The effects of size and period of administration of gold nanoparticles on rheological parameters of blood plasma of rats over a wide range of shear rates: in vivo.

BACKGROUND: Blood viscosity appears to be independent predictor of stroke, carotid intima-media thickening, atherosclerosis and most cardiovascular diseases. In an attempt to understand the toxicity and the potential threat of GNPs therapeutic and diagnostic use, an array of rheological parameters were performed to quantify the blood plasma response to different sizes and administration periods of GNPs over a wide range of shear rates.

METHODS: Healthy, thirty male Wistar-Kyoto rats, 8-12 weeks old (approximately 250 g body weight) were divided into control group (NG: n = 10), group 1 (G1A: intraperitoneal infusion of 10 nm GNPs for 3 days, n = 5 and G1B: intraperitoneal infusion of 10 nm GNPs for 7 days, n = 5), group 2 (G2A: intraperitoneal infusion of 50 nm GNPs for 3 days, n = 5 and G2B: intraperitoneal infusion of 50 nm GNPs for 7 days, n = 5). Dose of 100 μl of GNPs was administered to the animals via intraperitoneal injection. Blood samples of nearly 1 ml were obtained from each rat. Various rheological parameters such as torque, shear stress, shear rate, viscosity, plastic velocity, yield stress, consistency index (k) and flow index (n) were measured in the blood plasma of rats after the intraperitoneal administration of 10 and 50 nm GNP for 3 and 7 days using Brookfield LVDV-III Programmable rheometer.

RESULTS: The relationship between shear stress and shear rate for control, G1A, G1B, G2A and G2B was linearly related. The plastic viscosity and the yield stress values for G1A, G1B, G2A and G2B significantly (p < 0.05) decreased compared with the control. The n and k values calculated from equation (1). The k values for G1A, G1B and G2B decreased compared with the control; however the means were not significantly different. While G2A indicates no significant change compared with the control. The values of the flow behaviour index (n) were equal ≤ 1 for all the different GNPs sizes. The viscosity values measured for 10 and 50 nm GNPs (G1A, G1B, G2A and G2B) decreased compared with the control; however the means were not significantly different. The decrease in blood plasma viscosity values observed with all GNPs is particle size and administration period independent.

CONCLUSIONS: At these particular shear rates, the estimated rheological parameters are not influenced by GNPs size and shape, number of NPs, surface area and administration period of GNPs. This study demonstrates that the highly decrease in blood plasma viscosity was accompanied with the smaller 10 nm GNPs compared with the 50 nm GNPs. The decrease in blood plasma viscosity induced with 10 and 50 nm GNPs may be attributed to decrease in hematocrit and haemoglobin concentration in addition to erythrocyte deformability. This study suggests that histomorphologcal, histochemical and ultrastrucural investigations are needed to evaluate the inflammations and tissue injuries, in relation to the application of GNPs as a therapeutic and diagnostic tool.