Rheological Parameters Assessment in Serum, Plasma and Whole Blood

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J DOI: 10.4172/2157-7439.1000145 ISSN: 2157-7439 Nanomedicine & Nanotechnology

Research Article Open Access Rheological Parameters Assessment in Serum, Plasma and Whole Blood of Rats after Administration of Gold Nanoparticles of Different Sizes: In vivo Mohamed Anwar K Abdelhalim1* and Mohsen Mahmoud Mady1,2 1Department of Physics and Astronomy, College of Science, King Saud University, Saudi Arabia 2Department of Biophysics, Cairo University, 12613 Giza, Egypt

Abstract Background: The evaluation of blood rheology has been underutilised in clinical practice. We performed an array of rheological parameters measurements to quantify the responses of rat plasma, serum and whole blood to gold nanoparticles (GNPs) of different sizes. Methods: GNPs of various sizes were used in this study. Doses of 0.05 ml of the GNPs were administered to the animals via intraperitoneal injection for a period of 3 days. Blood samples with volumes of nearly 2 ml were obtained from each rat. Various rheological parameters, such as %torque, shear stress (SS), shear rate (SR), viscosity, plastic velocity, yield stress, consistency index and flow index, were measured in rat plasma, serum and whole blood. Results: The relationship between SS and SR for rat serum, plasma and whole blood showed linear behaviour with the 10, 20 and 50 nm GNPs. The viscosities of rat serum, plasma and whole blood with GNPs were decreased with increasing the SR and showed non-linear behaviour. The viscosity of blood serum and plasma was measured at a range of shear rates from 200 to 1375 s-1, while the viscosity of whole blood was measured at 75 to 600 s-1. Conclusions: The GNP size has a considerable influence on the various rheological parameters for rat blood at a fixed temperature of 37°C. The decrease in viscosity of 50 nm GNPs compared to 10 and 20 nm GNPs may be attributed to decrease in number of NPs and GNP surface area. It can be concluded that the GNPs probably cause erythrocyte deformability, and their interactions with blood proteins may cause a decrease in serum, plasma and whole blood viscosities under a given level of applied SS and SR compared to the control. This study suggests that further experimental work taking nanoparticle surface properties into consideration should be performed.

Keywords: Gold nanoparticle sizes; Serum; Plasma; Whole blood; protein. The plasma fibrinogen concentration and plasma viscosity Rheological parameters; Rats are elevated in unstable angina pectoris and stroke, and their higher values are associated with higher rates of major adverse clinical events. Introduction The elevation of plasma viscosity is correlated with the progression of Hemorheology is the study of the flow properties of blood and its coronary and peripheral artery diseases. Thus, plasma viscosity should elements (plasma and formed elements, including erythrocytes, white be measured routinely in medical practice [7]. blood cells and platelets). There is increasing evidence that the flow Nanoparticle studies are becoming much more common owing to properties of blood are among the main determinants of proper tissue their novel physical and chemical attributes in biological and medical perfusion, and alterations in these properties play significant roles in applications [8-11]. disease processes; therefore, knowledge of these properties is vital to our understanding of Hemorheology [1]. The Surface Plasmon Resonance (SPR) property of NPs allows the use of GNPs in many biological and medical applications. GNPs are Blood viscosity is determined by plasma viscosity, haematocrit used as immunostaining marker particles for electron microscopy and (volume fraction of erythrocytes, which constitutes 99.9% of the as chromophores for immunoreactions and nucleic acid hybridisation cellular elements) and the mechanical behaviour of erythrocytes. [12,13]. Their application for gene delivery into cells has also been Therefore, erythrocyte mechanics represent the major determinant reported [14-17]. In addition, GNPs have attracted attention as photo- of the flow properties of blood. Erythrocytes have unique mechanical thermal agents in hyperthermia treatment [18]. behaviours that can be discussed in terms of erythrocyte deformability and aggregation [2]. The sizes of the NPs are similar to the sizes of most biological molecules. For this reason, the GNPs can be used for both in vivo and in Whole-blood viscosity is a predictor of stroke, carotid intima-media thickening, and carotid atherosclerosis. However, in most studies, whole blood viscosity was measured at a few non-specific shear rates, and these data do not reflect the complete rheological characteristics *Corresponding author: Mohamed Anwar K. Abdelhalim, Associate Professor, found in these studies [3]. Department of Physics and Astronomy, College of Science, King Saud University, P.O. 2455, Riyadh 11451, Saudi Arabia, E-mail: [email protected]

Blood is a unique fluid. It exhibits non-Newtonian characteristics, Received May 25, 2012; Accepted July 16, 2012; Published July 18, 2012 and its viscosity is dependent on the shear rate. The major determinants Citation: Abdelhalim MAK, Mady MM (2012) Rheological Parameters of whole-blood viscosity are hematocrit, plasma viscosity, and red cell Assessment in Serum, Plasma and Whole Blood of Rats after Administration of aggregation and deformation under conditions of low and high shear Gold Nanoparticles of Different Sizes: In vivo. J Nanomed Nanotechol 3:145. rates [4-6]. doi:10.4172/2157-7439.1000145 In hyperviscosity syndromes, plasma viscosity is a better indicator Copyright: © 2012 Abdelhalim MAK, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which in follow-up examinations. In rheumatoid arthritis, sensitivity and permits unrestricted use, distribution, and reproduction in any medium, provided specificity of plasma viscosity are better than that of C-reactive the original author and source are credited.

J Nanomed Nanotechol ISSN:2157-7439 JNMNT an open access journal Volume 3 • Issue 6 • 1000145 Citation: Abdelhalim MAK, Mady MM (2012) Rheological Parameters Assessment in Serum, Plasma and Whole Blood of Rats after Administration of Gold Nanoparticles of Different Sizes: In vivo. J Nanomed Nanotechol 3:145. doi:10.4172/2157-7439.1000145

Page 2 of 5 vitro biomedical applications. Therefore, increased attention has been rheometer (cone-plate viscometer; Brookfield Engineering Laboratory, placed on the applications of NPs in biology and medicine. Incorporation, Middleboro, USA) that was supplied with a temperature bath controlled by a computer. The rheometer was guaranteed to Viscoelastic properties can be applied to the quality control of raw be accurate within ±1% of the full scale range of the spindle/speed materials, final products, and manufacturing processes. Furthermore, combination, and in-use reproducibility is within ± 0.2%. the release of a drug from a semi-solid carrier is influenced by the carrier’s rheological behaviour. The effect of certain parameters, The rheological parameters were measured at 37°C. The such as the storage time and temperature, on the quality of the temperature inside the sample chamber was carefully monitored using GNPs as pharmaceutical products can be investigated via rheological a temperature sensor during the viscosity measurements. measurements. Rheological analysis can be used as a sensitive tool in predicting the physical properties of the GNPs of different sizes. A cone and plate sensor with a diameter of 2.4 cm and an angle of 0.8 was used. The rheometer was calibrated using standard fluids. This The objective of this study was to examine the effects of the daily viscometer has a viscosity measurement range of 1.5-30,000 mPa s. intraperitoneal administration of 0.05 ml of the GNPs of different sizes (10, 20 and 50 nm) for 3 days on various rheological parameters in rat The spindle type (SC-40) and its speed combinations produce serum, plasma and whole blood over a wide range of shear rates. results with high accuracy when the applied torque is within the range of 10-100%; the appropriate spindle was chosen accordingly. Materials and Methods An aqueous solution of 0.5 ml of each size of GNP was poured into GNP sizes the sample chamber of the rheometer. The spindle was immersed and rotated in these gold nanofluids in a speed range of 20 to 180 RPM in GNPs (in sizes of the 10, 20 and 50 nm) were purchased (Product 20 minutes. The viscous drag of the GNP aqueous solution against the MKN-Au) and used in this study. The GNPs were in aqueous solution spindle was measured by the deflection of the calibrated spring. (10 mm GNPs: Product MKN-Au-010, concentration 0.01% Au; 20 nm GNPs: Product MKN-Au-020, concentration 0.01% Au; 50 nm GNPs: Statistical analysis Product MKN-Au-050, concentration 0.01% Au). The results of this study were expressed as mean ± standard Animals deviation (Mean ± SD). To assess the significance of the differences between the control group and the 3 experimental groups (G1A, G2A Healthy male Wistar-Kyoto rats (8-12 weeks old; approximately and G3A), a statistical analysis was performed using one-way analysis 250 g body weight) that were obtained from the Laboratory Animal of variance (ANOVA) for repeated measurements, with significance Centre (LAC) (College of Pharmacy, King Saud University) were assessed at the 5% confidence level. housed in pairs in humidity- and temperature-controlled ventilated cages on a 12 h day/night cycle. A rodent diet and water were provided. Results and Discussions Fifty rats were individually caged and divided into the control group (NG: n=8), group 1 (A: infusion of the 20 nm GNPs for 3 days; n=6), Rheological parameters measurements group 2 (A: infusion of the 10 nm GNPs for 3 days; n=6) and group 3 This study is unique in examining the relationships between various (A: infusion of the 50 nm GNPs for 3 days; n=6). All experiments were rheological parameters in rat plasma, serum and whole blood after conducted in accordance with the guidelines approved by King Saud the administration of 0.05 ml of the GNPs of various sizes at a fixed University Local Animal Care and Use Committee. temperature of 37ºC and a wide range of shear rates using a Brookfield GNPs administration and preparation of serum, plasma and LVDV-III Programmable rheometer. whole blood The data in the present study suggest that at these shear rates, Doses of 0.05 ml of the GNPs (10, 20 and 50 nm) in aqueous serum, plasma and whole blood viscosities are influenced by the size solutions were administered to the animals via intraperitoneal and shape of the administered GNPs, the number of NPs and the GNP administration for a period of 3 days. The rats were anesthetised by surface area. inhalation of 5% isoflurane until muscular tonus relaxed. Blood and The viscosities of blood serum and plasma were measured ata several organs (liver, heart, lung and kidney) were collected from each shear rate range of 200 to 1375 s-1, while the viscosity of whole blood rat. was measured at a shear rate range of 75 to 600 s-1. The shear stress (SS) Blood samples of nearly 2 ml were collected into three polypropylene and shear rate (SR) of G1A (20 nm), G2A (10 nm) and G3A (50 nm) tubes: the 1st tube for serum, the 2nd tube for plasma and the 3rd tube for for plasma, serum and whole blood were linearly related as shown in whole blood. The serum was prepared by allowing the blood to clot at Figures 1, 3 and 5, and the SS and SR relationships of serum, plasma 37°C. The blood was then centrifuged at 3,000 rpm for ten minutes. The and whole blood can be written as shown in Table 1. blood for plasma was collected in EDTA. Whole blood was prepared by The viscosities of rat serum, plasma and whole blood with the 50 adding 0.8 ml of heparin to 0.8 ml of collected blood. nm GNPs were significantly lower than those with the 10 nm GNPs. Experimental setup and rheological parameters The decrease in viscosity of the 50 nm GNP solutions may be attributed to the decrease in the number of GNPs and decreased GNP surface The following experimental setup was used to measure several area. For all of the GNPs, the highest viscosity values were observed rheological parameters in rat serum, plasma and whole blood after for whole blood compared to plasma and serum as shown in Figures the administration of the 10, 20 and 50 nm GNPs. The rheological 2, 4 and 6. parameters tested were viscosity, %torque, Shear Stress (SS), Shear Rate (SR), plastic viscosity, yield stress, and consistency index. These The viscosities of rat serum, plasma and whole blood with the10, 20 parameters were measured using a Brookfield LVDV-III Programmable and 50 nm GNPs were decreased with increasing the SR. The viscosity

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This study suggests that the decrease in serum, plasma and whole Blood Plasma at shear rate (SR): 200-1375 s-1 blood viscosities with the 10, 20 and 50 nm GNPs may be attributed 20 SStress 10 nm, to the decrease in haematocrit and cytoplasmic haemoglobin 2 18 Y = 0.01418 * X , R = 0.99997, SD = 0.07672 concentration of erythrocytes, erythrocyte deformability (degree of SStress 20 nm 16 2

) Y = 0.01427 * X , R = 0.99999 , SD = 0.14339 2

m 14

c SStress 50 nm / -1 Y = B * X , R2 = 0.99998 , SD = 0.09183 1.55 ne 12 Blood serum at shear rate (SR): 200-1375 s y d ( 10 1.50 Vis 10 nm , R2 = 0.98034 , SD = 0.0013 ss -4 -7 2 -11 3 e

r Y = 1.4702 - 1.2722 *X + 1.3081 *X - 5.3393 *X t 8 s

r 1.45 6 hea

S 1.40 4 ) p c ( 2 y

t 1.35 i

s 2

0 o Vis 20 nm , R = 0.96112 , SD = 0.00443 -4 -7 2 -10 3 sc

0 200 400 600 800 1000 1200 1400 i 1.30 Y = 1.3607 - 3.2574 *X + 3.2063 *X - 1.0532 *X V Shear rate s-1 1.25 Figure 1: The relationship between shear stress and shear rate for blood plasma of rat at shear rate range of 200-1375 s-1. 1.20 Vis 50 nm , R2 = 0.91511 , SD = 0.00485 Y = 1.2955 - 1.7599-4*X + 1.5648-4*X2 - 4.8918-11*X3 1.15 200 400 600 800 1000 1200 1400 -1 Blood Plasma at shear rate (SR): 200-1375 s-1 Share rate s 1.51 Vis 10 nm , R2 = 0.9803 , SD = 0.00183 Figure 4: The relationship between viscosity and shear rate for blood serum of -4 -7 2 -11 3 1.50 Y = 1.470 - 1.272 *X + 1.308 *X - 5.339 *X rat at shear rate range of 200-1375 s-1. 1.49 Vis 20 nm , R2 = 0.9942, SD = 0.0273 -4 -7 2 -11 3 1.48 Y = 1.5608 - 3.069 *X + 2.234 *X - 6.058 *X 1.47 Vis 50 nm, R2 = 0.98721, SD = .00223 -4 -7 2 -11 3 Y = 1.471 - 1.822 *X + 1.3069 *X - 3.379 *X 22 -1 ) 1.46

p Whole blood at shear rate (SR):75-600 s c

( 1.45 20

y t

i 1.44 2

s 18 SStress 10 nm , R = 0.99967 , SD = 0.16202 o 1.43 c Y = 1.41048 + 0.03166 * X s )

i 16 1.42 2 V m

c 14 1.41 /

1.40 ne y 12 d (

1.39 10 1.38 ss e r t 8 1.37 s

200 400 600 800 1000 1200 1400 r 6 SStress 20 nm , R2 = 0.99858 , SD = 0.26071

-1 hea

S Y = 2.06193 + 0.02459 * X Share rate s 4 SStress 50 nm , R2 = 0.99943 , SD = 0.18224 Figure 2: The relationship between viscosity and shear rate for blood plasma 2 Y = 1.45616 + 0.0273 * X of rat at shear rate range of 200-1375 s-1. 0 0 100 200 300 400 500 600 Shear rate s-1

20 -1 Blood serum at shear rate (SR): 200-1375 s Figure 5: The relationship between shear stress and shear rate for whole -1 18 blood of rat at shear rate range of 75-600 s . 2 16 SStress 10 nm , R = 0.99997

) Y = 0.01418 * X , SD = 0.07672 2 2 m 14

c SStress 20 nm , R = 0.99997 / Y = 0.01251 * X , SD = 0.07306

ne 12 -1 y 2 5.0 Whole blood at shear rate (SR):75-600 s

d SStress 50 nm , R (

10 Y = 0.01227 * X , SD = 0.0703 Vis 10 nm , R2 = 0.99725 , SD = 0.03099 ss 2 3 e

r Y = 5.4117 - 0.0115*X + 2.4239*X - 1.7937*X t 8 s 4.5 2 r Vis 20 nm , R = 0.9951 , SD = 0.05948 6 2 3 Y = 5.647 - 0.01597*X + 3.2779*X - 2.37396*X hea S 4 2 ) 4.40 Vis 50 nm , R = 0.9983 , SD = 0.02436 p 2 3 c

( Y = 4.8789 - 0.00987*X + 1.8344*X - 1.2061*X 2 y t i s

0 o

c 3.5 s

0 200 400 600 800 1000 1200 1400 i V Shear rate s-1 3.0 Figure 3: The relationship between shear stress and shear rate for blood serum of rat at shear rate range of 200-1375 s-1.

2.5 0 100 200 300 400 500 600 and SR relationships of rat serum, plasma and whole blood with the10, Share rate s-1 20 and 50 nm GNPs were non-linearly related as shown in Figures 2, Figure 6: The relationship between viscosity and shear rate for whole blood of 4 and 6. rat at shear rate range of 75-600 s-1.

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Plasma (shear rate range: 200-1375s-1) 10 nm GNPs: SS = 0.01418 *SR R2= 0.999 SD = 0.0767

20 nm GNPs: SS = 0.01427*SR R2= 0.999 SD = 0.1434

50 nm GNPs: SS = 0.01418 *SR R2= 0.999 SD = 0.0918 Serum(shear rate range: 200-1375s-1) 10 nm GNPs: SS = 0.01418 *SR R2= 0.999 SD = 0.0767

20 nm GNPs: SS = 0.01251 *SR R2= 0.999 SD = 0.0731

50 nm GNPs: SS = 0.01227 *SR R2= 0.999 SD = 0.0703 Whole blood(shear rate range: 75-600s-1) 10 nm GNPs: SS = 1.41 + 0.03*SR R2= 0.999 SD = 0.16

20 nm GNPs: SS = 2.06 + 0.03*SR R2= 0.999 SD = 0.261

50 nm GNPs: SS = 1.46 + 0.027*SR R2= 0.999 SD = 0.182 Table 1: The relationship between shear stress and shear rate for plasma, serum and whole blood of rat at wide range of shear rate. shape change under a given level of applied shear stress and shear rate), GNPs strongly associate with essential blood proteins, where and the changes induced in the viscoelastic properties of erythrocyte the binding constant and degree of cooperatively of particle−protein membranes. binding depends on the particle size and the native protein structure. Moreover, the thickness of the adsorbed protein layer (bare NP Plasma viscosity is determined by the water content and diameter <50 nm) progressively increases with the NP size, which macromolecular components of plasma, so the factors that affect blood causes effects that have potential importance for understanding the viscosity are the plasma protein concentration and the types of proteins general NP aggregation in biological media and the interactions of NP present in the plasma. However, these effects are minor compared to the with biological materials [21]. effect of hematocrit, so they are effectively insignificant. An elevation of plasma viscosity correlates with the progression of coronary and In this manuscript the author used GNPs with three different peripheral vascular diseases. Anaemia can lead to decreased blood sizes that are available commercially as models for rheological study. viscosity, which may lead to heart failure [19]. However, it is not clear that the surface properties of the GNPs are critically important influencing the interaction with the proteins in the The shape change of erythrocytes under applied forces is reversible, and the biconcave-discoid shape, which is normal for most mammals, blood. Illustration on the surface properties would help to gain deeper is maintained after the removal of the deforming forces. In other words, insight into interactions between GNPs and blood, thus the rheological erythrocytes behave like elastic bodies, but they also resist shape change behaviour of blood and GNPs is relevant. Therefore, this study suggests under the influence of deforming forces. This viscoelastic behaviour of that further experimental work taking nanoparticle surface properties erythrocytes is determined by the following three properties: 1) their into consideration should be performed. biconcave-discoid geometric shape provides extra surface area for the Conclusions cell, enabling shape changes without increasing the surface area; this type of shape change requires significantly smaller forces than those This study indicates that GNP size has a considerable influence on required for shape changes with surface area expansion; 2) cytoplasmic the various rheological parameters measured in rat serum, plasma and viscosity, which reflects the cytoplasmic haemoglobin concentration whole blood at 37°C. of erythrocytes; and 3) the viscoelastic properties of the erythrocyte The decrease in viscosity of blood fluids in the presence of the 50 membrane, which are mainly determined by their special membrane nm GNPs compared to the 10 and 20 nm GNPs may be attributed to skeletal network [20]. the decrease in the number of GNPs and the decreased GNP surface The effect of a protein on plasma viscosity depends on its molecular area. weight and structure. A less spheroid shape, higher molecular weight, The viscosities of rat serum, plasma and whole blood with the10, 20 higher aggregating capacity, and higher temperature or pH sensitivity of and 50 nm GNPs were decreased with increasing the SR. The viscosity a protein will lead to higher plasma viscosity [7]. Plasma is a Newtonian and SR relationships of rat serum, plasma and whole blood with the10, fluid, and its viscosity does not depend on flow characteristics. Its 20 and 50 nm GNPs showed non-linear behaviour. For all of the GNPs, normal value is 1.10-1.30 mPa s at 37°C, which is independent of age the highest viscosity values were observed in whole blood compared to and gender [7]. The measurement has high stability and accuracy, so plasma and serum. the detection of small alterations may be pathologically important. Inflammation and tissue injuries resulting in changes in plasma Based on the present results of erythrocyte rheological properties, proteins can increase its value with high sensitivity but low specificity it can be concluded that the GNPs would probably cause erythrocyte [19-21]. deformability.

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Authors’ Contributions 10. Tokonami S, Shiigi H, Nagaoka T (2008) Preparation of nanogapped gold nanoparticle array for DNA detection. Electroanalysis 20: 355-360. AMAK analysed data and interpreted and wrote the final draft of this manuscript. The animal model used in this study was obtained from the Laboratory 11. Huang X, Jain PK, El-Sayed IH, El-Sayed MA (2007) Gold nanoparticles: Animal Centre (College of Pharmacy, King Saud University). AMAK conceived the interesting optical properties and recent applications in cancer diagnostics and plan and design and obtained research grants for this study. The authors have read therapy. Nanomedicine 2: 681-693. and approved the final manuscript. 12. Mirkin CA, Letsinger RL, Mucic RC, Storhoff JJ (1996) A DNA-based method for rationally assembling nanoparticles into macroscopic materials. Nature 382: Acknowledgements 607-609. The authors are very grateful to NPST. This research was financially supported 13. Huber M, Wei TF, Muller UR, Lefebvre PA, Marla SS, et al. (2004) Gold by the National Science and Technology Innovation Plan (NSTIP), Research No. nanoparticle probe-based gene expression analysis with unamplified total 08-ADV206-02 and Research No. 09-NAN670-02, College of Science, King Saud human RNA. Nucleic Acids Res 32: e137. University, Saudi Arabia. 14. Ow Sullivan MM, Green JJ, Przybycien TM (2003) Development of a novel References gene delivery scaffold utilizing colloidal gold-polyethylenimine conjugates for DNA condensation. Gene Ther 10: 1882-1890. 1. Baskurt OK (2007) Handbook of hemorheology and hemodynamics. IOS Press, Amsterdam, Netherlands. 15. Sandhu KK, McIntosh CM, Simard JM, Smith SW, Rotello VM (2002) Gold nanoparticle-mediated transfection of mammalian cells. Bioconjug Chem 13: 2. Baskurt OK, Meiselman HJ (2003) Blood rheology and hemodynamics. Semin 3-6. Thromb Haemost 29: 435-450. 16. Niidome T, Nakashima K, Takahashi H, Niidome Y (2004) Preparation of 3. Baskurt OK, Boynard M, Cokelet GR, Connes P, Cooke BM, et al. (2009) primary amine-modified gold nanoparticles and their transfection ability into New guidelines for hemorheological laboratory techniques. Clin Hemorheol cultivated cells. Chem Commun (Camb) 1978-1979. Microcirc 42: 75-97. 17. Kawano T, Yamagata M, Takahashi H, Niidome Y, Yamada S, et al. (2006) 4. Koenig W, Ernst E (1992) The possible role of hemorheology in Stabilizing of plasmid DNA in vivo by PEG-modified cationic gold nanoparticles atherothrombogenesis. Atherosclerosis 94: 93-107. and the gene expression assisted with electrical pulses. J Control Release 111: 5. Dutta A, Tarbell JM (1996) Influence of non-Newtonian behavior of blood on 382-389. flow in an elastic artery model. J Biomech Eng 118: 111-119. 18. El-Sayed IH, Huang X, El-Sayed MA (2006) Selective laser photo-thermal 6. Goldsmith HL, Turitto VT (1986) Rheological aspects of thrombosis and therapy of epithelial carcinoma using anti-EGFR antibody conjugated gold haemostasis: basic principles and applications. ICTH-Report--subcommittee nanoparticles. Cancer Lett 239: 129-135. on rheology of the international committee on thrombosis and haemostasis. 19. Tefferi A (2003) A contemporary approach to the diagnosis and management Thromb Haemost 55: 415-435. of polycythemia vera. Curr Hematol Rep 2: 237-241. 7. Késmárky G, Kenyeres P, Rábai M, Tóth K (2008) Plasma viscosity: a forgotten 20. Chien S (1987) Red cell deformability and its relevance to blood flow. Annual variable. Clin Hemorheol Microcirc 39: 243-246. Rev Physiol 49: 177-192. 8. Sperling RA, Gil PR, Zhang F, Zanella M, Parak WJ (2008) Biological 21. Lacerda SH, Park JJ, Meuse C, Pristinski D, Becker ML, et al. (2010) Interaction applications of gold nanoparticles. Chem Soc Rev 37: 1896-1908. of gold nanoparticles with common human blood proteins. ACS Nano 4: 365- 9. Wan H, Chen L, Chen J, Zhou H, Zhang D, et al. (2008) Synthesis and 379. fluorescence property of the gold nanoparticles modified with 9-Methyl-9-(8- thiooctyl)-fluorene. J Dispers Sci Technol 29: 999-1002.

J Nanomed Nanotechol ISSN:2157-7439 JNMNT an open access journal Volume 3 • Issue 6 • 1000145