Accessing lipophilicity of drugs with biomimetic models: A comparative study using liposomes and micelles

Lipophilicity is a physicochemical property of crucial importance in drug discovery and drug design. Biomimetic models, such as liposomes and micelles, constitute a valuable tool for the assessment of lipophilicity through the determination of partition coefficients (log Kp). However, the lack of standardization hampers the judgment about which model or method has the best and broadest passive drug permeation predictive capacity. This work provides a comparative analysis between the methodologies based on biomimetic models to determine the partition coefficient (log Kp). For that purpose, a set of reference substances preconized by the Organization for Economic Cooperation and Development (OECD) guidelines was used. The biomimetic models employed were liposomes and micelles composed by 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) and hexadecylphosphocholine (HePC), respectively. Both lipids were used as representative phospholipids of natural membranes. The partition coefficients between biomimetic models and aqueous phases were determined by derivative spectroscopy at physiological conditions (37 °C and pH 7.4). The partition coefficients obtained using biomimetic models are quite different and more reliable than the ones obtained using an octanol/water system. Comparing the performance of the two biomimetic models, micelles revealed to be suitable only for substances with high molar absorption coefficient and log Kp > 3, but in general liposomes are the best model for accessing lipophilicity of drugs. Furthermore, a comparison between experimental data and the partition coefficients determined by the computational method COSMOmic is also provided and discussed. As a final summarizing result, a decision tree is provided in order to guide the selection of a tool for assessing the lipophilicity of drugs. © 2018 ElsevierThis work was supported by European Union (FEDER funds POCI/01/0145/FEDER/007265 ) and National Funds (FCT/MEC, Fundação para a Ciência e Tecnologia and Ministério da Educação e Ciência) under the Partnership Agreement PT2020 UID/QUI/50006/2013 ; through the FCT PhD Programmes and by Programa Operacional Capital Humano (POCH), specifically by the BiotechHealth Programme (Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences), reference PD/00016/2012; through the FCT and POCH for the PhD grants (SFRH/BD/98105/2013 and PD/BD/105957/2014, respectively) and for the Investigator grant (IF/00293/2015); and through the financial support of the German Academic Exchange Service (DAAD). The authors would also like to thank Sara Cravo and Gisela Adriano for the technical support. Appendix

A comunicação alternativa como procedimento de desenvolvimento de habilidades comunicativas Augmentative and alternative communication as a procedure for developing communication skills

O estudo teve como objetivo planejar, aplicar e avaliar os efeitos de um programa de intervenção sobre Comunicação Alternativa para o desenvolvimento de habilidades comunicativas de uma adolescente com deficiência intelectual. Participaram da pesquisa uma menina de 14 anos, com diagnóstico de deficiência intelectual e déficits na comunicação verbal, a mãe e a educadora da adolescente. Para verificar os efeitos da intervenção, foi utilizado o delineamento de sujeito único, do modelo AB. Nos resultados da avaliação pragmática, por meio do teste ABFW, ao comparamos o desempenho da participante antes e após a intervenção, verificou-se um aumento dos atos comunicativos e melhora significativa do conteúdo dialógico. Na Avaliação de Linguagem Receptiva e Expressiva, a participante obteve êxito em todos os itens da seção não verbal (pré e pós teste). Na seção verbal, após o processo de intervenção, a participante adquiriu a habilidade de imitar sons e iniciar diálogos. Na análise dos questionários aplicados aos pais e professora da adolescente, foi possível perceber alguns pontos de divergência quanto a habilidade em comunicar desejos e sentimentos e na execução de ordens dadas. Com o início do processo de intervenção, e com a introdução do Sistema de Comunicação Alternativa - PECS verificou-se que a participante passou a utilizar as figuras pictográficas como recurso comunicativo durante situações da vida diária. Embora a participante apresentasse comunicação verbal antes do início do processo de intervenção, essa comunicação não era eficiente durante as interações. Assim, a participante utilizou o Sistema de Comunicação como alternativa para aprimorar suas habilidades linguísticas, além de complementar sua comunicação oral.<br>The study was designed to plan, implement and evaluate the effects of an Alternative Communication intervention program for developing the communication skills of a teenager with intellectual disabilities. The participants in the study were a 14 year old girl, diagnosed with intellectual disabilities and deficits in verbal communication, as well as her mother and her teacher. To verify the effects of the intervention, a single subject AB model design was used. When the participant's performance was compared before and after intervention, the results of the pragmatic evaluation through ABFW test showed an increase of communication performances and significant improvement of content dialogue. In Evaluation of Receptive and Expressive Language, the participant was successful on all items of the non-verbal section (pre and post test). In the verbal section, after the intervention process, the participant had acquired the ability to imitate sounds and initiate dialogue. When analyzing parents and teacher questionnaires, some points of disagreement in terms of the ability to communicate desires and feelings as well as carrying out given orders were revealed. After starting the intervention process, which introduced the PECS Alternative Communication System, it was found that the participant began to use pictograms as communication resources for daily life situations. Although the participant presented oral communication before the intervention process, her communication was not efficient during interactions. The intervention enabled the participant to use the communication system as an alternative, improving her language skills, and supplementing her oral communication