In vitro and in vivo evaluation of poly(methylidene malonate 2.1.2) microparticles behavior for oral administration

The goal of this paper was to investigate the fate of novel poly(methylidene malonate 2.1.2) microparticles with different surface properties, i.e. prepared with or without polyvinylalcohol (PVA), after oral administration, using in vitro cell culture and an in vivo mice model. Incubation of particles with Caco-2 cells induced no cytotoxicity except for the microparticles prepared without PVA at high concentrations. At subtoxic concentrations, microparticles were highly associated to cells, independently of particles concentrations, particles surface properties (with or without PVA) or incubation time. Confocal microscopy analysis revealed that adsorption was the main phenomenon leading to the association of particles to cells. However, association was greater at 37 degrees C than at 4 degrees C, suggesting that an active process, such as endocytosis, could also occur. In vivo, radiolabeled particles were mainly found in luminal content and also adsorbed onto the epithelium. After 24 hours, more than 15% of PVA-free microparticles were still present in the gastrointestinal tract, compared to 5% for particles prepared with PVA. However, histological evaluation revealed low uptake of particles by Peyer's patches. As a conclusion, this study provided a good correlation between in vitro and in vivo evaluation. These particles could be useful for oral sustained release and delivery of drugs to intestinal and colon epithelium.