title: Dual-functionalized poly(amidoamine) dendrimers with poly(ethylene glycol) conjugation and thiolation improved blood compatibility.
abstract: OBJECTIVE
  This study aims to examine the blood compatibility of dual-functionalized poly(amidoamine) (PAMAM) dendrimers.
  
  
  METHODS
  The cationic PAMAM dendrimer of generation 4.0 (PM4.0) were functionalized by poly(ethylene glycol) (PEG) conjugation or by thiolation or the combination of both methods. Various in-vitro assays including immune cell cytotoxicity, haemoglobin release, serum albumin binding, complement activation and coagulation times were used to characterize the compatibility with blood components.
  
  
  RESULTS
  Although thiolation of polymers has been reported as a strategy to reduce platelet activation or aggregation, thiolation of PM4.0 alone did not offer any protective effect against the dendrimer toxicity on blood components or functions. PEGylation was able to reduce the toxic effect and interactions of the unmodified and thiolated PM4.0 on various blood components and functions; yet, PEGylated PM4.0 displayed prolonged prothrombin times and activated partial thromboplastin times. Among various PM4.0 derivatives, dual-functionalized PM4.0 with PEG and thiol groups displayed the least toxicity to various blood components and functions.
  
  
  CONCLUSIONS
  Our findings suggested that comprehensive studies of dendrimer biocompatibility should be performed so as to establish the safe dose window for systemic administration.
authors: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore.
authors: Yuanjie
authors: Y
authors: Liu
authors: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore.
authors: Yanzhen
authors: Y
authors: Pang
authors: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore.
authors: Ming R
authors: MR
authors: Toh
authors: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore.
authors: Gigi N C
authors: GN
authors: Chiu
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000187:drug effects*; D001777:Blood Coagulation / Q000187:drug effects*; D050091:Dendrimers / Q000737:chemistry / Q000633:toxicity*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D010314:Partial Thromboplastin Time; D011092:Polyethylene Glycols / Q000737:chemistry*; D011485:Protein Binding; D011517:Prothrombin Time; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry; D020298:U937 Cells
chemical_list: D050091:Dendrimers; D006454:Hemoglobins; C104700:PAMAM Starburst; D012709:Serum Albumin; D013438:Sulfhydryl Compounds; D011092:Polyethylene Glycols
keywords: blood compatibility; poly(amidoamine) dendrimer; poly(ethylene glycol) (PEG) conjugation (PEGylation); thiolation