title: Cytotoxicity and biodistribution studies on PEGylated EDA and PEG cored PAMAM dendrimers.
abstract: Starting from Ethylenediamine (EDA) or poly(ethylene glycol) tetra amine (4-arm-PEG) cores, two different peripheral methylester (-COOCH3) or amine (-NH2) PAMAM dendrimers have been synthesized. In the growth phase of dendrimers, two important building blocks, methyl acrylate for the half generation and EDA for the full generations, have been used. In order to improve the yield and decrease the time for the aminolysis step, a microwave-assisted technique was applied. Both of these dendrimers with different cores were grown up to 4.5 generations where surface modification, i.e. PEGylation, with 10% Poly(ethylene glycol) bis(amine) was performed. In order to increase the solubility of dendrimers, esteric surfaces were converted to carboxylic acid groups. Accordingly, the dendrimers were soluble in water or in water-methanol mixture which enabled their purification by liquid-phase polymer-based retention in each step. Finally, the resulting products that were characterized with (NMR and FTIR) spectroscopy were evaluated in vitro and in vivo. The analytical grade dendrimers were not cytotoxic to mouse fibroblasts and their biodistribution was mainly determined in the site of injection (peritoneum), liver and kidneys.
authors.affiliation: a Faculty of Arts and Sciences, Department of Chemistry , Yıldız Technical University , Istanbul , Turkey.
authors.forename: Mustafa U
authors.initials: MU
authors.lastname: Gürbüz
authors.affiliation: b Faculty of Pharmacy, Department of Pharmaceutical Technology , Hacettepe University , Ankara , Turkey.
authors.forename: Kıvılcım
authors.initials: K
authors.lastname: Öztürk
authors.affiliation: c Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences , Adıyaman University , Adıyaman , Turkey.
authors.forename: Ali S
authors.initials: AS
authors.lastname: Ertürk
authors.affiliation: d Department of Basic Oncology , Hacettepe University Cancer Institute , Ankara , Turkey.
authors.forename: Digdem
authors.initials: D
authors.lastname: Yoyen-Ermis
authors.affiliation: d Department of Basic Oncology , Hacettepe University Cancer Institute , Ankara , Turkey.
authors.forename: Gunes
authors.initials: G
authors.lastname: Esendagli
authors.affiliation: b Faculty of Pharmacy, Department of Pharmaceutical Technology , Hacettepe University , Ankara , Turkey.
authors.forename: Sema
authors.initials: S
authors.lastname: Çalış
authors.affiliation: a Faculty of Arts and Sciences, Department of Chemistry , Yıldız Technical University , Istanbul , Turkey.
authors.forename: Metin
authors.initials: M
authors.lastname: Tülü
mesh_terms: D000818:Animals; D002460:Cell Line; D050091:Dendrimers / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D005029:Ethylenediamines / Q000737:chemistry*; D005260:Female; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D050091:Dendrimers; D004337:Drug Carriers; D005029:Ethylenediamines; C104700:PAMAM Starburst; D011092:Polyethylene Glycols; C031234:ethylenediamine
keywords: Dendrimer; PAMAM; PEGylation; biodistribution; cytotoxicity