Dissertação de Mestrado
Desenvolvimento de micelas poliméricas carreadoras de paclitaxel radiomarcadas com tecnécio-99m para aplicação no tratamento e diagnóstico de câncer
Fecha
2015-08-03Autor
Caroline Mari Ramos Oda
Institución
Resumen
Paclitaxel (PTX) is a highly effective chemotherapeutic agent against a variety of cancers, however the use of this drug is limited due to its low aqueous solubility and high systemic toxicity. Nanocarriers based on polymeric micelles might be a promising alternative to overcome PTXs drawbacks and expand its clinical use. Micelles composed of (polyethylene glycol)2000-N-distearoyl phosphatidylethanolamine (DSPE-PEG2000) exhibit advantageous properties for application in the treatment and diagnosis of solid tumors. The functionalization of PTX-loaded micelles, with the radioisotope 99mTc complexed to diethylenetriaminepentaacetic acid (DTPA), enables the creation of an anticancer theranostic platform. In this sense, it was developed a micellar formulation made of DSPE-PEG2000:DSPE-PEG2000-99mTc-DTPA (95:5) loading PTX, and physicochemical and biological properties, required for treatment and diagnosis of cancer, were evaluated. The physicochemical properties evaluated were, critical micelle concentration (CMC), size, zeta potential and encapsulation efficiency. The micelles radiolabeled with 99mTc had their pharmacokinetic and biodistribution profiles evaluated after injection in Balb/c mice. The developed system had a CMC of 1.8 x 10-5 mol.L-1 and encapsulating efficiency of 91 ± 6%. Both, blank and micelles loading PTX, showed size and zeta potential around 10 nm and -3 mV, respectively. The DSPE-PEG2000-DTPA complex was successfully synthesized, with a mass yield of 56%. Radiolabeling yield was 94 ± 2 % , and the complex showed stable in saline and mice plasma within 8 hours, at 25 and 37 oC, respectively . In vivo studies showed a half-life of 71 minutes, with pronounced uptake in the liver and spleen and significant accumulation in the tumor region. The data indicated that the developed formulation shows suitable characteristics to increase the concentration of PTX and 99mTc in solid tumors, and consequently, improve cancer treatment and diagnosis.