Murphy N, Nornoo A. Enhancement of transdermal delivery of progesterone using medium-chain mono and diglycerides as skin penetration enhancers. Pharm Dev Technol. 2009;14(5):524–9.

    Article  CAS  PubMed  Google Scholar 

  31. Hosmer J, Reed R, Bentley MV, Nornoo A, Lopes LB. Microemulsions containing medium-chain glycerides as transdermal delivery systems for hydrophilic and hydrophobic drugs. AAPS PharmSciTech. 2009;10(2):589–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Nornoo AO, Chow DS. Cremophor-free intravenous microemulsions for paclitaxel II. Stability, in vitro release and pharmacokinetics. Int J Pharm. 2008;349(1–2):117–23.

    Article  CAS  PubMed  Google Scholar 

  33. Jordan M, Nayel A, Brownlow B, Elbayoumi T. Development and evaluation of tocopherol-rich argan oil-based nanoemulsions as vehicles possessing anticancer activity. J Biomed Nanotechnol. 2012;8(6):944–56.

    Article  CAS  PubMed  Google Scholar 

  34. Pierre MB, Ricci Jr E, Tedesco AC, Bentley MV. Oleic acid as optimizer of the skin delivery of 5-aminolevulinic acid in photodynamic therapy. Pharm Res. 2006;23(2):360–6.

    Article  CAS  PubMed  Google Scholar 

  35. Patel N, Schmid U, Lawrence MJ. Phospholipid-based microemulsions suitable for use in foods. J Agric Food Chem. 2006;54(20):7817–24.

    Article  CAS  PubMed  Google Scholar 

  36. Hosmer JM, Steiner AA, Lopes LB. Lamellar liquid crystalline phases for cutaneous delivery of Paclitaxel: impact of the monoglyceride. Pharm Res. 2013;30(3):694–706.

    Article  CAS  PubMed  Google Scholar 

  37. Hosmer JM, Shin SH, Nornoo A, Zheng H, Lopes LB. Influence of internal structure and composition of liquid crystalline phases on topical delivery of paclitaxel. J Pharm Sci. 2011;100(4):1444–55.

    Article  CAS  PubMed  Google Scholar 

  38. Clogston J, Rathman J, Tomasko D, Walker H, Caffrey M. Phase behavior of a monoacylglycerol: (myverol 18-99K)/water system. Chem Phys Lipids. 2000;107(2):191–220.

    Article  CAS  PubMed  Google Scholar 

  39. Shah JC, Sadhale Y, Chilukuri DM. Cubic phase gels as drug delivery systems. Adv Drug Deliv Rev. 2001;47(2–3):229–50.

    Article  CAS  PubMed  Google Scholar 

  40. Wang Z, Diao Z, Liu F, Li G, Zhang G. Microstructure and rheological properties of liquid crystallines formed in Brij 97/water/IPM system. J Colloid Interface Sci. 2006;297(2):813–8.

    Article  CAS  PubMed  Google Scholar 

  41. Pepe D, Phelps J, Lewis K, Dujack J, Scarlett K, Jahan S, et al. Decylglucoside-based microemulsions for cutaneous localization of lycopene and ascorbic acid. Int J Pharm. 2012;434(1–2):420–8.

    Article  CAS  PubMed  Google Scholar 

  42. Garti N, Yaghmur A, Leser ME, Clement V, Watzke HJ. Improved oil solubilization in oil/water food grade microemulsions in the presence of polyols and ethanol. J Agric Food Chem. 2001;49(5):2552–62.

    Article  CAS  PubMed  Google Scholar 

  43. Kogan A, Aserin A, Garti N. Improved solubilization of carbamazepine and structural transitions in nonionic microemulsions upon aqueous phase dilution. J Colloid Interface Sci. 2007;315(2):637–47.

    Article  CAS  PubMed  Google Scholar 

  44. Kogan A, Garti N. Microemulsions as transdermal drug delivery vehicles. Adv Colloid Interface Sci. 2006;123–126:369–85.

    Article  PubMed  CAS  Google Scholar 

  45. Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery systems. Adv Drug Deliv Rev. 2000;45(1):89–121.

    Article  CAS  PubMed  Google Scholar 

  46. Heuschkel S, Goebel A, Neubert RH. Microemulsions--modern colloidal carrier for dermal and transdermal drug delivery. J Pharm Sci. 2008;97(2):603–31.

    Article  CAS  PubMed  Google Scholar 

  47. Kreilgaard M. Influence of microemulsions on cutaneous drug delivery. Adv Drug Deliv Rev. 2002;54 Suppl 1:S77–98.

    Article  CAS  PubMed  Google Scholar 

  48. Graf A, Ablinger E, Peters S, Zimmer A, Hook S, Rades T. Microemulsions containing lecithin and sugar-based surfactants: nanoparticle templates for delivery of proteins and peptides. Int J Pharm. 2008;350(1–2):351–60.

    Article  CAS  PubMed  Google Scholar 

  49. Krauel K, Graf A, Hook SM, Davies NM, Rades T. Preparation of poly (alkylcyanoacrylate) nanoparticles by polymerization of water-free microemulsions. J Microencapsul. 2006;23(5):499–512.

    Article  CAS  PubMed  Google Scholar 

  50. Mahdi ES, Noor AM, Sakeena MH, Abdullah GZ, Abdulkarim MF, Sattar MA. Formulation and in vitro release evaluation of newly synthesized palm kernel oil esters-based nanoemulsion delivery system for 30% ethanolic dried extract derived from local Phyllanthus urinaria for skin antiaging. Int J Nanomedicine. 2011;6:2499–512.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Lopes LB, VanDeWall H, Li HT, Venugopal V, Li HK, Naydin S, et al. Topical delivery of lycopene using microemulsions: enhanced skin penetration and tissue antioxidant activity. J Pharm Sci. 2010;99(3):1346–57.

    Article  CAS  PubMed  Google Scholar 

  52. Herwadkar A, Sachdeva V, Taylor LF, Silver H, Banga AK. Low frequency sonophoresis mediated transdermal and intradermal delivery of ketoprofen. Int J Pharm. 2012;423(2):289–96.

    Article  CAS  PubMed  Google Scholar 

  53. Mohammed D, Hirata K, Hadgraft J, Lane ME. Influence of skin penetration enhancers on skin barrier function and skin protease activity. Eur J Pharm Sci. 2014;51:118–22.

    Article  CAS  PubMed  Google Scholar 

  54. Alber C, Buraczewska-Norin I, Kocherbitov V, Saleem S, Loden M, Engblom J. Effects of water activity and low molecular weight humectants on skin permeability and hydration dynamics - a double-blind, randomized and controlled study. Int J Cosmet Sci. 2014;36(5):412–8.

    Article  CAS  PubMed  Google Scholar 

  55. Rozman B, Zvonar A, Falson F, Gasperlin M. Temperature-sensitive microemulsion gel: an effective topical delivery system for simultaneous delivery of vitamins C and E. AAPS PharmSciTech. 2009;10(1):54–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Rangarajan M, Zatz JL. Effect of formulation on the topical delivery of alpha-tocopherol. J Cosmet Sci. 2003;54(2):161–74.

    CAS  PubMed  Google Scholar 

  57. Kandárová H, Hayden P, Klausner M, Kubilus J, Sheasgreen J. An in vitro skin irritation test (SIT) using the EpiDerm Reconstructed Human Epidermal (RHE) model. J Visual Exp. 2009;29. http://www.jove.com/index/Details.stp?ID=1366. doi: 10.3791/1366.

  58. Brohem CA, Cardeal LB, Tiago M, Soengas MS, Barros SB, Maria-Engler SS. Artificial skin in perspective: concepts and applications. Pigment Cell Melanoma Res. 2011;24(1):35–50.

    Article  PubMed  Google Scholar 

  59. Rozman B, Gosenca M, Falson F, Gasperlin M. The influence of microemulsion structure on their skin irritation and phototoxicity potential. Int J Pharm. 2016;499(1–2):228–35.

    Article  CAS  PubMed  Google Scholar 

  60. Hathout RM, Woodman TJ, Mansour S, Mortada ND, Geneidi AS, Guy RH. Microemulsion formulations for the transdermal delivery of testosterone. Eur J Pharm Sci. 2010;40(3):188–96.

    Article  CAS  PubMed  Google Scholar 

  61. Podlogar F, Gasperlin M, Tomsic M, Jamnik A, Rogac MB. Structural characterisation of water-Tween 40/Imwitor 308-isopropyl myristate microemulsions using different experimental methods. Int J Pharm. 2004;276(1–2):115–28.

    Article  CAS  PubMed  Google Scholar 

  62. Todosijevic MN, Savic MM, Batinic BB, Markovic BD, Gasperlin M, Randelovic DV, et al. Biocompatible microemulsions of a model NSAID for skin delivery: a decisive role of surfactants in skin penetration/irritation profiles and pharmacokinetic performance. Int J Pharm. 2015;496(2):931–41.

    Article  CAS  PubMed  Google Scholar 

  63. Kogan A, Shalev DE, Raviv U, Aserin A, Garti N. Formation and characterization of ordered bicontinuous microemulsions. J Phys Chem B. 2009;113(31):10669–78.

    Article  CAS  PubMed  Google Scholar 

  64. Malheiro AR, Varanda LC, Perez J, Villullas HM. The aerosol OT+n-butanol+n-heptane+water system: phase behavior, structure characterization, and application to Pt70Fe30 nanoparticle synthesis. Langmuir. 2007;23(22):11015–20.

    Article  CAS  PubMed  Google Scholar 

  65. Gee CM, Nicolazzo JA, Watkinson AC, Finnin BC. Assessment of the lateral diffusion and penetration of topically applied drugs in humans using a novel concentric tape stripping design. Pharm Res. 2012;29(8):2035–46.

    Article  CAS  PubMed  Google Scholar 

  66. Lopes LB, Reed R. A simple and rapid method to assess lycopene in multiple layers of skin samples. Biomed Chromatogr. 2010;24(2):154–9.

    CAS  PubMed  Google Scholar 

  67. Mahrhauser D, Nagelreiter C, Baierl A, Skipiol J, Valenta C. Influence of a multiple emulsion, liposomes and a microemulsion gel on sebum, skin hydration and TEWL. Int J Cosmet Sci. 2015;37(2):181–6.

    Article  CAS  PubMed  Google Scholar 

  68. Herkenne C, Naik A, Kalia YN, Hadgraft J, Guy RH. Effect of propylene glycol on ibuprofen absorption into human skin in vivo. J Pharm Sci. 2008;97(1):185–97.

    Article  CAS  PubMed  Google Scholar 

  69. Williams AC, Barry BW. Penetration enhancers. Adv Drug Deliv Rev. 2004;56(5):603–18.

    Article  CAS  PubMed  Google Scholar 

  70. Khandavilli S, Panchagnula R. Nanoemulsions as versatile formulations for paclitaxel delivery: peroral and dermal delivery studies in rats. J Invest Dermatol. 2007;127(1):154–62.

    Article  CAS  PubMed  Google Scholar 

  71. Bernabeu E, Gonzalez L, Cagel M, Gergic EP, Moretton MA, Chiappetta DA. Novel Soluplus((R))-TPGS mixed micelles for encapsulation of paclitaxel with enhanced in vitro cytotoxicity on breast and ovarian cancer cell lines. Colloids Surf B: Biointerfaces. 2016;140:403–11.

    Article  CAS  PubMed  Google Scholar 

  72. Wartewig S, Neubert RH. Properties of ceramides and their impact on the stratum corneum structure: a review. Part 1: ceramides. Skin Pharmacol Physiol. 2007;20(5):220–9.

    Article  CAS  PubMed  Google Scholar 

  73. Wagner H, Kostka KH, Adelhardt W, Schaefer UF. Effects of various vehicles on the penetration of flufenamic acid into human skin. Eur J Pharm Biopharm. 2004;58(1):121–9.

    Article  CAS  PubMed  Google Scholar 

  74. Cal K. Skin penetration of terpenes from essential oils and topical vehicles. Planta Med. 2006;72(4):311–6.

    Article  CAS  PubMed  Google Scholar 

  75. Avdeef A, Bendels S, Tsinman O, Tsinman K, Kansy M. Solubility-excipient classification gradient maps. Pharm Res. 2007;24(3):530–45.

    Article  CAS  PubMed  Google Scholar 

  76. El Maghraby GM. Occlusive and non-occlusive application of microemulsion for transdermal delivery of progesterone: mechanistic studies. Sci Pharm. 2012;80(3):765–78.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Dubbs MD, Gupta RB, 590. Solubility of vitamin E (a-Tocopherol) and vitamin K3 (Menadione) in ethanol-water mixture. J Chem Eng Data. 1998;43(590):2.

    Google Scholar 

  78. Djekic L, Martinovic M, Stepanovic-Petrovic R, Tomic M, Micov A, Primorac M. Design of block copolymer costabilized nonionic microemulsions and their in vitro and in vivo assessment as carriers for sustained regional delivery of ibuprofen via topical administration. J Pharm Sci. 2015;104(8):2501–12.

    Article  CAS  PubMed  Google Scholar 

  79. Cavalcanti AL, Reis MY, Silva GC, Ramalho IM, Guimaraes GP, Silva JA, et al. Microemulsion for topical application of pentoxifylline: in vitro release and in vivo evaluation. Int J Pharm. 2016;506(1–2):351–60.

    Article  CAS  PubMed  Google Scholar 

  80. Erdal MS, Ozhan G, Mat MC, Ozsoy Y, Gungor S. Colloidal nanocarriers for the enhanced cutaneous delivery of naftifine: characterization studies and in vitro and in vivo evaluations. Int J Nanomedicine. 2016;11:1027–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Mishra R, Prabhavalkar KS, Bhatt LK. Preparation, optimization, and evaluation of Zaltoprofen-loaded microemulsion and microemulsion-based gel for transdermal delivery. J Liposome Res. 2016:1–10.

  82. Sharma G, Dhankar G, Thakur K, Raza K, Katare OP. Benzyl benzoate-loaded microemulsion for topical applications: enhanced dermatokinetic profile and better delivery promises. AAPS PharmSciTech; 2015.

  83. Nasr M, Abdel-Hamid S. Optimizing the dermal accumulation of a tazarotene microemulsion using skin deposition modeling. Drug Dev Ind Pharm. 2016;42(4):636–43.

    CAS  PubMed  Google Scholar 

  84. Zhao L, Wang Y, Zhai Y, Wang Z, Liu J, Zhai G. Ropivacaine loaded microemulsion and microemulsion-based gel for transdermal delivery: preparation, optimization, and evaluation. Int J Pharm. 2014;477(1–2):47–56.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by São Paulo Research Foundation (FAPESP grant#2013/16617-7) and PhRMA Foundation (Research Starter Grant in Pharmaceutics). Fellowships from CAPES (V. Carvalho) and FAPESP (D. de Lemos and A. Migotto) are greatly appreciated. We would like to thank Dr. A. Steiner for critical comments on the manuscript.

Author information

Author notes

    Authors and Affiliations

    1. Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1524, São Paulo, São Paulo, Brazil

      Vanessa F. Carvalho, Debora P. de Lemos, Camila S. Vieira, Amanda Migotto & Luciana B. Lopes

    2. Albany College of Pharmacy and Health Sciences, Albany, New York, USA

      Luciana B. Lopes

    Authors
    1. Vanessa F. Carvalho
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Debora P. de Lemos
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Camila S. Vieira
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Amanda Migotto
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Luciana B. Lopes
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Luciana B. Lopes.

    Additional information

    Vanessa F. Carvalho and Debora P. de Lemos contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Carvalho, V.F., de Lemos, D.P., Vieira, C.S. et al. Potential of Non-aqueous Microemulsions to Improve the Delivery of Lipophilic Drugs to the Skin. AAPS PharmSciTech 18, 1739–1749 (2017). https://doi.org/10.1208/s12249-016-0643-7

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1208/s12249-016-0643-7

    KEY WORDS

    Search

    Navigation