Protective effect of PEGylation against poly(amidoamine) dendrimer-induced hemolysis of human red blood cells. 2010

Wei Wang, and Wei Xiong, and Yanhong Zhu, and Huibi Xu, and Xiangliang Yang
College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

Poly(amidoamine) (PAMAM) dendrimers are widely used in medical applications. However, dendrimers bearing positively charged surface groups are prone to destabilize cell membrane and cause cell lysis. The lytic effect of dendrimers on red blood cells (RBCs) namely hemolysis is extremely dangerous when administered in vivo. To diminish the hematologic toxicity, we modified PAMAM dendrimers with poly(ethylene glycol) (PEG) of three molecular weights (2k, 5k, and 20k). The protective effect of PEGylation against PAMAM dendrimer-induced hemolysis was studied. RBCs morphology and surface structure were analyzed by optical microscopy (OM) and atomic force microscopy (AFM). The results indicated that PAMAM and PEG-2k modified dendrimers induced hemolysis at 0.1 and 0.5 mg/mL respectively, whereas PEG-5k and PEG-20k modified dendrimers showed no significant difference in hemolysis compared with control even at 5 mg/mL. OM and AFM investigation indicated PAMAM and PEG-2k modified dendrimers caused RBCs aggregation and lysis. However, no changes were observed in the overall shape of RBCs treated with PEG-5k and PEG-20k modified dendrimers. The surface roughness of RBCs treated with PEGylated dendrimers were far lower than that of RBCs treated with PAMAM dendrimers. This study demonstrated that hemocompatibility of PAMAM dendrimers could be greatly enhanced by PEGylation.

UI MeSH Term Description Entries
D008422 Materials Testing The testing of materials and devices, especially those used for PROSTHESES AND IMPLANTS; SUTURES; TISSUE ADHESIVES; etc., for hardness, strength, durability, safety, efficacy, and biocompatibility. Biocompatibility Testing,Biocompatible Materials Testing,Hemocompatibility Testing,Testing, Biocompatible Materials,Testing, Hemocompatible Materials,Hemocompatibility Testings,Hemocompatible Materials Testing,Materials Testing, Biocompatible,Materials Testing, Hemocompatible,Testing, Biocompatibility,Testing, Hemocompatibility,Testing, Materials,Testings, Biocompatibility
D011092 Polyethylene Glycols Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS. Macrogols,Polyoxyethylenes,Carbowax,Macrogol,Polyethylene Glycol,Polyethylene Oxide,Polyethyleneoxide,Polyglycol,Glycol, Polyethylene,Glycols, Polyethylene,Oxide, Polyethylene,Oxides, Polyethylene,Polyethylene Oxides,Polyethyleneoxides,Polyglycols,Polyoxyethylene
D004903 Erythrocyte Aggregation The formation of clumps of RED BLOOD CELLS under low or non-flow conditions, resulting from the attraction forces between the red blood cells. The cells adhere to each other in rouleaux aggregates. Slight mechanical force, such as occurs in the circulation, is enough to disperse these aggregates. Stronger or weaker than normal aggregation may result from a variety of effects in the ERYTHROCYTE MEMBRANE or in BLOOD PLASMA. The degree of aggregation is affected by ERYTHROCYTE DEFORMABILITY, erythrocyte membrane sialylation, masking of negative surface charge by plasma proteins, etc. BLOOD VISCOSITY and the ERYTHROCYTE SEDIMENTATION RATE are affected by the amount of erythrocyte aggregation and are parameters used to measure the aggregation. Erythrocyte Aggregation, Intravascular,Agglutination, Intravascular,Intravascular Agglutination,Intravascular Erythrocyte Aggregation,Rouleaux Formation, Erythrocyte,Agglutinations, Intravascular,Aggregation, Erythrocyte,Aggregation, Intravascular Erythrocyte,Aggregations, Erythrocyte,Aggregations, Intravascular Erythrocyte,Erythrocyte Aggregations,Erythrocyte Aggregations, Intravascular,Erythrocyte Rouleaux Formation,Erythrocyte Rouleaux Formations,Formation, Erythrocyte Rouleaux,Formations, Erythrocyte Rouleaux,Intravascular Agglutinations,Intravascular Erythrocyte Aggregations,Rouleaux Formations, Erythrocyte
D004910 Erythrocyte Membrane The semi-permeable outer structure of a red blood cell. It is known as a red cell 'ghost' after HEMOLYSIS. Erythrocyte Ghost,Red Cell Cytoskeleton,Red Cell Ghost,Erythrocyte Cytoskeleton,Cytoskeleton, Erythrocyte,Cytoskeleton, Red Cell,Erythrocyte Cytoskeletons,Erythrocyte Ghosts,Erythrocyte Membranes,Ghost, Erythrocyte,Ghost, Red Cell,Membrane, Erythrocyte,Red Cell Cytoskeletons,Red Cell Ghosts
D004912 Erythrocytes Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN. Blood Cells, Red,Blood Corpuscles, Red,Red Blood Cells,Red Blood Corpuscles,Blood Cell, Red,Blood Corpuscle, Red,Erythrocyte,Red Blood Cell,Red Blood Corpuscle
D006461 Hemolysis The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. Haemolysis,Extravascular Hemolysis,Intravascular Hemolysis,Extravascular Hemolyses,Haemolyses,Hemolyses, Extravascular,Hemolyses, Intravascular,Hemolysis, Extravascular,Hemolysis, Intravascular,Intravascular Hemolyses
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001672 Biocompatible Materials Synthetic or natural materials, other than DRUGS, that are used to replace or repair any body TISSUES or bodily function. Biomaterials,Bioartificial Materials,Hemocompatible Materials,Bioartificial Material,Biocompatible Material,Biomaterial,Hemocompatible Material,Material, Bioartificial,Material, Biocompatible,Material, Hemocompatible
D013499 Surface Properties Characteristics or attributes of the outer boundaries of objects, including molecules. Properties, Surface,Property, Surface,Surface Property
D050091 Dendrimers Tree-like, highly branched, polymeric compounds. They grow three-dimensionally by the addition of shells of branched molecules to a central core. The overall globular shape and presence of cavities gives potential as drug carriers and CONTRAST AGENTS. Dendrimer,Dendritic Compounds,Dendritic Polymers,Dendrons,Compound, Dendritic,Dendritic Compound,Dendritic Polymer,Polymer, Dendritic,Polymers, Dendritic

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