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Effect of cellulose derivatives on the characteristics and nasal application of vinpocetine-loaded polymeric micelles
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Este trabalho teve como objetivo o desenvolvimento e a otimização de um sistema de administração nasal utilizando micelas poliméricas carregadas com vinpocetina. A vinpocetina, um fármaco utilizado para melhorar a função cerebral particularmente em doenças neurodegenerativas como a do Alzheimer, enfrenta desafios relacionados com a sua fraca solubilidade em água e baixa biodisponibilidade. Foi avaliada a forma como diferentes derivados de celulose - especificamente hidroxipropilmetilcelulose (HPMC), carboximetilcelulose (CMC), metilcelulose (MC) e hidroxietilcelulose (HEC) - afetam as propriedades destas micelas e a sua aplicação na administração nasal. Estas formulações foram submetidas a um processo de secagem por aspersão, formando micelas com vinpocetina, que foram objeto de vários testes.
O produto obtido através do processo de secagem por aspersão foi caracterizado, determinando o tamanho das partículas e o teor do fármaco. As micelas foram também estudadas no estado líquido e, neste caso, foram determinados o seu tamanho, a distribuição, o potencial zeta, a eficiência de encapsulação e a solubilidade termodinâmica. Foram ainda efetuados estudos de aplicabilidade nasal in vitro, com estudos de libertação e permeação do fármaco.
A caraterização das partículas mostrou que as formulações com HEC e HPMC apresentavam as distribuições de tamanho de partículas mais uniformes. A eficiência de encapsulamento foi mais elevada com HEC a 0.5%, demonstrando um encapsulamento quase completo do fármaco. Já os estudos de libertação do fármaco in vitro indicaram que todas as formulações apresentaram uma libertação rápida nos primeiros 15-20 minutos, crucial para a administração nasal. Os testes de permeabilidade ao fármaco demonstraram ainda que concentrações mais baixas de HEC e HPMC proporcionaram uma permeabilidade superior, sugerindo uma janela de concentração eficaz entre 0.5% e 1.5%.
Estes resultados realçam o potencial dos derivados de celulose na otimização de micelas carregadas com vinpocetina para administração nasal. O estudo sugere que tais formulações podem ser desenvolvidas para melhorar a eficácia dos tratamentos em doenças neurodegenerativas.
This study aimed the development and optimization of a nasal drug delivery system using vinpocetine-loaded polymeric micelles, improving bioavailability and solubility. Vinpocetine, a drug utilized to enhance brain function and cerebral blood circulation, particularly for conditions like neurodegenerative diseases such as Alzheimer’s Disease, dementia, faces challenges related to its poor water solubility and low bioavailability. The research investigates how different cellulose derivatives - specifically Hydroxypropyl-methylcellulose (HPMC), Carboxymethyl-cellulose (CMC), Methylcellulose (MC), and Hydroxyethyl-cellulose (HEC) - affect the properties of these polymeric micelles and their application in nasal drug delivery. These formulations were nano spray-dried, forming vinpocetine-loaded polymeric micelles, which were the subject of various tests. The solid-state formulations were characterized, by determining the particle size and the drug content. The liquid state formulations were also analyzed and, in this case, the micelle size, micelle size distribution, zeta potential, encapsulation efficiency and thermodynamic solubility of each formulation were determined. In vitro nasal applicability studies were also done, with drug release and drug permeation studies. Solid-state characterization, including particle size determination via laser diffraction, showed that formulations with HEC and HPMC exhibited the most uniform particle size distributions. Encapsulation efficiency was highest with HEC at 0.5% w/v, demonstrating almost complete drug encapsulation. In vitro drug release studies indicated that all formulations showed rapid release within the first 15-20 minutes, crucial for nasal administration. Drug permeability tests further demonstrated that lower concentrations of HEC and HPMC provided optimal permeability, suggesting an effective concentration window between 0.5% and 1.5%. These findings highlight the potential of cellulose derivatives in optimizing vinpocetine-loaded micelles for nasal delivery, supporting their viability for enhancing brain-targeted drug therapies. It was also crucial to determine the effect of these polymers on the nasal application, as they are commonly applied viscosity enhancers for liquid nasal dosage forms. The study suggests that such formulations could be further developed to improve the efficacy of treatments for neurodegenerative diseases.
This study aimed the development and optimization of a nasal drug delivery system using vinpocetine-loaded polymeric micelles, improving bioavailability and solubility. Vinpocetine, a drug utilized to enhance brain function and cerebral blood circulation, particularly for conditions like neurodegenerative diseases such as Alzheimer’s Disease, dementia, faces challenges related to its poor water solubility and low bioavailability. The research investigates how different cellulose derivatives - specifically Hydroxypropyl-methylcellulose (HPMC), Carboxymethyl-cellulose (CMC), Methylcellulose (MC), and Hydroxyethyl-cellulose (HEC) - affect the properties of these polymeric micelles and their application in nasal drug delivery. These formulations were nano spray-dried, forming vinpocetine-loaded polymeric micelles, which were the subject of various tests. The solid-state formulations were characterized, by determining the particle size and the drug content. The liquid state formulations were also analyzed and, in this case, the micelle size, micelle size distribution, zeta potential, encapsulation efficiency and thermodynamic solubility of each formulation were determined. In vitro nasal applicability studies were also done, with drug release and drug permeation studies. Solid-state characterization, including particle size determination via laser diffraction, showed that formulations with HEC and HPMC exhibited the most uniform particle size distributions. Encapsulation efficiency was highest with HEC at 0.5% w/v, demonstrating almost complete drug encapsulation. In vitro drug release studies indicated that all formulations showed rapid release within the first 15-20 minutes, crucial for nasal administration. Drug permeability tests further demonstrated that lower concentrations of HEC and HPMC provided optimal permeability, suggesting an effective concentration window between 0.5% and 1.5%. These findings highlight the potential of cellulose derivatives in optimizing vinpocetine-loaded micelles for nasal delivery, supporting their viability for enhancing brain-targeted drug therapies. It was also crucial to determine the effect of these polymers on the nasal application, as they are commonly applied viscosity enhancers for liquid nasal dosage forms. The study suggests that such formulations could be further developed to improve the efficacy of treatments for neurodegenerative diseases.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2024, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Vinpocetine Nasal administration Polymeric micelles Cellulose derivatives Spray drying Mestrado Integrado - 2024