Blood compatibility of polyamidoamine dendrimers and erythrocyte protection.
Dendrimers are global macromolecules with promising biomedical application. In order to investigate their blood compatibility, different generations of polyamidoamine (PAMAM) dendrimers terminated with different types of surface functional groups were incubated with red blood cells (RBC) for time course of haemolysis assay and RBC morphology observation. Cationic PAMAM dendrimers demonstrated obvious generation, concentration and time dependent haemolysis while anionic and neutral PAMAM dendrimers were much less hemolytic. The surface amino groups and the polymeric structure of cationic PAMAM dendrimers played pivotal roles in haemolysis induction; meanwhile the basic pH of cationic PAMAM solutions was an inneglectable factor. Due to the presence of plasma proteins in abundance, whole blood was found tolerable to haemolysis induced by dendrimers, possibly through complex formation of plasma proteins with cationic PAMAM dendrimers. It was deduced that poly-carboxylic acids may have the similar effect as that of plasma proteins. So by means of pH adjustment to the physical 7.4, reduction of administration dose and the combined use of plasma protein (or other protective additives such as negatively charged molecules), the blood compatibility and even biocompatibility of cationic dendrimers may be enhanced to "safe" level.
Han
Mei-Hua
MH
Chinese Academy of Medical Sciences and Peking Union Medical College Institute of Medicinal Plant Development, Beijing 100094, China.
Chen
Jing
J
Wang
Jian
J
Chen
Shi-Lin
SL
Wang
Xiang-Tao
XT
D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology*; D002412:Cations / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008422:Materials Testing; D008853:Microscopy
D001672:Biocompatible Materials; D002412:Cations; D050091:Dendrimers; C104700:PAMAM Starburst