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      Topical Nano and Microemulsions for Skin Delivery

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          Abstract

          Nanosystems such as microemulsions (ME) and nanoemulsions (NE) offer considerable opportunities for targeted drug delivery to and via the skin. ME and NE are stable colloidal systems composed of oil and water, stabilised by a mixture of surfactants and cosurfactants, that have received particular interest as topical skin delivery systems. There is considerable scope to manipulate the formulation components and characteristics to achieve optimal bioavailability and minimal skin irritancy. This includes the incorporation of established chemical penetration enhancers to fluidize the stratum corneum lipid bilayers, thus reducing the primary skin barrier and increasing permeation. This review discusses nanosystems with utility in skin delivery and focuses on the composition and characterization of ME and NE for topical and transdermal delivery. The mechanism of skin delivery across the stratum corneum and via hair follicles is reviewed with particular focus on the influence of formulation.

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          Most cited references 95

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          Penetration enhancers.

          One long-standing approach for improving transdermal drug delivery uses penetration enhancers (also called sorption promoters or accelerants) which penetrate into skin to reversibly decrease the barrier resistance. Numerous compounds have been evaluated for penetration enhancing activity, including sulphoxides (such as dimethylsulphoxide, DMSO), Azones (e.g. laurocapram), pyrrolidones (for example 2-pyrrolidone, 2P), alcohols and alkanols (ethanol, or decanol), glycols (for example propylene glycol, PG, a common excipient in topically applied dosage forms), surfactants (also common in dosage forms) and terpenes. Many potential sites and modes of action have been identified for skin penetration enhancers; the intercellular lipid matrix in which the accelerants may disrupt the packing motif, the intracellular keratin domains or through increasing drug partitioning into the tissue by acting as a solvent for the permeant within the membrane. Further potential mechanisms of action, for example with the enhancers acting on desmosomal connections between corneocytes or altering metabolic activity within the skin, or exerting an influence on the thermodynamic activity/solubility of the drug in its vehicle are also feasible, and are also considered in this review.
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            Ethosomes - novel vesicular carriers for enhanced delivery: characterization and skin penetration properties.

            This work describes a novel carrier for enhanced skin delivery, the ethosomal system, which is composed of phospholipid, ethanol and water. Ethosomal systems were much more efficient at delivering a fluorescent probe to the skin in terms of quantity and depth, than either liposomes or hydroalcoholic solution. The ethosomal system dramatically enhanced the skin permeation of minoxidil in vitro compared with either ethanolic or hydroethanolic solution or phospholipid ethanolic micellar solution of minoxidil. In addition, the transdermal delivery of testosterone from an ethosomal patch was greater both in vitro and in vivo than from commercially available patches. Skin permeation of ethosomal components, ethanol and phospholipid, was demonstrated in diffusion-cell experiments. Ethosomal systems composed of soy phosphatidylcholine 2%, ethanol 30% and water were shown by electron microscopy to contain multilamellar vesicles. 31P-NMR studies confirmed the bilayer configuration of the lipids. Calorimetry and fluorescence measurements suggested that the vesicular bilayers are flexible, having a relatively low T(m) and fluorescence anisotropy compared with liposomes obtained in the absence of ethanol. Dynamic light scattering measurements indicated that ethanol imparted a negative charge to the vesicles. The average vesicle size, as measured by dynamic light scattering, was modulated by altering the ethosome composition. Experiments using fluorescent probes and ultracentrifugation showed that the ethosomes had a high entrapment capacity for molecules of various lyophilicities.
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              Design and production of nanoparticles formulated from nano-emulsion templates-a review.

              A considerable number of nanoparticle formulation methods are based on nano-emulsion templates, which in turn are generated in various ways. It must therefore be taken into account that active principles and drugs encapsulated in nanoparticles can potentially be affected by these nano-emulsion formulation processes. Such potential differences may include drug sensitivity to temperature, high-shear devices, or even contact with organic solvents. Likewise, nano-emulsion formulation processes must be chosen in function of the selected therapeutic goals of the nano-carrier suspension and its administration route. This requires the nanoparticle formulation processes (and thus the nano-emulsion formation methods) to be more adapted to the nature of the encapsulated drugs, as well as to the chosen route of administration. Offering a comprehensive review, this paper proposes a link between nano-emulsion formulation methods and nanoparticle generation, while at the same time bearing in mind the above-mentioned parameters for active molecule encapsulation. The first part will deal with the nano-emulsion template through the different formulation methods, i.e. high energy methods on the one hand, and low-energy ones (essentially spontaneous emulsification and the phase inversion temperature (PIT) method) on the other. This will be followed by a review of the different families of nanoparticles (i.e. polymeric or lipid nanospheres and nanocapsules) highlighting the links (or potential links) between these nanoparticles and the different nano-emulsion formulation methods upon which they are based.
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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                21 September 2017
                December 2017
                : 9
                : 4
                Affiliations
                [1 ]School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, G.P.O. Box U1987, Perth, WA 6845, Australia; c.nastiti@ 123456postgrad.curtin.edu.au (C.M.R.R.N.); thellie.ponto@ 123456postgrad.curtin.edu.au (T.P.); H.Benson@ 123456curtin.edu.au (H.A.E.B.)
                [2 ]Faculty of Pharmacy, Sanata Dharma University, Yogyakarta 55282, Indonesia
                [3 ]Therapeutics Research Centre, The University of Queensland Diamentina Institute, Faculty of Medicine, Translational Research Institute, Woolloongabba, QLD 4102, Australia; e.abd@ 123456uq.edu.au (E.A.); jeff.grice@ 123456uq.edu.au (J.E.G.)
                [4 ]School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia
                Author notes
                [* ]Correspondence: m.roberts@ 123456uq.edu.au ; Tel.: +61-7-34438031; Fax: +61-7-34437779
                [†]

                These authors contributed equally to this work.

                Article
                pharmaceutics-09-00037
                10.3390/pharmaceutics9040037
                5750643
                28934172
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

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