The resonant behavior of airborne standing-wave acoustic levitators based on arrays of ultrasonic transducers.

Recently airborne standing-wave acoustic levitation has seen great advances, and its applicability has been broadened due to the development of cavities constructed with arrays of compact ultrasonic sources. Yet, the numerical methods employed to study and predict the pressure distributions inside these cavities do not consider the effect of multiple reflections on the boundaries, hiding their resonant effects. This work presents an analytical, numerical, and experimental study of the effect of multiple reflections inside ultrasonic cavities based on arrays of transducers exhibiting their influence on the pressure amplitudes of focused standing waves. Our numerical results come from a modified version of the Matrix Method to numerically compute the multiple wave reflections of cavities constructed by two opposite arrays of multiple compact sources as boundaries. The correlation between numerical and experimental results reveals that intra-cavity reflections are relevant in focused axisymmetric cavities based on two arrays of multiple ultrasonic sources having a considerable impact on the amplitude of the standing waves and consequently, on the acoustic levitation performance. Thus, intra-cavity reflections must be considered for optimal cavity designs.

Innovative pharmaceutical strategies for niclosamide repositioning / Estratégias farmacêuticas inovadoras para o reposicionamento da niclosamida

The antiparasitic niclosamide has shown promising anticancer activity in preclinical studies against several types of cancer, such as colorectal and prostate. Thus, the objective of this work was to develop innovative formulations for the repositioning of niclosamide as an anticancer agent. In chapter I, a critical review of the literature on the physicochemical properties of the drug was carried out, in addition the results of clinical studies against colorectal and prostate cancer. Besides, a review was carried out on studies that developed formulations containing this drug, as well as hypotheses to improve the biopharmaceutical performance of this molecule. In chapter II, the development of solid amorphous dispersion containing niclosamide was carried out. Drug/polymer solutions were acoustic levitated and characterized by synchrotron X-ray light. This set allowed fast, high quality measurements, as well as the identification of niclosamide recrystallization. Plasdone® and Soluplus® demonstrated better properties to form amorphous dispersions, with the latter showing superior solubility enhancement. The study showed that the developed formulation increased the apparent saturation solubility of niclosamide in water by two times. In chapter III the objective was the development, physicochemical characterization and in vitro anticancer activity of a niclosamide nanoemulsion, having HCT-116 cells as a cellular model. Preliminary results indicated Capmul® MCM C8 as the best liquid lipid for the system, but the first nanoemulsions containing this lipid were not stable to justify its usage. On the other hand, Miglyol® 812 indicated to be a suitable liquid lipid for the system. The niclosamide nanoemulsion (~200 nm) with Miglyol® 812 and poloxamer 188 was stable for 56 days, with a monomodal particle size distribution. Cell viability assay against HCT-116 cells demonstrated that niclosamide cytotoxicity is time and concentration dependent. Results herein obtained encourage further research to understand and optimize niclosamide performance as an anticancer drug substance

O antiparasitário niclosamida tem apresentado promissora atividade anticâncer em estudos pré- clínicos contra diversos tipos de câncer, como coloretal e próstata. Assim, o objetivo deste trabalho foi desenvolver formulações inovadoras para o reposicionamento da niclosamida como agente anticâncer. No capítulo I foi realizada revisão crítica da literatura sobre as propriedades físico-químicas do fármaco, além de resultados de estudos clínicos da niclosamida contra câncer de coloretal e de próstata. Além disso, foi feita revisão sobre estudos que desenvolveram formulações contendo esse fármaco, bem como hipóteses para melhorar o desempenho biofarmacêutico dessa molécula. No capítulo II foi realizado o desenvolvimento de dispersão solida amorfa contendo niclosamida. Soluções de fármaco/polímero foram levitadas em levitador acústico e caracterizadas por raios-X de luz síncrotron. Este conjunto permitiu medições rápidas e de alta qualidade, bem como identificação de recristalização da niclosamida. Plasdone® e Soluplus® demonstraram melhores propriedades para formar as dispersões amorfas, com o último apresentando aumento de solubilidade superior. O estudo mostrou que a formulação desenvolvida aumentou em duas vezes a solubilidade aparente de saturação da niclosamida em água. No capítulo III o objetivo foi o desenvolvimento, a caracterização físicoquímica e atividade anticâncer in vitro de uma nanoemulsão de niclosamida, tendo células HCT-116 como modelo celular. Resultados preliminares indicaram o Capmul® MCM C8 como o melhor lipídio líquido para o sistema, mas as primeiras nanoemulsões contendo este lipídio não foram estáveis para justificar seu uso. Por outro lado, Miglyol® 812 indicou ser um lipídio líquido adequado para o sistema. A nanoemulsão de niclosamida (~200 nm) com Miglyol® 812 e poloxâmero 188 foi estável por 56 dias, com distribuição monomodal do tamanho de partícula. O ensaio de viabilidade celular contra células HCT-116 demonstrou que a citoxicidade da niclosamida é dependente do tempo e da concentração. Os resultados aqui obtidos encorajam mais pesquisas para entender e otimizar o desempenho da niclosamida como uma substância anticancerígena

Acoustic levitation and high-resolution synchrotron X-ray powder diffraction: A fast screening approach of niclosamide amorphous solid dispersions.

The levitation of samples in an acoustic field has been of interest in the preparation and study of amorphous solid dispersions (ASD). Here, niclosamide-polymer solutions were levitated in a multi-emitter single-axis acoustic levitator and analyzed for 10 min at a High-resolution synchrotron X-ray powder diffraction beamline. This assembly enabled high-quality and fast time-resolved measurements with microliter sample size and measurement of solvent evaporation and recrystallization of niclosamide (NCL). Polymers HPMCP-55S, HPMCP-50, HPMCP-55, Klucel®, and poloxamers were not able to form amorphous dispersions with NCL. Plasdone® and Soluplus® demonstrated excellent properties to form NCL amorphous dispersions, with the last showing superior solubility enhancement. Furthermore, this fast levitation polymer screening showed good agreement with results obtained by conventional solvent evaporation screening evaluated for five days in a stability study, carried out at 40 °C/75% RH. The study showed that acoustic levitation and high-resolution synchrotron combination opens up a new horizon with great potential for accelerating ASD formulation screening and analysis.