Micropartículas de ácido poli lático-co-glicólico obtidas por Spray Drying para liberação prolongada intra-ocular de fármacos
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Data
2008-04-11
Autores
Silva Júnior, Arnóbio Antonio da [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
O presente trabalho teve o objetivo obter mediante a técnica de “spray drying”, dois sistemas microparticulados a base de ácido poli lático-co-glicólico (PLGA) capazes de proporcionar níveis terapêuticos do fármaco administrado nos tecidos intraoculares. O primeiro sistema foi desenvolvido para o ciprofloxacino (CP), que é uma quinolona de segunda geração, para o uso em profilaxia e tratamento de endoftalmites. Enquanto, o segundo sistema foi para triancinolona (Tr), que é um antiinflamatório esteroidal, para uso no tratamento de diversas afecções do seguimento posterior do olho e doenças vitreoretinais. Como técnica de esterilização foi escolhida a irradiação gama, e para determinar o seu efeito, as micropartículas foram caracterizadas antes e depois da exposição a diferentes cargas de radiação (5,10,15 e 25kGy) quanto à morfologia, tamanho médio de partícula e a distribuição do tamanho de partículas usando a microscopia eletrônica de varredura. As interações fármaco-polímero e a microestrutura foram estudadas através da espectroscopia de absorção na região do infravermelho (IV), Calorimetria exploratória diferencial (DSC) e Análise termogravimétrica e Termogravimetria derivada (ATG/DTG), e Difratometria de raios X. O teor de fármaco foi determinado por cromatografia líquida de alta eficiência (CLAE) e foi investigado o perfil de liberação in vitro do fármaco a partir das micropartículas de PLGA. Após a esterilização das micropartículas utilizando a carga de 25kGy de radiação gama, foi realizado o estudo in vivo em coelho albino como modelo animal, para o estudo de biodisponibilidade e determinação dos parâmetros farmacocinéticos dos sistemas administrados. A dose de 1mg/0,1mL de triancinolona em micropartículas foi administrada por via intravitreal e como controle foi utilizado a mesma dose do fármaco em suspensão.
The present work has the aim to obtain two spray dried poly lactide-co-glycolide microparticle systems able to supply therapeutic level by prolonged time of the drugs in the intraocular tissues. The first was developed for ciprofloxacin that is a quinolone derivative aiming its use in the prophylaxis and endophthalmitis treatment, while the second system was for triamcinolone that is a steroidal anti-inflammatory for treatment of several ocular diseases of posterior segment of eye and vitreoretinal diseases. The gamma irradiation was chosen as terminal sterilization procedure, and with aim to determine its effect, the drug-loaded PLGA microparticles were characterized after the radiation exposure (0, 5,10, 15 and 25 kGy). The morphology and particle size were investigated by scanning electronic microscopy (SEM). The drug-polymer interactions and the microstructure of the particles were accessed by infrared spectroscopy, differential scanning calorimetry (DSC); thermogravimetry and derivative thermogravimetry (TG/DTG) and X-ray diffraction analysis. The drug content was determined by high performance liquid chromatography (HPLC) and the in vitro drug release profile from PLGA microparticles was determined. After the gamma irradiation sterilization using the dose of 25kGy, the in vivo study was performed using healthy New Zeeland rabbit as animal model for bioavailability study and to determine the pharmacokinetic parameters. A dosage of 1mg.mL-1 of Triamcinolone into PLGA microparticles was administered by intravitreal route. As control, the same dosage of non-encapsulated drug was administered in aqueous suspension. In the ciprofloxacin case, the dosage of 2mg.mL-1 into PLGA microparticles was administered by sub-tenon’s rout. As control, the same dosage of drug was administered in aqueous solution. The efficacy of CP-loaded PLGA microparticles was investigated too, using the ciprofloxacin 0.3% eye drops as control.
The present work has the aim to obtain two spray dried poly lactide-co-glycolide microparticle systems able to supply therapeutic level by prolonged time of the drugs in the intraocular tissues. The first was developed for ciprofloxacin that is a quinolone derivative aiming its use in the prophylaxis and endophthalmitis treatment, while the second system was for triamcinolone that is a steroidal anti-inflammatory for treatment of several ocular diseases of posterior segment of eye and vitreoretinal diseases. The gamma irradiation was chosen as terminal sterilization procedure, and with aim to determine its effect, the drug-loaded PLGA microparticles were characterized after the radiation exposure (0, 5,10, 15 and 25 kGy). The morphology and particle size were investigated by scanning electronic microscopy (SEM). The drug-polymer interactions and the microstructure of the particles were accessed by infrared spectroscopy, differential scanning calorimetry (DSC); thermogravimetry and derivative thermogravimetry (TG/DTG) and X-ray diffraction analysis. The drug content was determined by high performance liquid chromatography (HPLC) and the in vitro drug release profile from PLGA microparticles was determined. After the gamma irradiation sterilization using the dose of 25kGy, the in vivo study was performed using healthy New Zeeland rabbit as animal model for bioavailability study and to determine the pharmacokinetic parameters. A dosage of 1mg.mL-1 of Triamcinolone into PLGA microparticles was administered by intravitreal route. As control, the same dosage of non-encapsulated drug was administered in aqueous suspension. In the ciprofloxacin case, the dosage of 2mg.mL-1 into PLGA microparticles was administered by sub-tenon’s rout. As control, the same dosage of drug was administered in aqueous solution. The efficacy of CP-loaded PLGA microparticles was investigated too, using the ciprofloxacin 0.3% eye drops as control.
Descrição
Palavras-chave
Liberção intra-ocular de fármacos, Micropartículas biodegradáveis, Radiação gama, Spary drying
Como citar
SILVA JÚNIOR, Arnóbio Antonio da. Micropartículas de ácido poli lático-co-glicólico obtidas por Spray Drying para liberação prolongada intra-ocular de fármacos. 2008. 177 f. Tese (Doutorado) - Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas, 2008.