13 research outputs found
Additional file 2 of Population pharmacokinetic analysis of lopinavir in HIV negative individuals exposed to SARS-CoV-2: a COPEP (COronavirus Post-Exposure Prophylaxis) sub-study
Additional file 2: Figure S1. Observed plasma concentrations of LPV for the two study populations. Figure S2. Distribution of ka estimated by bootstrap. Table S1. PK parameters of the published popPK models
Additional file 1 of Population pharmacokinetic analysis of lopinavir in HIV negative individuals exposed to SARS-CoV-2: a COPEP (COronavirus Post-Exposure Prophylaxis) sub-study
Additional file 1. Dataset analyzed during this study
C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes
Poly(2-methyl-2-oxazoline) (PMOXA)
is an alternative promising polymer to poly(ethylene glycol) (PEG)
for design and engineering of macrophage-evading nanoparticles (NPs).
Although PMOXA-engineered NPs have shown comparable pharmacokinetics
and <i>in vivo</i> performance to PEGylated stealth NPs
in the murine model, its interaction with elements of the human innate
immune system has not been studied. From a translational angle, we
studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived
organically modified silica NPs (PMOXA-coated NPs) of approximately
100 nm in diameter with human complement system, blood leukocytes,
and macrophages and compared their performance with PEGylated and
uncoated NP counterparts. Through detailed immunological and proteomic
profiling, we show that PMOXA-coated NPs extensively trigger complement
activation in human sera exclusively through the classical pathway.
Complement activation is initiated by the sensing molecule C1q, where
C1q binds with high affinity (<i>K</i><sub>d</sub> = 11
± 1 nM) to NP surfaces independent of immunoglobulin binding.
C1q-mediated complement activation accelerates PMOXA opsonization
with the third complement protein (C3) through the amplification loop
of the alternative pathway. This promoted NP recognition by human
blood leukocytes and monocyte-derived macrophages. The macrophage
capture of PMOXA-coated NPs correlates with sera donor variability
in complement activation and opsonization but not with other major
corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps
C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes
Poly(2-methyl-2-oxazoline) (PMOXA)
is an alternative promising polymer to poly(ethylene glycol) (PEG)
for design and engineering of macrophage-evading nanoparticles (NPs).
Although PMOXA-engineered NPs have shown comparable pharmacokinetics
and <i>in vivo</i> performance to PEGylated stealth NPs
in the murine model, its interaction with elements of the human innate
immune system has not been studied. From a translational angle, we
studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived
organically modified silica NPs (PMOXA-coated NPs) of approximately
100 nm in diameter with human complement system, blood leukocytes,
and macrophages and compared their performance with PEGylated and
uncoated NP counterparts. Through detailed immunological and proteomic
profiling, we show that PMOXA-coated NPs extensively trigger complement
activation in human sera exclusively through the classical pathway.
Complement activation is initiated by the sensing molecule C1q, where
C1q binds with high affinity (<i>K</i><sub>d</sub> = 11
± 1 nM) to NP surfaces independent of immunoglobulin binding.
C1q-mediated complement activation accelerates PMOXA opsonization
with the third complement protein (C3) through the amplification loop
of the alternative pathway. This promoted NP recognition by human
blood leukocytes and monocyte-derived macrophages. The macrophage
capture of PMOXA-coated NPs correlates with sera donor variability
in complement activation and opsonization but not with other major
corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps
C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes
Poly(2-methyl-2-oxazoline) (PMOXA)
is an alternative promising polymer to poly(ethylene glycol) (PEG)
for design and engineering of macrophage-evading nanoparticles (NPs).
Although PMOXA-engineered NPs have shown comparable pharmacokinetics
and <i>in vivo</i> performance to PEGylated stealth NPs
in the murine model, its interaction with elements of the human innate
immune system has not been studied. From a translational angle, we
studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived
organically modified silica NPs (PMOXA-coated NPs) of approximately
100 nm in diameter with human complement system, blood leukocytes,
and macrophages and compared their performance with PEGylated and
uncoated NP counterparts. Through detailed immunological and proteomic
profiling, we show that PMOXA-coated NPs extensively trigger complement
activation in human sera exclusively through the classical pathway.
Complement activation is initiated by the sensing molecule C1q, where
C1q binds with high affinity (<i>K</i><sub>d</sub> = 11
± 1 nM) to NP surfaces independent of immunoglobulin binding.
C1q-mediated complement activation accelerates PMOXA opsonization
with the third complement protein (C3) through the amplification loop
of the alternative pathway. This promoted NP recognition by human
blood leukocytes and monocyte-derived macrophages. The macrophage
capture of PMOXA-coated NPs correlates with sera donor variability
in complement activation and opsonization but not with other major
corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps
C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes
Poly(2-methyl-2-oxazoline) (PMOXA)
is an alternative promising polymer to poly(ethylene glycol) (PEG)
for design and engineering of macrophage-evading nanoparticles (NPs).
Although PMOXA-engineered NPs have shown comparable pharmacokinetics
and <i>in vivo</i> performance to PEGylated stealth NPs
in the murine model, its interaction with elements of the human innate
immune system has not been studied. From a translational angle, we
studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived
organically modified silica NPs (PMOXA-coated NPs) of approximately
100 nm in diameter with human complement system, blood leukocytes,
and macrophages and compared their performance with PEGylated and
uncoated NP counterparts. Through detailed immunological and proteomic
profiling, we show that PMOXA-coated NPs extensively trigger complement
activation in human sera exclusively through the classical pathway.
Complement activation is initiated by the sensing molecule C1q, where
C1q binds with high affinity (<i>K</i><sub>d</sub> = 11
± 1 nM) to NP surfaces independent of immunoglobulin binding.
C1q-mediated complement activation accelerates PMOXA opsonization
with the third complement protein (C3) through the amplification loop
of the alternative pathway. This promoted NP recognition by human
blood leukocytes and monocyte-derived macrophages. The macrophage
capture of PMOXA-coated NPs correlates with sera donor variability
in complement activation and opsonization but not with other major
corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps
C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes
Poly(2-methyl-2-oxazoline) (PMOXA)
is an alternative promising polymer to poly(ethylene glycol) (PEG)
for design and engineering of macrophage-evading nanoparticles (NPs).
Although PMOXA-engineered NPs have shown comparable pharmacokinetics
and <i>in vivo</i> performance to PEGylated stealth NPs
in the murine model, its interaction with elements of the human innate
immune system has not been studied. From a translational angle, we
studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived
organically modified silica NPs (PMOXA-coated NPs) of approximately
100 nm in diameter with human complement system, blood leukocytes,
and macrophages and compared their performance with PEGylated and
uncoated NP counterparts. Through detailed immunological and proteomic
profiling, we show that PMOXA-coated NPs extensively trigger complement
activation in human sera exclusively through the classical pathway.
Complement activation is initiated by the sensing molecule C1q, where
C1q binds with high affinity (<i>K</i><sub>d</sub> = 11
± 1 nM) to NP surfaces independent of immunoglobulin binding.
C1q-mediated complement activation accelerates PMOXA opsonization
with the third complement protein (C3) through the amplification loop
of the alternative pathway. This promoted NP recognition by human
blood leukocytes and monocyte-derived macrophages. The macrophage
capture of PMOXA-coated NPs correlates with sera donor variability
in complement activation and opsonization but not with other major
corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps
C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes
Poly(2-methyl-2-oxazoline) (PMOXA)
is an alternative promising polymer to poly(ethylene glycol) (PEG)
for design and engineering of macrophage-evading nanoparticles (NPs).
Although PMOXA-engineered NPs have shown comparable pharmacokinetics
and <i>in vivo</i> performance to PEGylated stealth NPs
in the murine model, its interaction with elements of the human innate
immune system has not been studied. From a translational angle, we
studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived
organically modified silica NPs (PMOXA-coated NPs) of approximately
100 nm in diameter with human complement system, blood leukocytes,
and macrophages and compared their performance with PEGylated and
uncoated NP counterparts. Through detailed immunological and proteomic
profiling, we show that PMOXA-coated NPs extensively trigger complement
activation in human sera exclusively through the classical pathway.
Complement activation is initiated by the sensing molecule C1q, where
C1q binds with high affinity (<i>K</i><sub>d</sub> = 11
± 1 nM) to NP surfaces independent of immunoglobulin binding.
C1q-mediated complement activation accelerates PMOXA opsonization
with the third complement protein (C3) through the amplification loop
of the alternative pathway. This promoted NP recognition by human
blood leukocytes and monocyte-derived macrophages. The macrophage
capture of PMOXA-coated NPs correlates with sera donor variability
in complement activation and opsonization but not with other major
corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps
C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes
Poly(2-methyl-2-oxazoline) (PMOXA)
is an alternative promising polymer to poly(ethylene glycol) (PEG)
for design and engineering of macrophage-evading nanoparticles (NPs).
Although PMOXA-engineered NPs have shown comparable pharmacokinetics
and <i>in vivo</i> performance to PEGylated stealth NPs
in the murine model, its interaction with elements of the human innate
immune system has not been studied. From a translational angle, we
studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived
organically modified silica NPs (PMOXA-coated NPs) of approximately
100 nm in diameter with human complement system, blood leukocytes,
and macrophages and compared their performance with PEGylated and
uncoated NP counterparts. Through detailed immunological and proteomic
profiling, we show that PMOXA-coated NPs extensively trigger complement
activation in human sera exclusively through the classical pathway.
Complement activation is initiated by the sensing molecule C1q, where
C1q binds with high affinity (<i>K</i><sub>d</sub> = 11
± 1 nM) to NP surfaces independent of immunoglobulin binding.
C1q-mediated complement activation accelerates PMOXA opsonization
with the third complement protein (C3) through the amplification loop
of the alternative pathway. This promoted NP recognition by human
blood leukocytes and monocyte-derived macrophages. The macrophage
capture of PMOXA-coated NPs correlates with sera donor variability
in complement activation and opsonization but not with other major
corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps
C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes
Poly(2-methyl-2-oxazoline) (PMOXA)
is an alternative promising polymer to poly(ethylene glycol) (PEG)
for design and engineering of macrophage-evading nanoparticles (NPs).
Although PMOXA-engineered NPs have shown comparable pharmacokinetics
and <i>in vivo</i> performance to PEGylated stealth NPs
in the murine model, its interaction with elements of the human innate
immune system has not been studied. From a translational angle, we
studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived
organically modified silica NPs (PMOXA-coated NPs) of approximately
100 nm in diameter with human complement system, blood leukocytes,
and macrophages and compared their performance with PEGylated and
uncoated NP counterparts. Through detailed immunological and proteomic
profiling, we show that PMOXA-coated NPs extensively trigger complement
activation in human sera exclusively through the classical pathway.
Complement activation is initiated by the sensing molecule C1q, where
C1q binds with high affinity (<i>K</i><sub>d</sub> = 11
± 1 nM) to NP surfaces independent of immunoglobulin binding.
C1q-mediated complement activation accelerates PMOXA opsonization
with the third complement protein (C3) through the amplification loop
of the alternative pathway. This promoted NP recognition by human
blood leukocytes and monocyte-derived macrophages. The macrophage
capture of PMOXA-coated NPs correlates with sera donor variability
in complement activation and opsonization but not with other major
corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps