Intravenous injection of nanoparticles as drug delivery vehicles is a common practice in clinical trials of therapeutic agents to target specific cancerous or pathogenic sites. The vascular flow dynamics of nanocarriers (NCs) in human microcapillaries play an important role in the ultimate efficacy of this drug delivery method. This article reports an experimental study of the effect of nanoparticle size on their margination and adhesion propensity in microfluidic channels of a half-elliptical cross section. Spherical polystyrene particles ranging in diameter from 60 to 970 nm were flown in the microchannels and individual particles adhered to either the top or bottom wall of the channel were imaged using fluorescence microscopy. When the number concentration of particles in the flow was kept constant, the percentage of nanoparticles adhered to the top wall increased with decreasing diameter (d), with the number of particles adhered to the top wall following a d−3 trend. When the volume concentration of particles in solution was kept constant, no discernible trend was found. This experimental finding is explained by the competition between the Brownian force promoting margination and repulsive particle–particle electrostatic forces retarding adhesion to the wall. The 970 nm particles were found to adhere to the bottom wall much more than to the top wall for each of the three physiologically relevant shear rates tested, revealing the effect of gravitational force on the large particles. These findings on the flow behavior of spherical nanoparticles in artificial microcapillaries provide further insight for the rational design of NCs for targeted cancer therapeutics.

References

References
1.
Decuzzi
,
P.
,
Pasqualini
,
R.
,
Arap
,
W.
, and
Ferrari
,
M.
,
2009
, “
Intravascular Delivery of Particulate Systems: Does Geometry Really Matter?
,”
Pharm. Res.
,
26
(
1
), pp.
235
243
.10.1007/s11095-008-9697-x
2.
Peer
,
D.
,
Karp
,
J. M.
,
Hong
,
S.
,
FaroKHzad
,
O. C.
,
Margalit
,
R.
, and
Langer
,
R.
,
2007
, “
Nanocarriers as an Emerging Platform for Cancer Therapy
,”
Nat. Nanotechnol.
,
2
(
12
), pp.
751
760
.10.1038/nnano.2007.387
3.
Hogg
,
A. J.
,
1994
, “
The Inertial Migration of Non-Neutrally Buoyant Spherical-Particles in 2-Dimensional Shear Flows
,”
J. Fluid Mech.
,
272
, pp.
285
318
.10.1017/S0022112094004477
4.
Gratton
,
S. E. A.
,
Ropp
,
P. A.
,
Pohlhaus
,
P. D.
,
Luft
,
J. C.
,
Madden
, V
. J.
,
Napier
,
M. E.
, and
DeSimone
,
J. M.
,
2008
, “
The Effect of Particle Design on Cellular Internalization Pathways
,”
Proc. Natl. Acad. Sci. U.S.A.
,
105
(
33
), pp.
11613
11618
.10.1073/pnas.0801763105
5.
Blanco
,
E.
,
Hsiao
,
A.
,
Mann
,
A. P.
,
Landry
,
M. G.
,
Meric-Bernstam
,
F.
, and
Ferrari
,
M.
,
2011
, “
Nanomedicine in Cancer Therapy: Innovative Trends and Prospects
,”
Cancer Sci.
,
102
(
7
), pp.
1247
1252
.10.1111/j.1349-7006.2011.01941.x
6.
Lee
,
S. Y.
,
Ferrari
,
M.
, and
Decuzzi
,
P.
,
2009
, “
Shaping Nano-/Micro-Particles for Enhanced Vascular Interaction in Laminar Flows
,”
Nanotechnology
,
20
(
49
). pp.
1
11
.10.1088/0957-4484/20/49/495101
7.
Drummond
,
D. C.
,
Meyer
,
O.
,
Hong
,
K. L.
,
Kirpotin
,
D. B.
, and
Papahadjopoulos
,
D.
,
1999
, “
Optimizing Liposomes for Delivery of Chemotherapeutic Agents to Solid Tumors
,”
Pharmacol Rev.
,
51
(
4
), pp.
691
743
.
8.
Barrett
,
K. B. S.
,
Boitano
,
S.
, and
Brooks
,
H.
,
2010
,
Ganong's Review of Medical Physiology
,
McGraw-Hill
,
New York
.
9.
Decuzzi
,
P.
,
Godin
,
B.
,
Tanaka
,
T.
,
Lee
,
S. Y.
,
Chiappini
,
C.
,
Liu
,
X.
, and
Ferrari
,
M.
,
2010
, “
Size and Shape Effects in the Biodistribution of Intravascularly Injected Particles
,”
J. Controlled Release
,
141
(
3
), pp.
320
327
.10.1016/j.jconrel.2009.10.014
10.
Owens
,
D. E.
, and
Peppas
,
N. A.
,
2006
, “
Opsonization, Biodistribution, and Pharmacokinetics of Polymeric Nanoparticles
,”
Int. J. Pharmaceutics
,
307
(
1
), pp.
93
102
.10.1016/j.ijpharm.2005.10.010
11.
Gao
,
H. J.
,
Shi
,
W. D.
, and
Freund
,
L. B.
,
2005
, “
Mechanics of Receptor-Mediated Endocytosis
,”
Proc. Natl. Acad. Sci. U.S.A.
,
102
(
27
), pp.
9469
9474
.10.1073/pnas.0503879102
12.
Zhang
,
S. L.
,
Li
,
J.
,
Lykotrafitis
,
G.
,
Bao
,
G.
, and
Suresh
,
S.
,
2009
, “
Size-Dependent Endocytosis of Nanoparticles
,”
Adv. Mater.
,
21
(
4
), pp.
419
424
.10.1002/adma.200801393
13.
Choi
,
H. S.
,
Liu
,
W.
,
Misra
,
P.
,
Tanaka
,
E.
,
Zimmer
,
J. P.
,
Ipe
,
B. I.
,
Bawendi
,
M. G.
, and
Frangioni
,
J. V.
,
2007
, “
Renal Clearance of Quantum Dots
,”
Nat. Biotechnol.
,
25
(
10
), pp.
1165
1170
.10.1038/nbt1340
14.
Decuzzi
,
P.
,
Gentile
,
F.
,
Granaldi
,
A.
,
Curcio
,
A.
,
Causa
,
F.
,
Indolfi
,
C.
,
Netti
,
P.
, and
Ferrari
,
M.
,
2007
, “
Flow Chamber analysis of Size Effects in the Adhesion of Spherical Particles
,”
Int. J. Nanomed.
,
2
(
4
), pp.
689
696
.
15.
Gentile
,
F.
,
Curcio
,
A.
,
Indolfi
,
C.
,
Ferrari
,
M.
, and
Decuzzi
,
P.
,
2008
, “
The Margination Propensity of Spherical Particles for Vascular Targeting in the Microcirculation
,”
Nanobiotechnology
,
6
(
9
), pp.
1
9
.10.1186/1477-3155-6-9
16.
Gentile
,
F.
,
Chiappini
,
C.
,
Fine
,
D.
,
Bhavane
,
R. C.
,
Peluccio
,
M. S.
,
Cheng
,
M. M. C.
,
Liu
,
X.
,
Ferrari
,
M.
, and
Decuzzi
,
P.
,
2008
, “
The Effect of Shape on the Margination Dynamics of Non-Neutrally Buoyant Particles in Two-Dimensional Shear Flows
,”
J. Biomech.
,
41
(
10
), pp.
2312
2318
.10.1016/j.jbiomech.2008.03.021
17.
Toy
,
R.
,
Hayden
,
E.
,
Shoup
,
C.
,
Baskaran
,
H.
, and
Karathanasis
,
E.
,
2011
, “
The Effects of Particle Size, Density and Shape on Margination of Nanoparticles in Microcirculation
,”
Nanotechnology
,
22
(
11
), pp.
1
9
.10.1088/0957-4484/22/11/115101
18.
Charoenphol
,
P.
,
Huang
,
R. B.
, and
Eniola-Adefeso
,
O.
,
2010
, “
Potential Role of Size and Hemodynamics in the Efficacy of Vascular-Targeted Spherical Drug Carriers
,”
Biomaterials
,
31
(
6
), pp.
1392
1402
.10.1016/j.biomaterials.2009.11.007
19.
Patil
,
V. R. S.
,
Campbell
,
C. J.
,
Yun
,
Y. H.
,
Slack
,
S. M.
, and
Goetz
,
D. J.
,
2001
, “
Particle Diameter Influences Adhesion Under Flow
,”
Biophys. J.
,
80
(
4
), pp.
1733
1743
.10.1016/S0006-3495(01)76144-9
20.
Fahraeus
,
R.
, and
Lindqvist
,
T.
,
1931
, “
The Viscosity of the Blood in Narrow Capillary Tubes
,”
Am. J. Physiol.
,
96
(
3
), pp.
562
568
.
21.
Munn
,
L. L.
, and
Dupin
,
M. M.
,
2008
, “
Blood Cell Interactions and Segregation in Flow
,”
Ann. Biomed. Eng.
,
36
(
4
), pp.
534
544
.10.1007/s10439-007-9429-0
22.
Jain
,
A.
, and
Munn
,
L. L.
,
2009
, “
Determinants of Leukocyte Margination in Rectangular Microchannels
,”
Plos One
,
4
(
9
), p.
e7104
.10.1371/journal.pone.0007104
23.
Abbitt
,
K. B.
, and
Nash
,
G. B.
,
2001
, “
Characteristics of Leucocyte Adhesion Directly Observed in Flowing Whole Blood in vitro
,”
Br. J. Haematol.
,
112
(
1
), pp.
55
63
.10.1046/j.1365-2141.2001.02544.x
24.
Sherwood
,
J. M.
,
Dusting
,
J.
,
Kaliviotis
,
E.
, and
Balabani
,
S.
,
2012
, “
The Effect of Red Blood Cell Aggregation on Velocity and Cell-Depleted Layer Characteristics of Blood in a Bifurcating Microchannel
,”
Biomicrofluidics
,
6
(
2
), p.
024119
.10.1063/1.4717755
25.
Damiano
,
E. R.
,
1998
, “
The Effect of the Endothelial-Cell Glycocalyx on the Motion of Red Blood Cells Through Capillaries
,”
Microvasc. Res.
,
55
(
1
), pp.
77
91
.10.1006/mvre.1997.2052
26.
Fedosov
,
D. A.
,
Caswell
,
B.
,
Popel
,
A. S.
, and
Karniadakis
,
G. E.
,
2010
, “
Blood Flow and Cell-Free Layer in Microvessels
,”
Microcirculation
,
17
(
8
), pp.
615
628
.10.1111/j.1549-8719.2010.00056.x
27.
Boso
,
D. P.
,
Lee
,
S. Y.
,
Ferrari
,
M.
,
Schrefler
,
B. A.
, and
Decuzzi
,
P.
,
2011
, “
Optimizing Particle Size for Targeting Diseased Microvasculature: From Experiments to Artificial Neural Networks
,”
Int. J. Nanomed.
,
6
, pp.
1517
1526
.10.2147/IJN.S20283
28.
Leunig
,
M.
,
Yuan
,
F.
,
Menger
,
M. D.
,
Boucher
,
Y.
,
Goetz
,
A. E.
,
Messmer
,
K.
, and
Jain
,
R. K.
,
1992
, “
Angiogenesis, Microvascular Architecture, Microhemodynamics, and Interstitial Fluid Pressure during Early Growth of Human Adenocarcinoma Ls174t in Scid Mice
,”
Cancer Res.
,
52
(
23
), pp.
6553
6560
.
29.
Lipowsky
,
H. H.
,
2005
, “
Microvascular Rheology and Hemodynamics
,”
Microcirculation
,
12
(
1
), pp.
5
15
.10.1080/10739680590894966
30.
Lowe
,
G. D. O.
,
Lee
,
A. J.
,
Rumley
,
A.
,
Price
,
J. F.
, and
Fowkes
,
F. G. R.
,
1997
, “
Blood Viscosity and Risk of Cardiovascular Events: The Edinburgh Artery Study
,”
Br. J. Haematol.
,
96
(
1
), pp.
168
173
.10.1046/j.1365-2141.1997.8532481.x
31.
Bahrami
,
M.
,
Yovanovich
,
M. M.
, and
Culham
,
J. R.
,
2006
, “
Pressure Drop of Fully-Developed Laminar Flow in Microchannels of Arbitrary Cross-Section
,”
ASME J. Fluid Eng.
,
128
(
5
), pp.
1036
1044
.10.1115/1.2234786
32.
Sharma
,
V.
,
Yan
,
Q. F.
,
Wong
,
C. C.
,
Cartera
,
W. C.
, and
Chiang
,
Y. M.
,
2009
, “
Controlled and Rapid Ordering of Oppositely Charged Colloidal Particles
,”
J. Colloid Interface Sci.
,
333
(
1
), pp.
230
236
.10.1016/j.jcis.2009.01.047
33.
Hunter
,
R. J.
,
2001
,
Foundations of Colloid Science
,
Oxford University Press
,
Oxford, UK
.
34.
Chen
,
G.
,
2005
,
Nanoscale Energy Transport and Conversion
,
Oxford University Press
,
New York
.
35.
Albanese
,
A.
,
Tang
,
P. S.
, and
Chan
,
W. C. W.
,
2012
, “
The Effect of Nanoparticle Size, Shape, and Surface Chemistry on Biological Systems
,”
Annu. Rev. Biomed. Eng.
,
14
, pp.
1
16
.10.1146/annurev-bioeng-071811-150124
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