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No / A novel approach for identifying synergistic mixtures of skin penetration enhancers promises to transform development of transdermal products, including patches.

The objective of this research is the development of an electrically active microneedle array that can deliver biomolecules such as DNA and drugs to epidermal cells by means of electroporation. Properly metallized microneedles could serve as microelectrodes essential for electroporation. Furthermore, the close needle-to-needle spacing of microneedle electrodes provides the advantage of utilizing reduced voltage, which is essential for safety as well as portable applications, while maintaining the large electric fields required for electroporation. Therefore, microneedle arrays can potentially be used as part of a minimally invasive, highly-localized electroporation system for cells in the epidermis layer of the skin. This research consists of three parts: development of the 3-D microfabrication technology to create the microneedle array, fabrication and characterization of the microneedle array, and the electroporation studies performed with the microneedle array. A 3-D fabrication process was developed to produce a microneedle array using an inclined UV exposure technique combined with micromolding technology, potentially enabling low cost mass-manufacture. The developed technology is also capable of fabricating 3-D microstructures of various heights using a single mask. The fabricated microneedle array was then tested to demonstrate its feasibility for through-skin electrical and mechanical functionality using a skin insertion test. It was found that the microneedles were able to penetrate skin without breakage. To study the electrical properties of the array, a finite element simulation was performed to examine the electric field distribution. From these simulation results, a predictive model was constructed to estimate the effective volume for electroporation. Finally, studies to determine hemoglobin release from bovine red blood cells (RBC) and the delivery of molecules such as calcein and bovine serum albumin (BSA) into human prostate cancer cells were used to verify the electrical functionality of this device. This work established that this device can be used to lyse RBC and to deliver molecules, e.g. calcein, into cells, thus supporting our contention that this metallized microneedle array can be used to perform electroporation at reduced voltage. Further studies to show efficacy in skin should now be performed.

Submitted by Marco Antonio Oliveira da Silva (maosilva@ipen.br) on 2017-11-09T11:05:48Z No. of bitstreams: 0 / Made available in DSpace on 2017-11-09T11:05:48Z (GMT). No. of bitstreams: 0 / Cuidar de feridas é um processo dinâmico e complexo que requer atenção especial principalmente quando se refere a uma lesão crônica. A lesão por pressão (LPP) é uma ferida crônica localizada na pele ou no tecido subjacente, geralmente sobre uma proeminência óssea, resultante de pressão isolada ou pressão combinada com fricção ou cisalhamento. O objetivo foi avaliar a aplicabilidade das membranas de hidrogel com nanopartículas de prata no tratamento de lesões por pressão (LPPs) em usuários do SUS, por meio de protocolo clínico. O projeto da pesquisa foi aprovado pelo Comitê de Ética em Pesquisa da UFT/TO sob nº 161/2013, e foram seguidos todos os preceitos éticos conforme Resolução 466/12 do CNS do Ministério da Saúde. Trata-se de um estudo de intervenção terapêutica, do tipo ensaio clínico não controlado, sobre a avaliação do uso da membrana de hidrogel com nanopartículas de prata (NPAg) produzida pelo Instituto de Pesquisa em Energia Nuclear (IPEN). A população do estudo foi composta por 19 pacientes, que por critérios de inclusão e exclusão foi constituída por uma amostra de 6 (seis) pacientes de ambos os gêneros, internados no Hospital de Referência de Porto Nacional, no período de janeiro de 2014 a dezembro de 2015, acometidos por lesões por pressão categoria 3, 4 e não classificável. O estudo apresentou como limitações o restrito número de pacientes por amostra, por se tratar de pesquisa clínica experimental, com um grupo investigado altamente selecionado pelos critérios de exclusão e inclusão. Os hidogéis com NPAg, produzidos pelo IPEN, mostraram-se eficazes no tratamento das LPPs, pois proporcionaram a ferida condições para a epitelização. Houve diminuição do odor, dos tecidos desvitalizados e da dor, itens estes que quando presentes retardam a cicatrização. Porém são necessários novos estudos, envolvendo estes curativos com um número maior de pacientes. / Dissertação (Mestrado em Tecnologia Nuclear) / IPEN/D / Instituto de Pesquisas Energéticas e Nucleares - IPEN-CNEN/SP

Orientadores: Eneida de Paula, Michelle Franz Montan Braga Leite / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-21T07:56:47Z (GMT). No. of bitstreams: 1 Sobral_VivianeRobertaVieira_M.pdf: 3065834 bytes, checksum: 821d44f8c5c07441498c0b9a0426b822 (MD5) Previous issue date: 2012 / Resumo: Benzocaína (BZC) é um anestésico local do tipo éster usado principalmente em formulações de uso tópico, dérmico ou em mucosas. Em estudos anteriores de nosso laboratório, a interação da BZC com lipossomas convencionais compostos de fosfatidilcolina de ovo, colesterol e alfa-tocoferol foi caracterizada. No entanto, estudos recentes têm demonstrado que lipossomas elásticos, preparados com adição de um tensoativo, apresentam vantagens em relação aos convencionais, pois conseguem atravessar de maneira mais eficiente o estrato córneo. O objetivo deste trabalho foi avaliar e caracterizar, sob o aspecto físico-químico e farmacêutico, diferentes formulações em gel de benzocaína: BZC a 10% e 20%, BZC a 10% encapsulada em lipossomas convencionais (LC) ou lipossomas elásticos (LE) e formulação comercial (contendo BZC a 20%). A quantificação do teor de benzocaína nas formulações foi realizada através de cromatografia líquida de alta eficiência e validada segundo o Guia de Validação de Métodos Analíticos e Bioanalíticos (Brasil, 2003). Em estudos de estabilidade acelerada (Brasil, 2005) foram avaliados: peroxidação lipídica, pH, teor e comportamento reológico das formulações. As formulações recém-preparadas foram avaliadas também quanto à citotoxicidade, liberação e permeação in vitro. Todas as formulações mostraram-se estáveis por até 6 meses, com pequenas variações de pH e teor; a peroxidação lipídica aumentou ao final deste período, porém a quantidade de peróxidos formados não ultrapassou 1% do total de lipídios presentes na formulação.... Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da tese digital / Abstract: Benzocaine (BZC) is an ester type local anesthetic mainly used in topical formulations for either dermal or mucosa. In previous studies from our laboratory, the interaction of BZC with conventional liposomes composed of egg phosphatidylcholine, cholesterol and alpha-tocopherol was characterized. However, recent studies have demonstrated that elastic liposomes prepared with the addition of a surfactant, show advantages over conventional vesicles, as they can effectively cross the stratum corneum. The objective of this study was to evaluate and characterize the physicochemical and pharmaceutical aspects of different gel formulations of BZC: 10% and 20% of BZC, 10% BZC encapsulated into conventional (CL) or elastic liposomes (EL) and commercial formulation (containing 20% BZC). The quantification of BZC in the formulations was performed by high performance liquid chromatography (HPLC) and validated according to the Guide for Validation of Analytical and Bioanalytical Methods (Brazil, 2003). Accelerated stability studies (Brazil, 2005) were used to evaluate lipid peroxidation, pH, and rheological behavior of the formulations. The freshly prepared formulations were submitted to cytotoxicity and in vitro release tests. All formulations were stable up to 6 months, with minor variations in pH and content of BZC; although the lipid peroxidation increased at the end of that period, the amount of peroxides produced was less than 1% of the total lipids in the formulation. ... Note: The complete abstract is available with the full electronic digital thesis or dissertations / Mestrado / Bioquimica / Mestre em Biologia Funcional e Molecular

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Thesis (MScMed (Pharmacology))--University of Stellenbosch, 2005. / During the last two decades the effects of ultrasound on the transdermal diffusion of a wide variety of drugs have been extensively investigated. Because there is much uncertainty regarding the efficacy of and mechanisms involved in this mode of permeation enhancement, the objective of the study was to investigate the effect of ultrasound on the transdermal permeation of the nonsteroidal anti-inflammatory drug, diclofenac. For this purpose a dual-stage experimental design and a continuous flow-through diffusion system was used. Therapeutic levels of continuous ultrasound of 3 MHz at an intensity of 2 W/cm2 for 10 min, were used. It was clear from the present study that ultrasound enhanced the permeability of human skin to diclofenac released from a commercially available gel. These results were in contrast with those obtained for ibuprofen in an in vitro study across human skin, but in agreement with those obtained in two in vivo studies of the latter nonsteroidal anti-inflammatory drug. Steady state flux values of diclofenac remained approximately 1.26 times higher than those of controls during the 24 h of the experiment. These observations concurred with those made in two previous in vivo studies. Furthermore, the in vitro flow-through diffusion model was shown to have predictive value as an in vivo method for sonophoresis. Temperature-dependent flux rates for 3H2O across human skin were also studied. The mechanistic effects of ultrasound on the permeability characteristics of human skin have been reported on in a number of studies. Although various mechanisms have been proposed, there is no consensus regarding their relative importance. In addition the temperature-dependent flux changes of 3H2O across human skin were investigated using a continuous flow-through diffusion system. The same ultrasound parameters as in the permeability experiments were used. The results obtained showed that temperature increases of approximately 10 °C occurred following sonication. The flux changes of 3H2O across human skin between 37 °C and 42 °C were shown to be reversible. The results from the present study do not support the sonication-heating theory in which permeability changes in skin are primarily attributed to thermally-induced changes in stratum corneum lipids. It was therefore concluded that the enhancement of diclofenac permeation by sonication could not be adequately explained primarily on a thermal basis.

Thesis (Ph.D.) -- University of Western Sydney, Hawkesbury, 2001. / A thesis presented in fulfilment of the requirement for the degree of Doctor of Philosophy, College of Science, Technology and Environment, University of Western Sydney, Richmond, April 2001. Bibliography : leaves 138-148.

La stabilisation dite de Pickering repose sur l'utilisation de particules solides au lieu des émulsifiants. Leur forte adsorption aux interfaces confère à celles-ci une rigidité les protégeant de la coalescence. Ce travail se partage en quatre grandes parties. Un premier volet traite de la fabrication de ces particules et de leur caractérisation physico-chimique. Une deuxième partie traite de la formulation d'émulsions H/E selon deux procédés différents et leur caractérisation. La troisième partie avait pour but l'investigation du comportement de ces particules à l'interface H/E par diffusion de neutrons. La dernière partie traite de l'évaluation de ces émulsions pour l'application cutanée. Ce travail a pour objectif de formuler des émulsions de Pickering en utilisant des particules polymériques biodégradables. Des particules individualisées formées à partir de copolymères di-blocs du type : PCL-b-PEG et PLA-b-PEG, ont été fabriquées selon un procédé de nanoprécipitation innovant. Elles ont été caractérisées en termes de taille et de stabilité. Leur structure interne a également été investiguée par RMN et cryo-MET. Leur aptitude à stabiliser des émulsions H/E très concentrées a été démontrée. L'impact du procédé d'emulsification sur les propriétés finales a été souligné et l'adsorption de particules en forme de chapelets serrés à l'interface a été visualisée par diffusion de neutrons et microscopie électronique après cryofracture. L'absorption du rétinol dans la peau à partir de ces émulsions innovantes, a montré une accumulation accrue de cet actif dans le stratum corneum comparée à celle d'une émulsion stabilisée par des tensioactifs classiques. Cette absorption cutanée a été montrée dépendre du procédé de fabrication des émulsions. Les particules en suspension aqueuse ont aussi été testées pour l'encapsulation et la libération cutanée du rétinol. Les résultats ont montré l'influence de la constitution interne des particules (PCL ou PLA) sur l'absorption du rétinol dans la peau. L'utilisation de polymères biodégradables apporte de nouvelles perspectives dans la formulation des émulsions de Pickering à usage cosmétique ou pharmaceutique, en s'affranchissant des effets jugées hasardeux pour la santé humaine des particules inorganiques / The so-called Pickering stabilization is based on the use of solid particles instead of emulsifiers. Their strong adsorption at interfaces confers rigidity preventing them from coalescence. This work is divided into four main parts. The first part deals with the manufacture of these particles and their physicochemical characterization. A second part deals with the O/W emulsions formulation according to two different methods and their characterization. The third part is an investigation into the behavior of these particles at the O/W interface by small angle neutron scattering. The last part deals with the evaluation of these emulsions for their application to skin delivery. This work aims at the preparation of Pickering emulsions using biodegradable polymeric particles. Individual particles formed from diblock copolymers such as: PCL-b-PEG and PLA-b-PEG, were made by an innovative nanoprecipitation process. They were characterized in terms of their size and stability. Their internal structure was also investigated by NMR and cryo-TEM. Their ability to stabilize highly concentrated O/W emulsions has been demonstrated. The impact of the emulsification process on the final properties was emphasized and the adsorption of particles as tight necklaces at the interface was visualized by neutron scattering and freeze-fracture electron microscopy. The skin absorption of retinol from these innovative emulsions showed enhanced accumulation of the asset in the stratum corneum compared to conventional surfactant-stabilized emulsions. Such skin absorption of retinol was shown to depend on the manufacturing method of the emulsions. Particles in aqueous suspension were also tested for encapsulation and delivery of retinol in skin. The results showed the influence of the internal structure of the particles (PCL or PLA) on the absorption of retinol in the skin. The use of biodegradable polymers brings new perspectives in the formulation of Pickering emulsions for cosmetic or pharmaceutical use, while avoiding the effects of inorganic particles considered hazardous to human health