We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Dual-functionalized poly(amidoamine) dendrimers with poly(ethylene glycol) conjugation and thiolation improved blood compatibility.
- Authors
Liu, Yuanjie; Pang, Yanzhen; Toh, Ming R.; Chiu, Gigi N. C.
- 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.
- Subjects
DENDRIMERS synthesis; DENDRIMERS in medicine; BLOOD products; BIOCOMPATIBILITY; PROTHROMBIN
- Publication
Journal of Pharmacy & Pharmacology, 2015, Vol 67, Issue 11, p1492
- ISSN
0022-3573
- Publication type
Article
- DOI
10.1111/jphp.12457