title: Anionic linear-globular dendrimers: biocompatible hybrid materials with potential uses in nanomedicine.
abstract: The use of dendrimers as nano-sized excipients/vectors in biological and pharmaceutical systems is dependent on the investigation of their toxicological profiles in biological media. In this study, a series of mechanistic in vitro structure-associated cell toxicity evaluations was performed on the two generations of an anionic linear-globular dendrimer G1 and G2 (where PEG is the core, and citric acid is the periphery) each of which has a different size, charge, and MW. In vitro cytotoxicity behavior of the dendrimers with the methods like crystal violet staining, methyl thiazolyl tetrazolium (MTT), and lactate dehydrogenase (LDH) assays was analyzed. The cell death mechanisms (apoptosis-necrosis) induced by the dendrimers were also evaluated in HT1080 cell line. The impact of the dendrimers on the release of the pro-inflammatory cytokines like TNF-alpha (tumor necrosis factor alpha) and IL1-beta (interleukin 1 beta) was assessed in THP-1 cell line. Hemolysis assay and coagulation studies such as PT (prothrombin time) and APTT (activated partial thromboplastin time) on human blood samples were conducted to examine the interactions of the dendrimers with such bio-environments. The results of cell cytotoxicity experiments and the amounts of IL1-beta and TNF-alpha secretions from THP-1 cell line were consistent with the hemoglobin release from the erythrocytes and the results gained from the coagulation studies. In fact, no significant harmful effect was observed for the dendrimers up to the concentration of 0.5 mg/ml. Both apoptosis and necrosis were ascribed to cell death. The G1 with more flexibility, less negative charge, and greater poly dispersity in size versus the G2 displayed more toxicity than the G2 at the concentration of 1 mg/ml and above in most of the experiments. As a whole, these results suggest a biocompatible range for these hybrid structures up to the concentration of 0.5 mg/ml. Therefore, the potentiality for these structures to be employed in the different and numerous realms of nanomedicine will be very great.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Shafiee
authors.initials: MS
authors.lastname: Alavidjeh
authors.forename: Ismaeil
authors.initials: I
authors.lastname: Haririan
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Khorramizadeh
authors.forename: Zohre Zarei
authors.initials: ZZ
authors.lastname: Ghane
authors.forename: Mehdi Shafiee
authors.initials: MS
authors.lastname: Ardestani
authors.forename: Hassan
authors.initials: H
authors.lastname: Namazi
mesh_terms: D000818:Animals; D000838:Anions / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004906:Erythrocyte Count; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008422:Materials Testing; D008954:Models, Biological; D008968:Molecular Conformation; D050997:Nanomedicine / Q000295:instrumentation / Q000379:methods*; D010314:Partial Thromboplastin Time
chemical_list: D000838:Anions; D001672:Biocompatible Materials; D050091:Dendrimers