title: Folic acid-functionalized human serum albumin nanocapsules for targeted drug delivery to chronically activated macrophages.
abstract: Activated synovial macrophages play a key role in Rheumatoid Arthritis (RA). Recent studies have shown that folate receptor beta (FRβ) is specifically expressed by activated macrophages. Therefore a folate-based nanodevice would provide the possibility of delivering therapeutic agents to activated macrophages without affecting normal cells and tissues. This study shows for the first time the sonochemical preparation of HSA nanocapsules avoiding toxic cross linking chemicals and emulsifiers used in other methods. Production of HSA nanocapsules was optimized leading to a diameter of 443.5 ± 9.0 nm and a narrow size distribution indicated by a polydispersity index (PDI) of 0.066 ± 0.080. Nanocapsules were surface modified with folic acid (FA) and the FA content was determined to be 0.38 and 6.42 molecules FA per molecule HSA, depending on the surplus of FA employed. Dynamic light scattering was used to determine size, PDI and zetapotential of the produced nanocapsules before and after surface modification. FA distribution on the surface of HSA nanocapsules was localized three-dimensionally after fluorescence labeling using confocal laser scanning microscopy (CLSM). Furthermore, specific binding and internalization of HSA nanocapsules by FRβ-positive and FRβ-negative macrophages, obtained from human peripheral blood mononuclear cells, was demonstrated by flow cytometry. FRβ-expressing macrophages showed an increased binding for FA-modified capsules compared with those without FA.
authors.affiliation: Graz University of Technology, Institute of Environmental Biotechnology, Petersgasse 12, 8010 Graz, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rollett
authors.forename: Tamara
authors.initials: T
authors.lastname: Reiter
authors.forename: Patricia
authors.initials: P
authors.lastname: Nogueira
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cardinale
authors.forename: Ana
authors.initials: A
authors.lastname: Loureiro
authors.forename: Andreia
authors.initials: A
authors.lastname: Gomes
authors.forename: Artur
authors.initials: A
authors.lastname: Cavaco-Paulo
authors.forename: Alexandra
authors.initials: A
authors.lastname: Moreira
authors.forename: Alexandre M
authors.initials: AM
authors.lastname: Carmo
authors.forename: Georg M
authors.initials: GM
authors.lastname: Guebitz
mesh_terms: D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D003432:Cross-Linking Reagents; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004655:Emulsions; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D058976:Folate Receptor 2 / Q000187:drug effects; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D008027:Light; D008262:Macrophage Activation / Q000502:physiology; D008264:Macrophages / Q000187:drug effects*; D018613:Microscopy, Confocal; D053769:Nanocapsules; D010078:Oxazines; D010316:Particle Size; D012542:Scattering, Radiation; D012709:Serum Albumin / Q000737:chemistry*; D013499:Surface Properties; D014966:Xanthenes
chemical_list: D003432:Cross-Linking Reagents; D004655:Emulsions; D005456:Fluorescent Dyes; D058976:Folate Receptor 2; D053769:Nanocapsules; D010078:Oxazines; D012709:Serum Albumin; D014966:Xanthenes; C005843:resazurin; D005492:Folic Acid