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PLGA microparticles loaded with three different fluorescent model drugs, fluorescein sodium (hydrophilic), sulforhodamine (amphoteric), and boron- dipyrromethene (BODIPY® 493/503, lipophilic), were prepared by the solvent evaporation technique. Due to varying hydrophilicity, the diameters of the microparticles ranged between 4.1 and 4.7 µm. According to fluorimetric analysis, the loading varied from 0.06 to 2.25 µg of the model drug per mg PLGA. In terms of the release profile, the fluorescein sodium-entrapped formulation exhibited thermo-responsive release kinetics. In the case of sulforhodamine- and BODIPY® 493/503-loaded particles, almost no release was observed, neither at 4°C nor 37°C during the first 50 hours. Furthermore, to estimate the bioadhesive properties of such drug delivery systems, the surface of the loaded particles was grafted with wheat germ agglutinin by applying the carbodiimide method. Cytoadhesion studies with Caco-2 monolayers revealed an up to 1.9-fold and 3.6-fold increase in the bioadhesion of the lectin-functionalized, model drug-loaded particles as compared to the albumin- and non-grafted microcarriers, respectively. All in all, the results clearly indicated that the lipophilicity of the polymer matching that of the drug favored entrapment, whereas mismatching impeded loading into the PLGA-microparticles. Even in the case of low loading, these delivery systems might be useful for the fluorescent detections and microscopic imaging of cellular interactions due to their fluorescent properties and lack of dye leakage. Moreover, lectin grafting can mediate bioadhesive properties to such particulate drug carriers which could be a promising approach to improve drug delivery. [ABSTRACT FROM AUTHOR]

Abstract: PLGA-microparticles with 4.7μm in diameter were prepared by the double emulsion technique and loaded with 1.7μg fluorescein/mg PLGA mimicking a hydrophilic API. In an effort to further elucidate the release and bioadhesive characteristics of lectin-grafted formulations in vitro, the particles were coated with wheat germ agglutinin. The microparticles exhibited thermo-responsive release since no free fluorescein was detected at 4°C or room temperature. At body temperature, however, more than 80% of the payload was released within 48h. The adhesion of lectin-grafted particles to Caco-2 monolayers, which were applied as a model for the human intestinal epithelium, exceeded that of plain ones 1.5-fold as also observed by fluorescence microscopy. Furthermore, the amount of model drug bound and taken up into the cells was 5.8-fold higher after incubation for 4h at 37°C as compared to fluorescein in solution. According to fluorescence imaging a considerable amount of the total fluorescein payload was accumulated intracellularily after incubation for 5h at 37°C. These findings not only confirm the utility of bioadhesives of the second generation for improved absorption of low molecular weight hydrophilic compounds but also indicate storage stability of such suspensions at 4°C and room temperature without any premature loss of API. [Copyright &y& Elsevier]