Desenvolvimento de nanopartículas lipídicas sólidas contendo praziquantel
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Data
2011-07-11
Autores
Souza, Ana Luiza Ribeiro de [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
O praziquantel (PZQ) é o fármaco de escolha para o tratamento da esquistossomose, sendo ativo contra todas as espécies de Schistosoma. Devido à sua baixa solubilidade em água e o risco de resistência ou tolerância do parasita a este fármaco, é importante desenvolver alternativas terapêuticas que possam aumentar sua eficácia e melhorar sua biodisponibilidade. As nanopartículas lipídicas sólidas (SLN) combinam as vantagens de diferentes carreadores coloidais tais como emulsões, lipossomas e nanopartículas poliméricas, e também evitam algumas das suas desvantagens em relação à estabilidade e dificuldade de produção em larga escala. Assim, o objetivo deste trabalho foi o desenvolvimento e caracterização de SLN contendo PZQ (SLN-PZQ) a fim de melhorar as propriedades biofarmacêuticas deste fármaco. O ácido esteárico foi selecionado como fase lipídica para o desenvolvimento das SLN devido à capacidade de solubilização do PZQ e baixo custo. As SLN foram preparadas por um método modificado de microemulsão óleoem- água sob homogeneização a alta velocidade de cisalhamento utilizando Poloxamer 188 como tensoativo. O diâmetro médio e potencial zeta das SLN-PZQ foram 505,6 nm ± 27,2 nm e -34,0 mV ± 1,1 mV, respectivamente. As nanopartículas foram observadas por microscopia eletrônica de varredura revelando a presença de partículas esféricas. Os resultados obtidos por calorimetria exploratória diferencial indicam que as SLN se apresentam no estado sólido e o fármaco está molecularmente disperso na matriz lipídica. A eficiência de encapsulação e capacidade de carga do PZQ determinadas por cromatografia líquida de alta eficiência foram 99,06 % ± 0,3 % e 17,48 % ± 0,05 %, respectivamente. A formação das SLN foi confirmada por espalhamento de raio-X a baixo ângulo revelando a presença de uma estrutura lamelar com efetiva incorporação do PZQ nas partículas
Praziquantel (PZQ) is a drug of choice for the treatment of schistosomiasis, being active against all species of Schistosoma. Due to its low water solubility and risk of parasite resistance or tolerance to this drug, it is would be useful to develop therapeutical alternatives that can increase its efficacy and improve the bioavailability. Solid lipid nanoparticles (SLN) combine the advantages of different colloidal carriers such as emulsions, liposomes, and polymeric nanoparticles, and also avoid some of their disadvantages in relation to the stability and difficulty of large scale production. Thus, the aim of this research was the development and characterization of PZQ-loaded SLN (SLN-PZQ) to improve the biopharmaceuticals properties of this drug. The stearic acid was selected as lipid phase to development of SLN due to solubilization capacity of the PZQ and low cost. The SLN were prepared by a modified oil-in-water microemulsion method under high-shear homogenization using Poloxamer 188 as surfactant. The mean particle size and zeta potential to PZQ-loaded SLN were 505.6 nm ± 27.2 nm and -34.0 mV ± 1.1 mV, respectively. The nanoparticles were observed by scanning electron microscopy (SEM) revealing the presence of spherical particles. The results obtained by differential scanning calorimetry indicate that the SLN are presented in the solid state and the drug is molecularly dispersed in the lipid matrix. The entrapment efficiency and loading capacity of PZQ determined by high performance liquid chromatography were 99.06 % ± 0.3 % and 17.48 % ± 0.05 %, respectively. The SLN formation was confirmed by small angle X-ray scattering revealing the presence of a lipid lamellar structure with effective incorporation of the PZQ into particles. The stability of PZQloaded SLN stored at room temperature and at 4 ºC was investigated concerning particle size, zeta potential and entrapment efficiency
Praziquantel (PZQ) is a drug of choice for the treatment of schistosomiasis, being active against all species of Schistosoma. Due to its low water solubility and risk of parasite resistance or tolerance to this drug, it is would be useful to develop therapeutical alternatives that can increase its efficacy and improve the bioavailability. Solid lipid nanoparticles (SLN) combine the advantages of different colloidal carriers such as emulsions, liposomes, and polymeric nanoparticles, and also avoid some of their disadvantages in relation to the stability and difficulty of large scale production. Thus, the aim of this research was the development and characterization of PZQ-loaded SLN (SLN-PZQ) to improve the biopharmaceuticals properties of this drug. The stearic acid was selected as lipid phase to development of SLN due to solubilization capacity of the PZQ and low cost. The SLN were prepared by a modified oil-in-water microemulsion method under high-shear homogenization using Poloxamer 188 as surfactant. The mean particle size and zeta potential to PZQ-loaded SLN were 505.6 nm ± 27.2 nm and -34.0 mV ± 1.1 mV, respectively. The nanoparticles were observed by scanning electron microscopy (SEM) revealing the presence of spherical particles. The results obtained by differential scanning calorimetry indicate that the SLN are presented in the solid state and the drug is molecularly dispersed in the lipid matrix. The entrapment efficiency and loading capacity of PZQ determined by high performance liquid chromatography were 99.06 % ± 0.3 % and 17.48 % ± 0.05 %, respectively. The SLN formation was confirmed by small angle X-ray scattering revealing the presence of a lipid lamellar structure with effective incorporation of the PZQ into particles. The stability of PZQloaded SLN stored at room temperature and at 4 ºC was investigated concerning particle size, zeta potential and entrapment efficiency
Descrição
Palavras-chave
Nanopartículas, Schistosoma mansoni, Esquistossomose mansonica, Praziquantel
Como citar
SOUZA, Ana Luiza Ribeiro de. Desenvolvimento de nanopartículas lipídicas sólidas contendo praziquantel. 2011. 92 f. Tese (doutorado) - Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas, 2011.