Macrophages possess an innate ability to scavenge heterogenous objects from the systemic circulation and to regulate inflammatory diseases in various organs via cytokine production. That makes them attractive targets for nanomedicine-based therapeutic approaches to inflammatory diseases. In the present study, we have prepared several different poly(lactic-co-glycolic acid) (PLGA) polymer nanospheres for macrophage-targeted drug delivery using both nanoprecipitation and emulsification solvent evaporation methods. Two experimental linear PLGA polymers with relatively low molar weight, one experimental branched PLGA with unique star-like molecular architecture, and a commercially available PLGA, were used for nanosphere formulation and compared to their macrophage uptake capacity. The nanosphere formulations labelled with loaded fluorescent dye Rhodamine B were further tested in mouse bone marrow-derived macrophages and in hepatocyte cell lines AML-12, HepG2. We found that nanospheres larger than 100 nm prepared using nanoprecipitation significantly enhanced distribution of fluorescent dye selectively into macrophages. No effects of nanospheres on cellular viability were observed. Additionally, no significant proinflammatory effect after macrophage exposure to nanospheres was detected as assessed by a determination of proinflammatory cytokines Il-1β and Tnfα mRNA. All experimental PLGA nanoformulations surpassed the nanospheres obtained with the commercially available polymer taken as a control in their capacity as macrophage-specific carriers.

Centre National de la Recherche Scientifique 3 rue Michel Ange 75016 Paris France

Department of Molecular Pathology and Biology Faculty of Military Health Science University of Defence in Brno Trebesska 1575 500 01 Hradec Kralove Czech Republic

Department of Pharmaceutical Technology Faculty of Pharmacy in Hradec Kralove Charles University Akademika Heyrovskeho 1203 500 05 Hradec Kralove Czech Republic

Department of Pharmacology and Toxicology Faculty of Pharmacy in Hradec Kralove Charles University Akademika Heyrovskeho 1203 500 05 Hradec Kralove Czech Republic

Faculty of Chemical Technology University of Chemistry and Technology Technicka 5 166 28 Prague Czech Republic

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