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Development of hybrid lipidic-polymeric nanoparticles with hyaluronic acid encapsulating Dimethylfumarate and Rutin by modified nanoprecipitation
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Abstract(s)
Contexto: O fumarato de dimetilo, fármaco utilizado na esclerose múltipla, e a rutina, um bioflavonóide, são ambos agentes anti-neuroinflamatórios relacionados a doenças degenerativas, apresentando, porém, uma fraca solubilidade e uma limitada biodisponibilidade. Para contornar estas questões, a nanotecnologia tem feito avanços notáveis na melhoria de tais problemas. Assim, nanopartículas híbridas lipídico-poliméricas foram sintetizadas, aproveitando o benefício de ambos os componentes para melhorar o efeito terapêutico e facilitar a administração por via intranasal, uma vez que existe uma ligação anatómica entre a cavidade nasal e o sistema nervoso central. Objetivo: O propósito deste estudo é avaliar como diferentes quantidades de diversos excipientes na formulação afetam a caracterização físico-química, bem como determinar a técnica de preparação mais eficaz. Métodos: Nanoprecipitação modificada, em que o componente orgânico consiste em fosfatidilcolina ou num lípido peguilado dissolvido em etanol, enquanto o componente polimérico é representado pelo ácido hialurónico dissolvido em água. As duas primeiras formulações foram produzidas apenas com o recurso ao sonicador, enquanto as restantes formulações foram produzidas com o método da bomba de seringa de perfusão, envolvendo a adição gradual de gota a gota de óleo na água. Ambas as abordagens foram seguidas de evaporação do solvente e caraterização físico-química, juntamente com a eficácia do aprisionamento das substâncias ativas. Resultados: A nanoprecipitação modificada feita com o sonicador produziu nanopartículas maiores do que as feitas com o auxílio da bomba de seringa de infusão e a distribuição de tamanho foi heterogénea na maior parte das formulações. Em geral, a percentagem de poloxâmero, colesterol, palmitoiletanolamida, a escolha do componente lipídico e a ausência de ácido hialurónico afetam o tamanho das partículas das formulações. A formulação de 8 poderá ser a mais adequada para a administração intranasal de fumarato de dimetilo, enquanto as formulações 13 ou 14 poderiam transportar rutina pela mesma via.
Background: Dimethylfumarate, a medication employed in multiple sclerosis, and Rutin, a bioflavonoid, are both recognized as anti-neuroinflammatory agents linked to neurodegenerative diseases. Nevertheless, they present poor solubility and a limited bioavailability. To tackle these challenges, nanotechnology has made a remarkable advancement in ameliorating such issues. Therefore, hybrid lipidic-polimeric nanoparticles have been synthesized, taking leverage of both components to enhance the therapeutic effect and facilitate the intranasal route as there is an anatomical connection between the nasal cavity and the central nervous system. Purpose: The aim of this study is to evaluate how different quantities of several excipients on nanoparticles impacts the physicochemical characterization of the formulation as well as to determine the most effective preparation technique. Methods: Modified nanoprecipitation, wherein the organic component consisted of either phosphatidylcholine or a PEGylated-lipid dissolved in ethanol, while the polymeric component is represented by hyaluronic acid dissolved in water. The first two formulations were produced only with the resource of the vortex while the remaining formulations were produced with the syringe pump method, involving the gradual dropwise addition of oil into the water. Both approaches were followed by solvent evaporation and physicochemical characterization along with entrapment efficacy. Results: The modified nanoprecipitation performed with the sonicator resulted in larger nanoparticles compared to those produced using the syringe pump. In general, the percentage of poloxamer, cholesterol, palmitoylethanolamide, the choice of the lipid component, and the absence of hyaluronic acid affect the particle size in the formulations. Formulation 8 may be the most suitable for intranasal delivery of dimethyl fumarate, while formulations 13 or 14 could transport rutin via the same route.
Background: Dimethylfumarate, a medication employed in multiple sclerosis, and Rutin, a bioflavonoid, are both recognized as anti-neuroinflammatory agents linked to neurodegenerative diseases. Nevertheless, they present poor solubility and a limited bioavailability. To tackle these challenges, nanotechnology has made a remarkable advancement in ameliorating such issues. Therefore, hybrid lipidic-polimeric nanoparticles have been synthesized, taking leverage of both components to enhance the therapeutic effect and facilitate the intranasal route as there is an anatomical connection between the nasal cavity and the central nervous system. Purpose: The aim of this study is to evaluate how different quantities of several excipients on nanoparticles impacts the physicochemical characterization of the formulation as well as to determine the most effective preparation technique. Methods: Modified nanoprecipitation, wherein the organic component consisted of either phosphatidylcholine or a PEGylated-lipid dissolved in ethanol, while the polymeric component is represented by hyaluronic acid dissolved in water. The first two formulations were produced only with the resource of the vortex while the remaining formulations were produced with the syringe pump method, involving the gradual dropwise addition of oil into the water. Both approaches were followed by solvent evaporation and physicochemical characterization along with entrapment efficacy. Results: The modified nanoprecipitation performed with the sonicator resulted in larger nanoparticles compared to those produced using the syringe pump. In general, the percentage of poloxamer, cholesterol, palmitoylethanolamide, the choice of the lipid component, and the absence of hyaluronic acid affect the particle size in the formulations. Formulation 8 may be the most suitable for intranasal delivery of dimethyl fumarate, while formulations 13 or 14 could transport rutin via the same route.
Description
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2023, Universidade de Lisboa, Faculdade de Farmácia.
Keywords
Dimethyl fumarate; Rutin; Multiple Sclerosis; Nanoparticles; Multiple Sclerosis; Intranasal route; Rutin Multiple sclerosis Nanoparticles Intranasal route Mestrado Integrado - 2023