Abstract
The use of drug delivery system based on polymeric nanoparticles (PNP) has been investigated due to its capacity to carrier hydrophobic drugs across natural barriers and to access new sites in the human body to release drugs at different tissues or cells. In the present work, polyethylene glycol monomethyl ether – co – polycaprolactone copolymer (mPEG-co-PCL) was synthesized by ring opening polymerization of the ε-caprolactone in the presence of polyethylene glycol monomethyl ether (mPEG) as a macroinitiator and tin(II) 2-ethylhexanoate (Sn (Oct)2), as a catalyst. On this step, three syntheses were realized to increase the polycaprolactone (PCL) hydrophobic segment of the copolymer. PNP of mPEG-co-PCL were obtained by emulsion – solvent evaporation method, which the surfactant concentration (Tween80®), cosurfactant (dodecane) and water/oil ratio were studied to control the size of nanoparticles. The PNP ability to loading and releasing drugs was evaluated with methotrexate (MTX), a drug commonly used for cancer treatment. The copolymers were synthesized with different chain length, increasing PCL hydrophobic segment, resulting in molecular weight between 2,000 to 13,000 g mol−1. The lowest hydrodynamic diameter (79.5 nm) of PNP was obtained with a solution of 1 × 10-4 mol L−1 Tween80® solution and 500 u L of dodecane. The water/oil ratio showed insignificant influence on hydrodynamic diameter, according to factorial design results. The copolymers showed a loading efficiency of MTX higher than 80.0%. The MTX releases from mPEG-co-PCL platform had occurred by anomalous transport mechanism in the first hours. After 16 h the release rate of MTX decrease drastically and its behavior was governed by PCL degradation process. As PCL ratio is increased on copolymer, the drug release decrease, suggesting an interaction of MTX with PNP hydrophobic segment. Thus, the MTX release could be controlled by copolymer chain length through hydrophilic and hydrophobic segment composition ratio, being a good candidate for hydrophobic drug delivery systems.
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