Affiliation:
1. Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore
Abstract
Abstract
Objectives
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.
Key findings
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.
Funder
National University of Singapore
NUS President Graduate Fellowship
Publisher
Oxford University Press (OUP)
Subject
Pharmaceutical Science,Pharmacology
Cited by
18 articles.
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