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The relationship between pH and zeta potential of 30 nm metal oxide nanoparticle suspensions relevant to in vitro toxicological evaluations


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Zeta potential measurements are common in nanotoxicology. This research probes the effects of pH and time on nanoparticle zeta potential, agglomerate size, and cellular viability. The nanoparticles TiO2, Fe2O3, Al2O3, ZnO, and CeO2, were titrated from pH 12.0–2.0. The isoelectric points (IEP) of the nanoparticles were near neutral with the exception of TiO2 (IEP = 5.19) and Fe2O3 (IEP = 4.24). Nanoparticle agglomerates were largest at the IEP. TiO2 and Fe2O3 increased in zeta potential and agglomerate size over time; while Al2O3 and ZnO displayed little change. CeO2 increased in zeta potential; however, the net charge remained negative. Cytotoxicity studies revealed that TiO2 and Fe2O3 caused decreasing cellular viability over 48 h. Al2O3, ZnO, and CeO2 cellular viability remained similar to control. Results indicate that alterations in the pH have a large effect on zeta potential and agglomerate size which may be used as a predictive measure of nanotoxicity.
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Nanotoxicology, December 2009; 3(4): 276283
The relationship between pH and zeta potential of ~30 nm metal oxide
nanoparticle suspensions relevant to in vitro toxicological evaluations
Department of Veterinary Physiology & Pharmacology, Texas A&M University, College Station, Texas, USA
(Received 30 April 2009; accepted 19 August 2009)
Zeta potential measurements are common in nanotoxicology. This research probes the effects of pH and time on nanoparticle
zeta potential, agglomerate size, and cellular viability. The nanoparticles TiO
, ZnO, and CeO
, were titrated
from pH 12.02.0. The isoelectric points (IEP) of the nanoparticles were near neutral with the exception of TiO
(IEP =5.19)
and Fe
(IEP =4.24). Nanoparticle agglomerates were largest at the IEP. TiO
and Fe
increased in zeta potential and
agglomerate size over time; while Al
and ZnO displayed little change. CeO
increased in zeta potential; however, the net
charge remained negative. Cytotoxicity studies revealed that TiO
and Fe
caused decreasing cellular viability over 48 h.
, ZnO, and CeO
cellular viability remained similar to control. Results indicate that alterations in the pH have a large
effect on zeta potential and agglomerate size which may be used as a predictive measure of nanotoxicity.
Keywords: Metal oxide nanoparticles,zeta potential,agglomeration,pH,cellular viability
Within the nanotoxicology eld, increased ndings
demonstrate the ability of nanoparticle charge (zeta
potential) to inuence corresponding cellular
responses ranging from particulate endocytosis to
cytotoxicity (Xia et al. 2006; Nan et al. 2008; Lundq-
vist et al. 2009). Reviews of current literature suggest
a need for careful characterization of all classes of
nanomaterials including metal colloids, metal oxides,
and carbonaceous particles, prior to their use in
toxicity testing (Karakoti et al. 2006; Handy
et al. 2008). The relationship between zeta potential
and ambient conditions surrounding the nanoparti-
cles remains a largely unexplored area which will
require researchers from many scientic disciplines
to answer. This research probes the effects of pH on
nanoparticle zeta potential and size using ~30 nm
particles in aqueous suspension. The nanoparticles
include titanium dioxide (TiO
), iron oxide (Fe
aluminum oxide (Al
), zinc oxide (ZnO), and
cerium dioxide (CeO
). In these nanoparticle
systems, which include both the nanoparticle and
the suspension medium, features such agglomeration,
dispersion, and suspension stability may be
inuenced by external factors such as the ux of
hydrogen ions (H+) in solution.
The zeta potential represents the charge of a nano-
particle in relation to the surrounding conditions.
Nevertheless, the zeta potential is not an actual mea-
surement of the individual molecular surface charge;
rather, it is a measurement of the electric double layer
produced by the surrounding ions in solution (i.e.,
counter ions) (Malvern Instruments 2008). These
counter ions play a role in the calculation of zeta
potential measurement (Figure 1). All particle systems
in an aqueous media carry an electric charge which
may be positive, negative, or neutral. For surface-
derived nanoparticles, dissociation of an acidic group,
such as a carboxylic acid moiety on a nanoparticle
surface will yield a negatively charged surface; while
dissociation of a basic group on a nanoparticle surface
will yield a positively charged surface. For unmodied
nanoparticles, the individual atoms that comprise the
surface of the particle dictate its charge.
Relevance to toxicology
Agglomeration of nanoparticles occurs when individ-
ual particles are held together by weak inter-particle
Correspondence: Christie M. Sayes, Department of Veterinary Physiology & Pharmacology, TAMU 4466, College Station, Texas 77843, USA. Tel: +1 979 862
2682. Fax: +1 979 862 4929. E-mail:
ISSN 1743-5390 print/ISSN 1743-5404 online 2009 Informa UK Ltd.
DOI: 10.3109/17435390903276941
interactions including solvation forces, van der Waals
forces, electrostatic attractions, and hydrophobic
interactions (Hakim et al. 2007; Fichthorn and
Qin 2008; Min et al. 2008). In most instances,
agglomeration state is reversible, but only if additional
entropy (e.g., sonication or homogenization) or ions
(changing H+) are added to the system. It is suspected
that this methodology could be used to size select for
certain nano-populations within a particle suspension.
Limitations of utilizing changes in pH for biological
applications are that the resultant suspension could
have a pH that is outside of the physiological range
(7.357.45), may alter chemistry of drug delivery
vehicles, or change conditions in cell culture media
for in vitro use (Klaassen and Watkins 2003). Further,
this methodology could yield insights into the fate and
transport of nanoparticle aggregates after an exposure
has occurred.
A likely exposure to nanoparticles may occur orally
(Gatti et al. 2009). This route of exposure would
ensure that nanoparticles enter an environment yield-
ing a wide range of pH values. Initially, the nanopar-
ticle would be exposed to a low pH in the stomach
(pH =~2) (Rodriguez et al. 1999; Beak et al. 2006).
Following acidic conditions in the stomach, the envi-
ronment is once again altered in the intestinal tract,
yielding a more basic pH combined with peristaltic
movement. Under these physiological situations,
physical properties of the agglomerates such as size,
surface area, and zeta potential will change. This
alteration in physical properties will yield nanoagglo-
merates of differing size and may increase likelihood
that these nanoparticles could translocate through the
endothelial lining and enter the circulatory system.
This in turn may induce a systemic and/or chronic
effect (Lockman et al. 2004; Oberdörster 2007;
Semmler-Behnke et al. 2007; Panessa-Warren
et al. 2008; Santhanam et al. 2008).
Altering the pH of the medium in which the nano-
particle is suspended will also yield differences in
nanoparticle dissolution into ions or alter the surface
chemistry of a nanoparticle (Guo et al. 2009). Altering
the surface chemistry of nanoparticles may in turn
effect how a nanoparticle binds cellular substituents
such as proteins, and may affect the mechanisms by
which these nanoparticles enter cells (Al-Jamal
et al. 2008; Lundqvist et al. 2009).
Discovering the fundamental relationships between
the properties of nanomaterials and certain toxicolog-
ical responses will require the separation of the com-
plex kinetics of nanoparticle delivery in vitro from the
dynamics of response. This could be made possible by
integrated computational and experimental dose-
response analyses.
Experimental procedures
Particle preparation
Titanium dioxide (TiO
,~27 nm, 99.8%) particles
were acquired from Evonik, Hanau-Wolfgang, Ger-
many. Aluminum oxide, zinc oxide, and cerium diox-
ide (Al
,<50 nm, 99.5%; ZnO, <50 nm, 99.5%;
,<25 nm, 99.5%) nanoparticles were purchased
from Sigma Aldrich, St Louis, Missouri, USA. Iron
oxide (Fe
,2335 nm, 98%) nanoparticles were
synthesized using a ame synthesis method that has
been described in detail elsewhere (Yang et al. 2001;
Guo and Kennedy 2007). The stock solutions of each
of the ve ~30 nm particles were prepared in Milli-Q
ultrapure water (18.2 mW). The resultant suspensions
Figure 1. Schematic diagram of the effects of pH on a metal oxide nanoparticle. The zeta potential plane is measured as the primary indicator
of surface charge. Surface charge is altered when the pH is increased or decreased. The downstream effect of altered zeta potential is a change in
agglomeration state, which inuences the cytotoxicity.
Nanoparticle pH, charge, toxicity 277
were bath sonicated for 30 min prior to material
characterization and in vitro exposures. Nanoparticle
size was visualized using dynamic light scattering
(DLS). Zeta potential was measured via electropho-
retic light scattering (ELS) combined with phase
analysis light scattering (PALS) (Malvern Zetasizer
Nano ZS). Size and zeta potential parameters were
measured over various time points ranging from
t=0 h to t =1 wk.
Nanoparticle titration was performed using the Mal-
vern MPT-2 Autotitrator in parallel with the Malvern
Zetasizer Nano-ZS. This combination allowed auto-
mated titration over a wide pH range and thus made it
possible to determine the isoelectric point (IEP).
Nanoparticles were titrated from basic pH
(pH =12) to an acidic pH (pH =2) utilizing HCl
and NaOH. At every pH unit (±0.2 U) the zeta
potential and size were determined. The IEP was
determined using the Malvern Software Version 5.03.
The concentration of the nanoparticles used was
dependent upon the turbidity of the sample. The zeta
potential and agglomerate size of ZnO, Al
were measured at a concentration of 200 ppm
(mg/l); TiO
was measured at a concentration of 50
ppm (mg/l); and Fe
was measured at a concentra-
tion of 25 ppm (mg/l). The differences in nanoparticle
concentration for IEP measurements were necessary
due to the refractive indices of the nanoparticles
probed; however, as a note, a higher concentration
of nanoparticles would facilitate increased incidence of
collision, thus leading to agglomeration when com-
pared to a lower concentration of nanoparticles.
Cytotoxicity studies were performed by dosing cul-
tured mouse hepatocytes (AML12, American Type
Tissue Collection, Manassas, VA, USA) with 10 mg/l
nanoparticles in 24-well plates. Dosed wells differed
only by the type of nanoparticles used and not the
concentration of nanoparticles. A control was added
for comparison. DMEM/F-12 media was used for all
cells. The dosed-cell plates were incubated at 37C.
Cell viability was determined using a Countess Auto-
mated Cell Counter (Invitrogen Corp., Carlsbad, CA,
USA) in combination with trypan blue dye at 1 h, 24
h, and 48-h post-exposure time points. Dead cells
exhibit a compromised membrane, which allows the
dye to penetrate, providing for differentiation from
live cells.
Results indicate that the pH has a pronounced effect on
the zeta potential of each nanoparticle tested in this
study. The change in zeta potential was found to alter
the stability of the nanoparticle suspension. Figure 2B
E illustrates the titration curves of TiO
. A hypothetical model nanoparticle
exhibits the largest agglomerate size at the point where
its zeta potential is 0 mV (Figure 2A), as was deter-
mined empirically for the remainder of the tested nano-
particles (Figure 2BE).Thepointatwhichthe
nanoparticle exhibits no net charge is termed the iso-
electric point (IEP). ZnO, Al
display an IEP (IEP =7.13, 7.06, and 6.71, respectively)
at a pH relevant to interstitial uid, broncheoalveloar
lavage uid, lymph, and blood (Klaassen and Wat-
kins 2003). However, this trend does not continue
for TiO
and Fe
nanoparticles. The TiO
nanoparticles exhibited an IEP at pH 5.19
and 4.24, respectively. The largest nanoparticle agglom-
erate size was dependent upon chemical composition
and ranged from 1,772 ±47.56 nm in the Fe
to 3,185 ±541.0 nm in the Al
suspension. Further-
more, the smallest agglomerate size throughout each
nanoparticle suspension existed at the pH where the
nanoparticle displayed a strongly charged surface. The
charge repulsions between the particles, thus maintain-
ing a more stable and monodisperse suspension. The
smallest nanoparticle size was found in the ZnO sample
(203.8 nm). This size is indicative of the hydrodynamic
radius of the nanoparticle.
In addition to changes in pH, the zeta potential of a
nanoparticle changes over time when held in aqueous
suspension. Figure 3 demonstrates that the nanopar-
ticles tested demonstrate a wide range of agglomera-
tion states and zeta potentials over a time period t =1h
to t =1 wk. Over the course of this experiment, TiO
and Fe
nanoparticles displayed a large zeta poten-
tial increase, which consequently affected their agglom-
eration state. TiO
and Fe
nanoparticles originally
exhibited zeta potentials of -29 mV and -32 mV
respectively; however, after the one-week time point,
the zeta potential rose to -15 mV. As witnessed in both
of these nanoparticles, a more neutral surface charge
led to larger agglomeration state. On the contrary, ZnO
and Al
nanoparticles retained their negative surface
charge over time. In these samples, stability was due to
the strongly negative-charged zeta potential and the
lack of agglomeration. CeO
nanoparticles demon-
strated a slight increase in zeta potential over the
one-week time course. Interestingly, this slight increase
still led to a very negative zeta potential of -27.8 mV.
Because the zeta potential remained close to -30 mV, a
278 J.M. Berg et al.
number commonly used to indicate solution stability,
the agglomeration state of the nanoparticles decreased
Cellular viability in the AML12 mouse liver hepa-
tocyte was examined at 24 and 48-h time points. It was
noted that while the TiO
- and Fe
-dosed samples
exhibited heightened cellular viability at the 1 h time
point, they showed a decrease in viability each time
thereafter. The ZnO and Al
samples displayed
increasing cell viability at 48 h, with viability of 91.5%
and 91.75%, respectively. This percentage is com-
pared to the control cell viability of 96.0% after 48 h.
Figure 2. Titration of nanoparticles in ultrapure water (18.2 mW). (A) In a model nanoparticle system, the largest aggregate size would be
observed at its isoelectric point (zeta potential =0 mV). The farther the zeta potential deviates from 0 mV, the smaller the particle agglomerate
due to increasing repulsive forces. Titrations of (B) TiO
, (C) ZnO, (D) Al
, (E) CeO
, and (F) Fe
from basic (pH >10) to acidic
(pH <3) conditions. All nanoparticles exhibit an isoelectric point (IEP). Results indiciate that zeta potential and size are dependent upon pH.
Dashed vertical line represents isoelectric point.
Nanoparticle pH, charge, toxicity 279
nanoparticles, which exhibited only a slight
change in cell viability, initially yielded 85.25% with a
nal 48 h post-exposure time point viability of 90%.
Results indicate that alterations in the pH have a large
effect on zeta potential and agglomerate size which
may be used a predictive measure of nanoparticle
toxicity. The suspension stability is dependent upon
physical characteristics of both the suspended nano-
particles and their suspension medium. One of the
major factors involved in the agglomeration process is
electrostatic stabilization. Altering the zeta potential
to the point at which it exhibits zero net charge, or the
IEP of the nanoparticle, decreases stabilization forces
and promotes agglomeration.
Figure 3. Alterations in zeta potential change over time. The zeta potential of various metal oxide nanoparticles were measured over a time
period of t =0tot=1 week. Here, the TiO
nanoparticles (A) and the Fe
nanoparticles (B) had an increasing zeta potential value (smaller
absolute value). This increasing zeta potential corresponds with an increase in aggregate size. Both the Al
nanoparticles (C) and the ZnO
nanoparticles (D) remained highly negative, thus their aggregate size remained the same or decreased. CeO
nanoparticles (E) tend to decrease
in size slowly over time despite the apparent small increase in zeta potential (smaller absolute value).
280 J.M. Berg et al.
In accordance with Figure 2, all of the nanoparticles
tested displayed unique isoelectric points. While the
ZnO, CeO
nanoparticles possessed IEP at
a physiologically-relevant pH, such as blood or inter-
stitial uid (pH =7.4), Fe
and TiO
possessed IEP at acidic conditions. Conversely, the
and TiO
nanoparticles exhibited a charged
surface at pH =7.4. This data, when compared with
the difference in cellular viability seen in Figure 4,
suggests that the presence of a charged surface on the
nanoparticle agglomerate at physiological pH of 7.4
may correlate with a decrease in cellular viability in
The study is pertinent due the possibility that many
environments present in the body such as gastric
secretions, urine, and lysosomal uid are known to
have a varying degree of pH which correlate with our
ndings regarding nanoparticle surface charge. Table I
shows the representative pH of various bodily com-
partments which the particle would potentially be
exposed to over the course of the pharmacodynamic
process. Specically, a pH of 2 present in the acidic
Figure 4. Cellular viability after nanoparticle exposure (10 mg/l). Cellular viability correlates with the nanoparticle aggregation trend. AML12
cells were analyzed for cellular viabiliy at times t =0tot=48 hours post exposure. Both the TiO
nanoparticles (A) and the Fe
(B) displayed a decrease in cell viability until the 48 hr timepoint. This contrasts the Al
(C) and the ZnO (D) nanoparticle data, which
implies that cell viability increases over time. CsO nanoparticles (E) displayed no signicant change in viability. Control cells increased in
cellular viability. *p<0.05 vs. 1 h post-exposure time point within the same graph.
Nanoparticle pH, charge, toxicity 281
gastric secretions from parietal cells, would likely alter
the agglomeration state of the nanoparticles which have
been examined in this study. Physiological conditions
such as these would yield the smallest nanoparticle
agglomerates seen by the body. In addition, for many
of the nanoparticles tested, a strongly positive zeta
potential may further yield electrostatic or covalent
interactions with cellular components such as DNA
or proteins as well as determine the specicrouteof
uptake into the cell (Dausend et al. 2008).
Table I indicates that agglomerate size varies sig-
nicantly, depending upon a variety of factors, includ-
ing both pH and nanoparticle chemical composition.
One possible condition not explored in this paper is
the inuence of ionic strength due to the addition
of Na
and Cl
ions introduced during the titration.
Increasing the ionic strength of the suspension
medium may lead to an altered agglomeration state
through possible charge shielding and condensation of
the charge at the electric double layer (Tiyaboonchai
and Limpeanchob 2007; Handy et al. 2008). This
often poses a challenge when working with a biocom-
patible suspension medium. In addition, a buffered
suspension medium (such as phosphate buffered
saline) inuences the particle agglomeration state
(Sager et al. 2007). While these agglomerate sizes
seen in the nanoparticle titration are representative
of what would be seen in an aqueous suspension, it is
important to note that both in vitro and in vivo con-
ditions contain biomaterial, such as proteins and/or
lipids that may coat the nanoparticle surface, altering
both the chemistry and agglomeration state. This
emerging hypothesis has proven valuable as shifts in
the zeta potential and the isoelectric point have been
reported after proteins adsorb onto the particle sur-
face (Cael et al. 2003; Xia et al. 2006). It has been
suggested that this protein adsorption is just as sig-
nicant to toxicology as the inherit physico-chemical
characteristics of the nanoparticles themselves
(Lundqvist et al. 2009). Even in an in vivo model,
specic nanoparticle-protein interactions will not only
inuence the agglomeration state of nanoparticles,
cells. Although many reports have cited interactions
at the nanomaterial-biological interface, these dyn-
amic properties are inuenced by the zeta potential
and agglomeration state. This research strives to
make a connection between these physico-chemical
characteristics as a predictive measure of nanoma-
terial toxicity.
Cellular viability was inuenced by a variety of
factors including zeta potential and agglomeration
state. Results indicate that, of the nanoparticles
tested, cellular exposure to Fe
and TiO
a decrease in viability over time. This alteration in
cellular viability correlates with the charged surface
and altered agglomeration state demonstrated by only
these nanoparticles. It is hypothesized that the poten-
tial toxicity of nanoparticles is due to not just one, but
many characteristics of the nanoparticle system. Our
data suggests that both pH and agglomeration state
show an association with cytotoxicity. Figure 3 shows
that these nanoparticles increase in agglomeration size
over time, coupled with a zeta potential trending
towards neutral. These experiments were carried
out in ultrapure water (pH =5.9). When suspended
in a solution where pH =7.4, as that which is seen in
cell culture media, Fe
and TiO
were the only
materials which were found not to be at or near their
IEP. These results indicate that surface charge has the
potential to inuence cell viability.
Overall, it is important that nanoparticles be clas-
sied as an entire system that encompasses the nano-
particle, its suspension medium, and the ions in
solution. This careful characterization is necessary
to interpret which components of a nanoparticle
may contribute to alterations in surface charge and
toxicological effects. We have shown that factors such
as pH can inuence the zeta potential of different
nanoparticles. Additionally, it was observed that
changes in zeta potential lead to a change in cellular
viability. In the future it will be important for research-
ers to carefully observe the conditions under which the
zeta potential is measured when reporting results.
Table I. Prediction of metal oxide nanomaterial properties in various pharmacodynamic compartments. The nanomaterials exhibit different zeta
potentials and agglomerate sizes at various physiological pH. TiO
and Fe
nanoparticles demonstrate strongly charged agglomerates at
pH =7.4. The pH values of 2.00, 4.50, 5.00, and 7.40 were chosen to represent various physiological matrices,such as gastric acid, lysosomal uid,
intestinal uid or urine, and blood or interstitial uid, respectively. Values are reported as zeta potential (mV) / average agglomerate size (nm).
Metal oxide nanomaterials <2.00 4.50 5.00 7.40
ZnO +50.0/360 +44.0/945 +16.0/1200 -3.00/1170
+45.0/561 +38.0/1750 +27.0/2400 -4.00/3050
+32.6/1440 +26.0/2340 +20.0/2590 -6.00/2850
+25.4/1800 -9.00/1740 -15.0/1700 -47.0/830
282 J.M. Berg et al.
The authors thank Dr Bing Guo of the Department of
Mechanical Engineering at Texas A&M University
for supplying the Fe
nanoparticle samples. We
also thank the Department of Veterinary Physiology
and Pharmacology for supporting this work.
Declaration of interest:The authors report no
conicts of interest. The authors alone are responsible
for the content and writing of the paper.
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Nanoparticle pH, charge, toxicity 283
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... The work of Berg et al. reveals that the isoelectric point for zinc oxide occurs at the pH value of 7.13; above this value, the charge present on the surface of the oxide is positive and is negative below it. Moreover, below pH 4 and above pH 8, ZnO nanoparticles form very electrokinetically stable dispersions (zeta potential value ±40 mV) [59]. ...
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In recent years, increasing attention has been paid to the durability of building materials, including those based on cementitious binders. Important aspects of durability include the increase of the strength of the cement matrix and enhancement of material resistance to external factors. The use of nanoadditives may be a way to meet these expectations. In the present study, zinc, titanium and copper oxides, used in single and binary systems (to better the effect of their performance), were applied as additives in cement mortars. In the first part of this work, an extensive physicochemical analysis of oxides was carried out, and in the second, their application ranges in cement mortars were determined. The subsequent analyses were employed in determining the physicochemical properties of pristine oxides: Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray fluorescence (EDXRF), scanning electron microscopy (SEM), measurement of the particle size distribution, as well as zeta potential measurement depending on the pH values. Influence on selected physicomechanical parameters of the cement matrix and resistance to the action of selected Gram-positive and Gram-negative bacteria and fungi were also examined. Our work indicated that all nanoadditives worsened the mechanical parameters of mortars during the first 3 days of hardening, while after 28 days, an improvement was achieved for zinc and titanium(IV) oxides. Binary systems and copper(II) oxide deteriorated in strength parameters throughout the test period. In contrast, copper(II) oxide showed the best antibacterial activity among all the tested oxide systems. Based on the inhibitory effect of the studied compounds, the following order of microbial susceptibility to inhibition of growth on cement mortars was established (from the most susceptible, to the most resistant): E. coli < S. aureus < C. albicans < B. cereus = P. aeruginosa < P. putida.
We created glassy carbon electrodes (GCEs) modified with CeO2 nanoparticles and various surfactants and determined the voltammetric characteristics of tartrazine oxidation on them. The electrode modified with the cationic surfactant cetyltriphenylphosphonium bromide (CTPPB) ensures a 72.5-fold increase in the oxidation currents of tartrazine compared to a GCE. The oxidation of tartrazine on the CeO2 -CTPPB/GCE proceeds irreversibly, involves one electron, and is controlled by surface processes. A procedure was developed for the voltammetric determination of tartrazine on a CeO2-CTPPB/GCE. The analytical range is 1.00–250 μM of tartrazine with a limit of detection of 0.4 μM. The procedure was applied to quantify tartrazine in the Tarkhun beverage.
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This study deals with heavy metal ions removal from simulated water using biosynthesized silica-supported iron oxide nanocomposites (nano-IOS). Agricultural and garden wastes have been utilized to prepare nano-IOS through a green synthesis process. Nano-IOS was characterized by XRD, SEM, FTIR, and zeta potential analysis. The nanocomposites were used to remove five heavy metals, viz., Pb²⁺, Cd²⁺, Ni²⁺, Cu²⁺, and Zn²⁺, with optimization of reaction parameters including pH, the concentration of heavy metals, adsorbent dosage, and contact time in batch mode experiments. The optimized dose of nano-IOS was 0.75 g/L for the adsorption of Pb²⁺, Cd²⁺, Ni²⁺, Cu²⁺, and Zn²⁺ (10.0 mg/L) with a contact duration of 70 min at pH 5.0 for Pb²⁺, Cd²⁺, and Cu²⁺ and 6.0 for Ni²⁺ and Zn²⁺. The adsorption behavior of the nano-adsorbent was well described by Langmuir adsorption isotherm and pseudo-second-order kinetic model indicating chemisorption on the surface of nano-IOS. The adsorption was also found spontaneous and endothermic. Thus, the environmentally benign and bio-synthesized nano-IOS can be utilized as an effective nano-adsorbent for the rapid sequestration of heavy metal ions from water and wastewater.
Objective: Rosuvastatin (ROS) is a class of antihyperlipidemic agents belonging to the class of statins with poor permeability, which results in low oral bioavailability, i.e. 20%. The objective of the present study was to improve the permeability and bioavailability of ROS by developing nanocochelates using naturally biocompatible phosphatidylcholine, a type of lipid which is used as Ca 2+ cations for the calcification process. Significance: For the loaded ROS, the trapping method was used to build nanocochelates to boost the intestinal permeability of phosphatidylcholine and divalent choline is a calcium chloride cationic solution. Methods: Nine different formulations have been produced and with varying lipid and cationic solution concentrations. The formulation of nanocochelates characterized by scanning electron microscopy, particle size, and zeta potential. Permeability studies have been conducted to determine the permeability improvement property of nanocochelates. The pharmacokinetic study was performed in Wistar albino rats to determine the bioavailability enhancement potential of nanocochlelates. Results: The concentration of optimum lipid, calcium chloride was found to be 80 mg, 200 ul respectively which improve permeability by 3.44 times as compared to the marketed formulation. The in-vitro drug release over a prolonged period i.e.12 hours. Which was substantially better than the traditional formulation of tablets. Nearly five fold enhancement in bioavailability was observed in case of optimized formulation as compared to the marketed formulation (p < 0.05). Conclusion: The findings suggest that the use of natural lipid carrier by nanocochelates of Rosuvastatin was promising the oral delivery approach.
Excess amount of amoxicillin in food products endangers the health of consumers, and, therefore, requires effective control measures. In this paper, the factors that affect selection and effectivity of the quantitative analysis of amoxicillin were investigated using SERS method. It was demonstrated that under silver nanoparticles controlled agglomeration conditions in the presence of calcium chloride and under the specific pH value, the enhancement factor (EF) reached 8.1×10⁷, which was 10000 times greater than what was observed under uncontrolled conditions. Depending on the pH value, the study of structural changes happening on the surface of silver nanoparticles in amoxicillin was conducted. Based on the resulted patterns and on the chemometric analysis (PLS), an ultrasensitive method for quantitative measurement of amoxicillin was developed in the concentration range of 25-1000 nmol/L with high correlation coefficient (R² = 0.9988) and with the limit of detection 0.44 nmol/L.
The paper presents the positive effect of soybean polypeptides (SP) on the stability and the potential hypolipidemic effect of selenium nanoparticles (SeNPs). After preparing SeNPs, SP with different molecular weight were introduced to stabilize SeNPs. We found that the SP with molecular weight >10 kDa (SP5) had the best stabilizing effect on SeNPs. We inferred that the steric resistance resulting from the long chains of SP5 protected SeNPs from collision-mediated aggregation, and the electrostatic repulsions between SP5 and SeNPs also played a positive role in stabilizing SeNPs. The as-prepared SP5-SeNPs were spherical, amorphous and zero valent. It was proved that SeNPs were bound with SP5 through O- and N- groups in SP5, and the main forces were hydrogen bonds and van der Waals forces. The bile salts binding assay showed that the SP5-SeNPs exhibited a high binding capacity to bile salts, which indicated their potential in hypolipidemic application.
Background: Submicron particles (SMPs), as novel bionanomaterials, offer complementary benefits to their conventional nano-counterparts. Aim: To explore zinc oxide (ZnO) SMPs' bio-imaging and anticancer potentials. Materials & methods: ZnO SMPs were synthesized into two shapes. Fluorescent spectrum and microscopy were studied for the bioimaging property. Wound healing and Live/Dead assays of glioblastoma cells were characterized for anticancer activities. Results: ZnO SMPs exhibited a high quantum yield (49%) with stable orange fluorescence emission. Both morphologies (most significant in the rod shape) showed tumor-selective properties in cytotoxicity, inhibition to cell migration and attenuating the cancer-upregulated genes. The tumor selectivity was attributed to particle degradation and surface properties on pH dependency. Conclusion: The authors propose that ZnO SMPs could be a promising anticancer drug with tunable, morphology-dependent properties for bioimaging and controlled release.
This article covers a simple one-step method that has been developed for ion-induced activation/agglomeration of silver nanoparticles. While using this method in Surface-enhanced Raman spectroscopy (SERS) we have recorded high values of signal enhancement factor (EF= 3.9×10⁶). An important feature of the method is high stability of analytical signal (RSD of about 2% with analyte concentration at 1 ppb). We have shown, that in case of activation of nanoparticles with chlorides of alkaline earth metals the signal amplification proceeds according to a different mechanism rather than in case of NaCl. It was found that the synergistic action of two-charged cations (Ca²⁺, Mg²⁺, Ba²⁺) and chloride ions leads to the agglomeration of silver nanoparticles and the formation of “hot spots”, whereas in the case of NaCl at a concentration of up to 1 mM, only the surface modification of Ag NPs occurs. Kinetic studies have been carried out, and the mechanism of this process has been proposed. The obtained data served as a basis for the development of a simple and sensitive express method for the determination of trace amounts (in the range of 0.1-10 ppb, LOD = 0.002 ppb) of malachite green in water from natural sources. In order to compensate matrix effects we applied a standard addition method which simplified considerably the sample preparation process, increased method’s accuracy and reduced the time of analysis.
In this study, two novel polyurea thin film composite (TFC) nanofiltration membranes were prepared by interfacial polymerization. Chitosan (CS) and piperazine (PIP) were interfacially polymerized by toluene diisocyanate (TDI) monomer on the surface of poly(acrylonitrile) (PAN) support layer. Surface morphology of TFC nanofiltration membranes was evaluated by field emission-scanning electron microscopy (FE-SEM) and atomic force microscopy (AFM). In addition, surface charge, contact angle, pure water flux, and mebeverine hydrochloride rejection were performed. FE-SEM images confirmed formation of thin film and a dense top layer on the membrane surface. AFM images showed higher average roughness for TFC-PIP, in comparison with TFC-CS1.5 and PAN substrate. Flux decreased from 18 to 15 L/m2h, while mebeverine hydrochloride rejection increased from 63% for TFC-PIP to 95% for TFC-CS1.5. In addition, the fouling parameters showed better antifouling behavior of TFC-CS1.5 membrane, i.e. flux recovery ratio (FRR): 95.3% and total fouling ratio (Rt): 33.3%. Finally, TFC-CS1.5 membrane was considered as an optimum membrane with the best performance and minimum fouling.
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The past 20 years have witnessed simultaneous multidisciplinary explosions in experimental techniques for synthesizing new materials, measuring and manipulating nanoscale structures, understanding biological processes at the nanoscale, and carrying out large-scale computations of many-atom and complex macromolecular systems. These advances have led to the new disciplines of nanoscience and nanoengineering. For reasons that are discussed here, most nanoparticles do not 'self-assemble' into their thermodynamically lowest energy state, and require an input of energy or external forces to 'direct' them into particular structures or assemblies. We discuss why and how a combination of self- and directed-assembly processes, involving interparticle and externally applied forces, can be applied to produce desired nanostructured materials. © 2010 Nature Publishing Group, a division of Macmillan Publishers Limited and published by World Scientific Publishing Co. under licence. All Rights Reserved.
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A diffusion flame system was used to generate an aerosol of soot and iron oxide. The primary fuel was ethylene. Iron was introduced by passing ethylene over liquid iron pentacarbonyl. The aerosol emission from the flame was diluted by secondary air to a level that could be used in animal exposure studies. The system was designed to operate at a constant soot production rate while the iron loading was varied from 0 to 50 g m-3 in the diluted postflame gases. The impact of the iron on soot production was counteracted by the addition of acetylene to the fuel. Particles were collected on carbon grids and were examined via transmission electron microscopy. Electron energy loss spectroscopy was employed to characterize the aerosol. A differential mobility analyzer was used to measure the size distribution of the aerosol. The iron particles were typically 40 nm in diameter and often appeared in isolation from the soot aerosol, suggesting that either they were not formed concurrently with the soot or they remained after oxidation of the surrounding soot. Samples collected from within the flame, and downstream of the flame, indicated that the iron may have been present as very small particles comingled with the soot. The iron particles apparently melted and coalesced as they passed through the high temperature flame tip. Crystallization of the iron proceeded as the postflame gases cooled by mixing with external air. The flame system was shown to be capable of consistently producing steady concentrations of soot and iron for delivery to animals, without the confounding presence of toxic gaseous compounds.
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Iron oxide nanoparticles, to be used in a health effects study, were synthesized in a H2/air diffusion flame and characterized by transmission electron microscopy, X-ray diffraction, surface area measurement, inductively coupled plasma mass spectrometry, and a spectrophotometric speciation method. The nanoparticles exhibited the maghemite (γ -Fe2O3) crystal structure and contained only trivalent iron. There were two size modes in the particles. The large size mode contained crystalline, non-agglomerated particles with a median diameter of approximately 45 nm; the small size mode contained particles that were in the size range of 3–8 nm and were mostly amorphous. Depending on the value taken for the small particle size, the small mode accounted for 73–82% of the particle surface area. The particles in the small size mode were likely formed from the vapor of FeO and Fe.
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The past 20 years have witnessed simultaneous multidisciplinary explosions in experimental techniques for synthesizing new materials, measuring and manipulating nanoscale structures, understanding biological processes at the nanoscale, and carrying out large-scale computations of many-atom and complex macromolecular systems. These advances have led to the new disciplines of nanoscience and nanoengineering. For reasons that are discussed here, most nanoparticles do not 'self-assemble' into their thermodynamically lowest energy state, and require an input of energy or external forces to 'direct' them into particular structures or assemblies. We discuss why and how a combination of self- and directed-assembly processes, involving interparticle and externally applied forces, can be applied to produce desired nanostructured materials.
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Nanoparticles agglomerate and clump in solution, making it difficult to accurately deliver them for in vivo or in vitro experiments. Thus, experiments were conducted to determine the best method to suspend nanosized particles. Ultrafine and fine carbon black and titanium dioxide were suspended in phosphate buffered saline (PBS), rat and mouse bronchoalveolar lavage fluid (BALF), and PBS containing dipalmitoyl phosphatidylcholine (DPPC) and/or mouse serum albumin. To assess and compare how these various suspension media dispersed the nanoparticles, images were taken using light microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The results of this study show that PBS is not a satisfactory medium to prepare nanoparticle suspensions. However, BALF was an excellent media in which to suspend nanoparticles. The use of PBS containing protein or DPPC alone, in concentrations found in BALF, did not result in satisfactory particle dispersion. However, PBS-containing protein plus DPPC was satisfactory, although less effective than BALF.
Market: pharmacy students; occupational medicine clinicians; undergraduate and graduate pharmacology/toxicology students; public health students; undergraduate environmental science; poison control centres Sales Handle The most concise entry-level textbook to the science and clinical field of medical toxicology. Replete with useful pedagogical features and learning aids, and written at a level suitable for students just beginning their studies in toxicology. Now with end-of-chapter self-assessment Q&A, and now in full colour! About the book Essentials of Toxicology is an entry-level distillation of the field's gold-standard text Casarett and Doull's Toxicology. It combines an accessible and engaging approach with coverage of essential introductory concepts to provide the beginning student with a solid grounding in basic and medical toxicology. The Second Edition features a new full-colour format and a wealth of new pedagogical features and learning aids to make understanding faster and easier than ever.
Functionalized-quantum-dot-liposome (f-QD-L) hybrid nanoparticles are engineered by encapsulating poly(ethylene glycol)-coated QD in the internal aqueous phase of different lipid bilayer vesicles. f-QD-L maintain the QD fluorescence characteristics as confirmed by fluorescence spectroscopy, agarose gel electrophoresis, and confocal laser scanning microscopy. Cationic f-QD-L hybrids lead to dramatic improvements in cellular binding and internalization in tumor-cell monolayer cultures. Deeper penetration into three-dimensional multicellular spheroids is obtained for f-QD-L by modifying the lipid bilayer characteristics of the hybrid system. f-QD-L are injected intratumorally into solid tumor models leading to extensive fluorescent staining of tumor cells compared to injections of the f-QD alone. f-QD-L hybrid nanoparticles constitute a versatile tool for very efficient labeling of cells ex vivo and in vivo, particularly when long-term imaging and tracking of cells is sought. Moreover, f-QD-L offer many opportunities for the development of combinatory therapeutic and imaging (theranostic) modalities by incorporating both drug molecules and QD within the different compartments of a single vesicle
This paper describes some early cellular and intracellular interactions of human polarised lung and colon epithelial cells (representative of two portals of entry, inhalation and ingestion), following exposure to specific carbon and gold engineered nanoparticles in vitro. Cells were incubated with functionalised and non-functionalised carbon nanotube-derived nanoloops (∼28–60 nm diameter), or gold nanoparticles (2 nm and 10 nm Au-core) which were either non-functionalised, or functionalised with biological proteins or ssDNA and analysed using viability staining, transmission electron microscopy (TEM) and field emission scanning (FESEM) electron microscopy. Even with such diverse nanoparticles and functionalisations, we found that the surface properties and size of the nanoparticles determined their cellular binding, incorporation and/or cytotoxicity. However the cells responded to the different types of nanoparticles using various intracellular routes which differed with the cell type, but all of the nanoparticles ultimately were consolidated into aggregates and transported to the basal cell surface. Nanoparticles that were completely covered with biological macromolecules (i.e., recombinant gClq-R protein, non-immune IgGk, monoclonal antibody to gClq-R, or ssDNA) did not cause ultrastructural damage or changes in the cell monolayers. Monoclonal antibody (mAb)-functionalised carbon nanoloops and ssDNA 100% covered Au-nanodots were incorporated and transported within the colon cells using different cellular pathways than those used by the lung cells. Citrate-capped Au-nanoparticles (2 nm and 10 nm) and 20% DNA covered Au-nanoparticles passed into the colon and lung cells through small holes in the apical cell membrane, which could possibly be produced by lipid peroxidation. Serious forms of cell damage were observed with citrate capped 2 nm and 10 nm Au-nanoparticles (i.e., nuclear localisation (2 nm-Au); intracellular membrane damage (10 nm-Au)). Vital staining used to identify cellular necrosis following nanoparticle exposure, was sometimes misleading showing cell necrosis statistics similar to normal controls, when TEM analysis revealed intracellular and organellar damage in identically treated cells.
The nose can be an efficient filter for inhaled gases, vapours and particles that may be harmful to the lung. Nasal airways may also be targets for injury caused by inhaled toxicants. To investigate the nasal toxicity of carbon black nanoparticles (CB), rats were exposed to 0, 1, 7 or 50 mg/m³ of high surface area CB (HSCB; primary particle size 17 nm; particle surface area 300 m²/g) for 6 h/day, 5 days/week for 13 week. Additional rats were exposed to 50 mg/m³ of low surface area CB (LSCB; primary particle size 70 nm; particle surface area 37 m²/g). Rats were sacrificed 1 day, 13 week, or 11 months postexposure (PE). Rats exposed to mid- or high-dose HSCB had nasal inflammatory and epithelial lesions at one day PE. HSCB-induced nasal inflammation resolved by 13 week PE, but some nasal epithelial lesions were still present in rats at 11 months after high-dose HSCB exposure. Low-dose HSCB or high-dose LSCB induced only minimal epithelial lesions that were resolved by 13 week PE. Results indicate that incidence, severity, and persistence of CB-induced nasal toxicity in rats is dependent on exposure concentration, particle surface area, and time PE. Effects of inhaled CB on human nasal airways are yet to be determined.
Serious pathologies have been linked recently to aluminum toxicity. In this study, model mono- and bilayers were used to get more insight into the interactions of aluminum with phospholipid membranes. To establish if lipid membranes differentiate between cations of a similar electron structure and to determine thermodynamic parameters of Al3+ complexation, both aluminum and praseodymium salts were used. An NMR investigation using phosphatidylcholine unilamellar liposomes in the presence of Al(III) and Pr(III) was performed in order to obtain information on the structure and stability of the complexes formed between the metal cations and the phosphate heads of the lipids. The Langmuir film technique was used to study the influence of Al(III) and Pr(III) on phosphatidylcholine monolayers spread at the air/water interface. Surface pressure and surface potential measurements allowed us to monitor the organization of the lipid molecules and the film property changes. Important differences were observed in the effect induced in the model membranes by the two metal cations. On the other hand, it became obvious that the role of the anion has to be taken into account when rationalizing the interactions of the metal cation with lipid membranes.