scholarly journals A New Bevacizumab Carrier for Intravitreal Administration: Focus on Stability

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 560
Author(s):  
Daniela Chirio ◽  
Elena Peira ◽  
Simona Sapino ◽  
Giulia Chindamo ◽  
Simonetta Oliaro-Bosso ◽  
...  

Bevacizumab (BVZ) is a monoclonal antibody that binds to human vascular endothelial growth factor A (VEGF-A) and inhibits the interaction between VEGF-A and VEGF receptors, thus blocking the angiogenesis. Repeated intravitreal injections of BVZ for the treatment of ocular pathologies that present an excessive proliferation results in a low patience compliance. BVZ is specially indicated for the treatment of diabetic and degenerative retinopathy. In the present study, we designed lipid nanoparticles (NPs) as a BVZ sustained drug delivery system for reducing the frequency of administration. We used a simple and highly efficient procedure, “Cold dilution of microemulsions”, to obtain spherical NPs with mean diameters of 280–430 nm, Zeta potentials between −17 and −31 mV, and drug entrapment efficiencies between 50 to 90%. This study focused on the biochemical and biophysical stabilities of BVZ after entrapment in NPs. SDS-PAGE electrophoretic analysis and circular dichroism, dynamic light scattering, and scanning electron microscopy were used to characterize BVZ-loaded NPs. The biocompatibility was assessed by in vitro cell compatibility studies using the ARPE-19 cell line. Thus, in this work, a stable BVZ-loaded system was obtained. In addition, several studies have shown that BVZ is released slowly from the lipid matrix and that this system is biocompatible. The results are promising and the developed NPs could be exploited to create a new, potentially effective and minimally invasive treatment of intraocular diseases.

1999 ◽  
Vol 599 ◽  
Author(s):  
William L. Murphy ◽  
Katherine A. Gilhool ◽  
David H. Kohn ◽  
David J. Mooney

AbstractBasic design requirements of scaffolds for bone tissue engineering applications include biocompatibility, temporally controlled degradability, osteoconductivity, mechanical integrity, and mass transport capabilities. A recent study has attempted to meet design criteria via the growth of a carbonated apatite (bone-like) mineral on the inner pore surfaces of a highly porous 85:15 poly(lactide-co-glycolide) scaffold using a biomimetic process. It has also been recently demonstrated that the mineralization strategy can be combined with sustained growth factor delivery to induce vascular tissue ingrowth. The present study examines the effect of protein presence on the mineralization process by measuring the amount of protein incorporated into the scaffold during the process of mineral formation. Surprisingly, vascular endothelial growth factor incorporates more readily into control scaffolds than into scaffolds subjected to mineralization treatment. This finding suggests that there is little incorporation of protein into the growing mineral film, and offers insight into the mechanism for sustained drug delivery from the mineralized scaffolds.


Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4127
Author(s):  
Aline de Cristo Soares Alves ◽  
Franciele Aline Bruinsmann ◽  
Silvia Stanisçuaski Guterres ◽  
Adriana Raffin Pohlmann

Bevacizumab (BCZ) is a recombinant humanized monoclonal antibody against the vascular endothelial growth factor, which is involved in the angiogenesis process. Pathologic angiogenesis is observed in several diseases including ophthalmic disorders and cancer. The multiple administrations of BCZ can cause adverse effects. In this way, the development of controlled release systems for BCZ delivery can promote the modification of drug pharmacokinetics and, consequently, decrease the dose, toxicity, and cost due to improved efficacy. This review highlights BCZ formulated in organic nanoparticles providing an overview of the physicochemical characterization and in vitro and in vivo biological evaluations. Moreover, the main advantages and limitations of the different approaches are discussed. Despite difficulties in working with antibodies, those nanocarriers provided advantages in BCZ protection against degradation guaranteeing bioactivity maintenance.


Author(s):  
Kamil Wartalski ◽  
Gabriela Gorczyca ◽  
Jerzy Wiater ◽  
Zbigniew Tabarowski ◽  
Małgorzata Duda

AbstractEndothelial cells (ECs), the primary component of the vasculature, play a crucial role in neovascularization. However, the number of endogenous ECs is inadequate for both experimental purposes and clinical applications. Porcine ovarian putative stem cells (poPSCs), although not pluripotent, are characterized by great plasticity. Therefore, this study aimed to investigate whether poPSCs have the potential to differentiate into cells of endothelial lineage. poPSCs were immunomagnetically isolated from postnatal pig ovaries based on the presence of SSEA-4 protein. Expression of mesenchymal stem cells (MSCs) markers after pre-culture, both at the level of mRNA: ITGB1, THY, and ENG and corresponding protein: CD29, CD90, and CD105 were significantly higher compared to the control ovarian cortex cells. To differentiate poPSCs into ECs, inducing medium containing vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF), epidermal growth factor (EGF), ascorbic acid, and heparin was applied. After 14 days, poPSC differentiation into ECs was confirmed by immunofluorescence staining for vascular endothelial cadherin (VECad) and vascular endothelial growth factor receptor-2 (VEGFR-2). Semi-quantitative WB analysis of these proteins confirmed their high abundance. Additionally, qRT-PCR showed that mRNA expression of corresponding marker genes: CDH5, KDR was significantly higher compared with undifferentiated poPSCs. Finally, EC functional status was confirmed by the migration test that revealed that they were capable of positive chemotaxis, while tube formation assay demonstrated their ability to develop capillary networks. In conclusion, our results provided evidence that poPSCs may constitute the MSC population in the ovary and confirmed that they might be a potential source of ECs for tissue engineering.


Neuroreport ◽  
2006 ◽  
Vol 17 (13) ◽  
pp. 1369-1373 ◽  
Author(s):  
Juergen-Theodor Fraenzer ◽  
Frank-Peter Wachs ◽  
Otto Gleich ◽  
Anna-Katharina Licht ◽  
J??rgen Strutz

Vox Sanguinis ◽  
2001 ◽  
Vol 80 (3) ◽  
pp. 170-178 ◽  
Author(s):  
H. J. Nielsen ◽  
K. Werther ◽  
T. Mynster ◽  
M. N. Svendsen ◽  
S. Rosendahl ◽  
...  

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