title: Potential of Non-aqueous Microemulsions to Improve the Delivery of Lipophilic Drugs to the Skin.
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.
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1524, São Paulo, São Paulo, Brazil.
authors.forename: Vanessa F
authors.initials: VF
authors.lastname: Carvalho
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1524, São Paulo, São Paulo, Brazil.
authors.forename: Debora P
authors.initials: DP
authors.lastname: de Lemos
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1524, São Paulo, São Paulo, Brazil.
authors.forename: Camila S
authors.initials: CS
authors.lastname: Vieira
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1524, São Paulo, São Paulo, Brazil.
authors.forename: Amanda
authors.initials: A
authors.lastname: Migotto
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1524, São Paulo, São Paulo, Brazil. lublopes@usp.br.|Albany College of Pharmacy and Health Sciences, Albany, New York, USA. lublopes@usp.br.
authors.forename: Luciana B
authors.initials: LB
authors.lastname: Lopes
mesh_terms: D000279:Administration, Cutaneous; D000287:Administration, Topical; D000818:Animals; D002338:Carotenoids / Q000008:administration & dosage / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions / Q000008:administration & dosage; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D008055:Lipids / Q000008:administration & dosage; D000077276:Lycopene; D019946:Propylene Glycol / Q000008:administration & dosage / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology; D013501:Surface-Active Agents / Q000008:administration & dosage* / Q000378:metabolism; D013552:Swine; D014783:Viscosity; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D004655:Emulsions; D008055:Lipids; D013501:Surface-Active Agents; D002338:Carotenoids; D019946:Propylene Glycol; D024502:alpha-Tocopherol; D000077276:Lycopene
keywords: lipophilic drugs; microemulsion; skin; transdermal