Table 7.

Studies on the successful preparation of blood-compatible dendrimers.

Components or strategy	Route	Drug or purpose	Assessment format	Observations	Ref.
The triblock dendrimer: polyamidoamine-polyethylene glycol-cyclic RGD	–	–	Hemolysis Plasma clotting Platelet aggregation test Complement activation test	The preparation has only a minor effect on red blood cells. All the other evaluated parameters are also within the acceptable range.	[152]
Cationic PAMAM dendrimer of generation 4.0 (PM4.0) were functionalized by PEG conjugation or by thiolation or the combination of both methods.	–	–	Hemolysis Complement activation test Plasma clotting Platelet aggregation test	The degree of hemolysis in all formulations is within an acceptable range. Compared with unmodified PM4.0, the thiolation of PM4.0 does not reduce the production of c3a, and compared with unmodified PM4.0, the modification of PM4.0 with PEG alone will moderately reduce the production of c3a. When the PEGylation ratio is increased from 1.8 to 4.0, this effect is more obvious. PM4.0 and PEGylated PM4.0 dendrimers produce higher PT values. Compared with the original PM4.0, PEGylated PM4.0 alone showed a shorter PT, and the effect was more obvious when the PEG ratio was increased. In contrast, bifunctionalized PM4.0 dendrimers and PM3.5 cannot regulate the external coagulation pathway. Similar to PT determination, citrate human plasma treated with various dendrimers showed APTT prolongation or no clotting. Unmodified PM4.0 and PEG-modified PM4.0 showed long-term coagulation exceeding 0.125 mg/ml. The effect of PEGylated and bifunctionalized PM4.0 on collagen-induced platelet aggregation is reduced, suggesting its anticoagulant properties.	[153]
Lysine-Cbz (Lys-Cbz) or Arginine-Tos (Arg-Tos) coupled PAMAM G4 dendrimers	–	Antithrombotic drug or a drug delivery vehicle	Hemolysis Platelet aggregation assay Platelet secretion assay Analysis of platelet adhesion	The proportion of hemolysis of PAMAM dendrimers G4, G4-Lys-Cbz and G5 (concentration of 0.25 mg/ml) were 9.8%, 8.7% and 6.6% respectively. The commercially available PAMAM G4 and G5 dendrimers cause strong aggregation of RBC, while the interaction between PAMAM G4 derivatives and RBC is not large. PAMAMG5 derivatives show moderate RBC agglutination. PAMAM G4 showed only 2% ± 1% inhibition of platelet aggregation. G4-Arg-Tos inhibited platelet secretion in an order of 25% ± 12% (P <0.05). After incubating G4-Arg-Tos in whole blood, platelet coverage was suppressed by 74%. In contrast, PAMAM G5 and its derivatives have no effect on platelet function. Both PAMAM G4-Arg-Tos and G4-Lys-Cbz are effective inhibitors of platelet aggregation induced by ADP. G4-Arg-Tos showed inhibition of platelet secretion.	[8]
Cationic G4 PAMAM dendrimers	p.o.	Risperidone	Hemolysis	The preparation has no significant effect on red blood cells.	[154]
PEG (molecular weight 5000) was conjugated to G5 and G6 PAMAM dendrimers	i.m.	Gene delivery	Hemolysis	The hemolysis percentage of G5-PEG and G6-PEG was significantly reduced to about 5% (P <0.005). The hemolysis of 2.5 mg/ml PEG-PAMAM dendrimer at high PEG conjugation of 15% was not significantly different from that of 8% PEG conjugation.	[155]