Abstract
This study explores the hypothesis that the colloidal properties of nanocarriers can modulate the interaction of hydrophilic and anionic chemotherapy agents with biological surfaces, especially tumoral cells. Different compositions were tested for preparing poloxamer-stabilized poly (lactic-co-glycolic acid) (PLGA) nanoparticles. Surface covering with the cationic hyperbranched polyethyleneimine (PEI) is tailored to improve methotrexate (MTX) efficacy against cancer cells. Two types of poloxamer (188 and 407) were tested as surfactants against different concentrations of PLGA in a nanoprecipitation method. Small and uniformly sized PLGA nanoparticles (90 to 110 nm) were produced with a neutral/slightly negative charge and low-drug loading efficiency. These limitations were resolved and improved by varying the PEI:PLGA ratio. The cationic-functionalized MTX-loaded nanoparticles showed a diameter of approximately 170 nm and a drug loading efficiency higher than 80%. The slow drug release profile was best fitted using the first order and the Peppas–Sahlin non-linear models. Fluorescence microscopy experiments reinforce the notion that drug uptake is improved using the functionalized nanoparticles. Cell viability assays reveal the biocompatibility of the drug-free cationic-functionalized nanoparticles and the increased efficacy of MTX-loaded cationic nanoparticles.
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