scholarly journals SYNTHESIS, CHARACTERIZATION, AND IN VIVO IMMUNOMODULATION OF CCR2 AND VASCULAR ENDOTHELIAL GROWTH FACTOR ANTAGONISTS-LOADED PEGYLATED NANOPARTICLES

2019 ◽  
Vol 12 (1) ◽  
pp. 275
Author(s):  
Ahmed A Abd-rabou ◽  
Hanaa H Ahmed ◽  
Mohamed S Kishta
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Concentration Ratio ◽  
Immune Cell ◽  
Drug Clearance ◽  
Vascular Endothelial ◽  
Pegylated Nanoparticles ◽  
Endothelial Growth Factor ◽  
Ccr2 Antagonist

Objective: Chemokine (C-C motif) ligand 2 (CCL2), a candidate of cytokines, orchestrates immune cell recruitment to inflamed organs. CCL2 has been shown to have direct angiogenic effects, so providing an anti-angiogenic agent, Avastin (AV), to be combined with the CCR2 antagonist (concentration ratio [CR]) plays an essential role in the hemostatic strategy for immunomodulation. Lack of targetability and the adverse effects of chemical treatments are the main obstacles led scientists to develop novel strategies using nano-delivery approaches such as pegylated nanoparticles (NPs) which exhibits reduced drug clearance rates. The rationale of the current study is to test the in vivo immunomodulatory effects of AV and/or CR in their NPs or free counterparts.Methods: These NPs were synthesized and characterized using different physicochemical techniques. Males Wistar rats (n=114) were used and divided into 7 groups treated with vehicle, AV, AVNP, CCR2 antagonist (CR), CCR2 antagonist NPs (CRNP), AV-CCR2 antagonist (AVCR), and AV-CCR2 antagonist NPs (AVCRNP). Groups were subdivided into three subgroups according to the administrated dose. Blood was taken from rats for differential leukocyte and platelet profile measurements. Sera were collected to test vascular endothelial growth factor (VEGF) levels. Autopsy samples from liver were taken for histopathological investigation.Results: The morphology of the NPs was spherical and had sizes ranging from 89.89 nm to 146 nm. Monocytes and lymphocytes accumulated in the blood circulation and VEGF levels were inhibited after AV and CR administrations. In addition, large platelets concentration ratio was elevated in the blood circulation.Conclusion: We concluded that AV ad CR therapeutic regimens have an immunomodulatory role through induction of monocyte-platelet aggregation and inhibition of VEGF.

scholarly journals SYNTHESIS, CHARACTERIZATION, AND IN VIVO IMMUNOMODULATION OF CCR2 AND VASCULAR ENDOTHELIAL GROWTH FACTOR ANTAGONISTS-LOADED PEGYLATED NANOPARTICLES

2019 ◽  
Vol 12 (1) ◽  
pp. 275
Author(s):  
Ahmed A Abd-rabou ◽  
Hanaa H Ahmed ◽  
Mohamed S Kishta
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Concentration Ratio ◽  
Immune Cell ◽  
Drug Clearance ◽  
Vascular Endothelial ◽  
Pegylated Nanoparticles ◽  
Endothelial Growth Factor ◽  
Ccr2 Antagonist

Objective: Chemokine (C-C motif) ligand 2 (CCL2), a candidate of cytokines, orchestrates immune cell recruitment to inflamed organs. CCL2 has been shown to have direct angiogenic effects, so providing an anti-angiogenic agent, Avastin (AV), to be combined with the CCR2 antagonist (concentration ratio [CR]) plays an essential role in the hemostatic strategy for immunomodulation. Lack of targetability and the adverse effects of chemical treatments are the main obstacles led scientists to develop novel strategies using nano-delivery approaches such as pegylated nanoparticles (NPs) which exhibits reduced drug clearance rates. The rationale of the current study is to test the in vivo immunomodulatory effects of AV and/or CR in their NPs or free counterparts.Methods: These NPs were synthesized and characterized using different physicochemical techniques. Males Wistar rats (n=114) were used and divided into 7 groups treated with vehicle, AV, AVNP, CCR2 antagonist (CR), CCR2 antagonist NPs (CRNP), AV-CCR2 antagonist (AVCR), and AV-CCR2 antagonist NPs (AVCRNP). Groups were subdivided into three subgroups according to the administrated dose. Blood was taken from rats for differential leukocyte and platelet profile measurements. Sera were collected to test vascular endothelial growth factor (VEGF) levels. Autopsy samples from liver were taken for histopathological investigation.Results: The morphology of the NPs was spherical and had sizes ranging from 89.89 nm to 146 nm. Monocytes and lymphocytes accumulated in the blood circulation and VEGF levels were inhibited after AV and CR administrations. In addition, large platelets concentration ratio was elevated in the blood circulation.Conclusion: We concluded that AV ad CR therapeutic regimens have an immunomodulatory role through induction of monocyte-platelet aggregation and inhibition of VEGF.

scholarly journals Role of vascular endothelial growth factor in inducing production of angiopoetin-1 – in vivo study in Fisher rats

2017 ◽  
Vol 68 (4) ◽  
pp. 326-329
Author(s):  
Piotr Barć ◽  
Tomasz Płonek ◽  
Dagmara Baczyńska ◽  
Artur Pupka ◽  
Wojciech Witkiewicz ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
In Vivo Study ◽  
Vascular Endothelial ◽  
Angiopoetin 1 ◽  
Endothelial Growth Factor

Mice overexpressing placenta growth factor exhibit increased vascularization and vessel permeability

2002 ◽  
Vol 115 (12) ◽  
pp. 2559-2567 ◽  
Author(s):  
Teresa Odorisio ◽  
Cataldo Schietroma ◽  
M. Letizia Zaccaria ◽  
Francesca Cianfarani ◽  
Cecilia Tiveron ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Adult Life ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Placenta Growth Factor ◽  
Vessel Permeability ◽  
Exact Function ◽  
Endothelial Growth Factor

Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family, comprising at least five cytokines specifically involved in the regulation of vascular and/or lymphatic endothelium differentiation. Several lines of evidence indicate a role for PlGF in monocyte chemotaxis and in potentiating the activity of VEGF, but the exact function of this cytokine is not fully understood. To define the biological role of PlGF in vivo, we have produced a transgenic mouse model overexpressing this factor in the skin by using a keratin 14 promoter cassette. Our data indicate that PlGF has strong angiogenic properties in both fetal and adult life. PlGF overexpression results in a substantial increase in the number,branching and size of dermal blood vessels as well as in enhanced vascular permeability. Indeed, intradermally injected recombinant PlGF was able to induce vessel permeability in wild-type mice. The analysis of vascular endothelial growth factor receptor 1/flt-1 and vascular endothelial growth factor receptor 2/flk-1 indicates that the two receptors are induced in the skin endothelium of transgenic mice suggesting that both are involved in mediating the effect of overexpressed PlGF.

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