PLGA-based microparticles as a new system for the toxicological studies of phthalates

Purpose: Microparticles have been extensively employed for the encapsulation of drugs in order to achieve a modulated release profile or a specific therapeutic action [1, 2]. However, very few studies have reported the use of microparticles as nanocarriers for poorly water soluble substances associated with health concerns and toxicological environmental risks [3]. The aim of the present work was the preparation of biodegradable polymeric microparticles for the encapsulation of phthalates in order to assess their toxicological profile on cell lines and animal models. Methods: PLGA microparticles were prepared through the emulsification method. First, the plasticizing effect of dibutyl phthalate (DBP) on the glass transition temperature of PLGA was evaluated. Then, DBP was encapsulated inside the microparticles and the drug content (%) was determined. Particle size distribution was analysed by image analysis and a single particle optical sizing (SPOS) system. Finally, the release study in 1.5% of SDS as medium was performed. Results: The prepared microparticles showed a spherical shape, a low mean particle size (approximately 3 µm) and a narrow particle size distribution. The loading with DBP did not markedly affect the properties of the microparticles in terms of size and shape. Microparticles were recovered with a good yield (65-69%) despite the plasticizing effect of phthalate on PLGA. Release study of DBP in a 1.5% SDS solution as medium showed the typical release profiles of biodegradable microparticles in which an initial high-rate release phase (burst effect) is followed by a sustained release over several days. Conclusions: PLGA based microparticles are promising nanocarriers suitable for the encapsulation and the delivery of phthalates both in vitro and in vivo. The optimized system will be employed to perform toxicological studies on selective cell lines and animal models.