title: Stability and biocompatibility of a library of polyester dendrimers in comparison to polyamidoamine dendrimers.
abstract: Dendrimers can be designed for several biomedical applications due to their well-defined structure, functionality and dimensions. The present study focused on the in vitro biocompatibility evaluation of a library of aliphatic polyester dendrimers based on 2,2-bis(methylol)propionic acid (bis-MPA) with an overall diameter of 0.5-2 nm. In addition, dendrimers with two different chemical surfaces (neutral with hydroxyl end group and anionic with carboxylic end group) and dendrons corresponding to the structural fragments of the dendrimers were evaluated. Commercial polyamidoamine dendrimers (PAMAM) with cationic (amine) or neutral (hydroxyl) end group were also included for comparison. Cell viability studies were conducted in human cervical cancer (HeLa) and acute monocytic leukemia cells (THP.1) differentiated into macrophage-like cells as well as in primary human monocyte-derived macrophages. Excellent biocompatibility was observed for the entire hydroxyl functional bis-MPA dendrimer library, whereas the cationic, but not the neutral PAMAM exerted dose-dependent cytotoxicity in cell lines and primary macrophages. Studies to evaluate material stability as a function of pH, temperature, and time, demonstrated that the stability of the 4th generation hydroxyl functional bis-MPA dendrimer increased at acidic pH. Taken together, bis-MPA dendrimers are degradable and non-cytotoxic to human cell lines and primary cells.
authors.affiliation: Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Neus
authors.initials: N
authors.lastname: Feliu
authors.forename: Marie V
authors.initials: MV
authors.lastname: Walter
authors.forename: Maria I
authors.initials: MI
authors.lastname: Montañez
authors.forename: Andrea
authors.initials: A
authors.lastname: Kunzmann
authors.forename: Anders
authors.initials: A
authors.lastname: Hult
authors.forename: Andreas
authors.initials: A
authors.lastname: Nyström
authors.forename: Michael
authors.initials: M
authors.lastname: Malkoch
authors.forename: Bengt
authors.initials: B
authors.lastname: Fadeel
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D002412:Cations / Q000737:chemistry; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D050091:Dendrimers / Q000737:chemistry* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008422:Materials Testing; D015394:Molecular Structure; D011091:Polyesters / Q000737:chemistry* / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013696:Temperature
chemical_list: D001672:Biocompatible Materials; D002412:Cations; D016207:Cytokines; D050091:Dendrimers; C104700:PAMAM Starburst; D011091:Polyesters