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      Novel Gel Microemulsion as Topical Drug Delivery System for Curcumin in Dermatocosmetics

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          Abstract

          Gel microemulsion combines the advantages of the microemulsion, which can encapsulate, protect and deliver large quantities of active ingredients, and the gel, which is so appreciated in the cosmetic industry. This study aimed to develop and characterize new gel microemulsions suitable for topical cosmetic applications, using grape seed oil as the oily phase, which is often employed in pharmaceuticals, especially in cosmetics. The optimized microemulsion was formulated using Tween 80 and Plurol ® Diisostearique CG as a surfactant mix and ethanol as a co-solvent. Three different water-soluble polymers were selected in order to increase the viscosity of the microemulsion: Carbopol ® 980 NF, chitosan, and sodium hyaluronate salt. All used ingredients are safe, biocompatible and biodegradable. Curcumin was chosen as a model drug. The obtained systems were physico-chemically characterized by means of electrical conductivity, dynamic light scattering, polarized microscopy and rheometric measurements. Evaluation of the cytotoxicity was accomplished by MTT assay. In the final phase of the study, the release behavior of Curcumin from the optimized microemulsion and two gel microemulsions was evaluated. Additionally, mathematical models were applied to establish the kinetic release mechanism. The obtained gel microemulsions could be effective systems for incorporation and controlled release of the hydrophobic active ingredients.

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          Hyaluronic acid: A key molecule in skin aging

          Skin aging is a multifactorial process consisting of two distinct and independent mechanisms: intrinsic and extrinsic aging. Youthful skin retains its turgor, resilience and pliability, among others, due to its high content of water. Daily external injury, in addition to the normal process of aging, causes loss of moisture. The key molecule involved in skin moisture is hyaluronic acid (HA) that has unique capacity in retaining water. There are multiple sites for the control of HA synthesis, deposition, cell and protein association and degradation, reflecting the complexity of HA metabolism. The enzymes that synthesize or catabolize HA and HA receptors responsible for many of the functions of HA are all multigene families with distinct patterns of tissue expression. Understanding the metabolism of HA in the different layers of the skin and the interactions of HA with other skin components will facilitate the ability to modulate skin moisture in a rational manner.
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            Studies of curcumin and curcuminoids. XXVII. Cyclodextrin complexation: solubility, chemical and photochemical stability.

            Cyclodextrin complexes of the natural compound curcumin were prepared in order to improve the water solubility and the hydrolytic and photochemical stability of the compound. Complex formation resulted in an increase in water solubility at pH 5 by a factor of at least 10(4). The hydrolytic stability of curcumin under alkaline conditions was strongly improved by complex formation, while the photodecomposition rate was increased compared to a curcumin solution in organic solvents. The cavity size and the charge and bulkiness of the cyclodextrin side-chains influenced the stability constant for complexation and the degradation rate of the curcumin molecule.
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              Microemulsions as transdermal drug delivery vehicles.

              Microemulsions are clear, stable, isotropic mixtures of oil, water, and surfactant, frequently in combination with a cosurfactant. Microemulsions have been intensively studied during the last decades by many scientists and technologists because of their great potential in many food and pharmaceutical applications. The use of microemulsions is advantageous not only due to the facile and low cost preparation, but also because of the improved bioavailability. The increased absorption of drugs in topical applications is attributed to enhancement of penetration through the skin by the carrier. Saturated and unsaturated fatty acids serving as an oil phase are frequently used as penetration enhancers. The most popular enhancer is oleic acid. Other permeation enhancers commonly used in transdermal formulations are isopropyl myristate, isopropyl palmitate, triacetin, isostearylic isostearate, R(+)-limonene and medium chain triglycerides. The most popular among the enhancing permeability surfactants are phospholipids that have been shown to enhance drug permeation in a different mode. l-alpha-phosphatidylcholine from egg yolk, l-alpha-phosphatidylcholine 60%, from soybean and dioleylphosphatidyl ethanolamine which are in a fluid state may diffuse into the stratum corneum and enhance dermal and transdermal drug penetration, while distearoylphosphatidyl choline which is in a gel-state has no such capability. Other very commonly used surfactants are Tween 20, Tween 80, Span 20, Azone, Plurol Isostearique and Plurol Oleique. As cosurfactants commonly serve short-chain alkanols such as ethanol and propylene glycol. Long-chain alcohols, especially 1-butanol, are known for their enhancing activity as well. Decanol was found to be an optimum enhancer among other saturated fatty alcohols that were examined (from octanol to myristyl alcohol). Many enhancers are concentration-dependent; therefore, optimal concentration for effective promotion should be determined. The delivery rate is dependent on the type of the drug, the structure and ingredients of the carrier, and on the character of the membrane in use. Each formulation should be examined very carefully, because every membrane alters the mechanism of penetration and can turn an enhancer to a retarder. Various potential mechanisms to enhance drug penetration through the skin include directly affecting the skin and modifying the formulation so the partition, diffusion, or solubility is altered. The combination of several enhancement techniques such as the use of iontophoresis with fatty acids leads to synergetic drug penetration and to decrease in skin toxicity. Selected studies of various microemulsions containing certain drugs including retinoic acid, 5-fluorouracil, triptolide, ascorbic acid, diclofenac, lidocaine, and prilocaine hydrochloride in transdermal formulations are presented in this review. In conclusion, microemulsions were found as an effective vehicle of the solubilization of certain drugs and as protecting medium for the entrapped of drugs from degradation, hydrolysis, and oxidation. It can also provide prolonged release of the drug and prevent irritation despite the toxicity of the drug. Yet, in spite of all the advantages the present formulations lack several key important characteristics such as cosmetic-permitted surfactants, free dilution in water capabilities, stability in the digestive tracts and sufficient solubilization capacity.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                07 April 2021
                April 2021
                : 13
                : 4
                : 505
                Affiliations
                [1 ]Polymer Department, National Institute for Research and Development in Chemistry and Petrochemistry-ICECHIM, 202 Spl. Independentei, 060021 Bucharest, Romania; scomoroscencocristina@ 123456gmail.com (C.S.); trica.bogdan@ 123456gmail.com (B.T.); claudia.ninciuleanu@ 123456yahoo.com (C.M.N.); lc_nistor@ 123456yahoo.com (C.L.N.); mihaescu_catalin96@ 123456yahoo.com (C.I.M.)
                [2 ]Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, 010737 Bucharest, Romania; mircea.teodorescu@ 123456upb.ro
                [3 ]Physical Chemistry Department, University of Bucharest, 030018 Bucharest, Romania; adina.raducan@ 123456g.unibuc.ro
                [4 ]Department of Biochemistry and Molecular Biology, Faculty of Biology, ICUB-Research Institute of the University of Bucharest, University of Bucharest, 050095 Bucharest, Romania; miruna.stan@ 123456bio.unibuc.ro (M.S.); sorina.voicu@ 123456bio.unibuc.ro (S.N.V.)
                Author notes
                Author information
                https://orcid.org/0000-0002-0333-911X
                https://orcid.org/0000-0002-7420-778X
                https://orcid.org/0000-0002-6273-8540
                https://orcid.org/0000-0002-9948-6914
                https://orcid.org/0000-0002-9200-5807
                https://orcid.org/0000-0002-0624-4626
                https://orcid.org/0000-0002-3317-2787
                Article
                pharmaceutics-13-00505
                10.3390/pharmaceutics13040505
                8067601
                33916981
                7fb61f92-e40d-463b-8483-41a788db3048
                © 2021 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 ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 27 February 2021
                : 04 April 2021
                Categories
                Article

                curcumin,gel microemulsion,transdermal delivery,microemulsion,dermatocosmetics,grape seed oil

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