Characterization and restoration of degenerated IVD function with an injectable, in situ gelling alginate hydrogel: An in vitro and ex vivo study

Author(s):  
Emily A. Growney Kalaf ◽  
Meghana Pendyala ◽  
J. Gary Bledsoe ◽  
Scott A. Sell
2018 ◽  
Vol 8 (3) ◽  
pp. 820-829 ◽  
Author(s):  
Manisha Sharma ◽  
Kaushik Chandramouli ◽  
Louise Curley ◽  
Beau Pontre ◽  
Keryn Reilly ◽  
...  

2016 ◽  
Vol 16 (12) ◽  
pp. 1615-1621 ◽  
Author(s):  
Erik Andrade-Jorge ◽  
Marycarmen Godínez-Victoria ◽  
Luvia Enid Sánchez-Torres ◽  
Luis Humberto Fabila-Castillo ◽  
José G. Trujillo-Ferrara

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Elodie A. Pérès ◽  
Jérôme Toutain ◽  
Louis-Paul Paty ◽  
Didier Divoux ◽  
Méziane Ibazizène ◽  
...  

Abstract Background Diacetyl-bis(N4-methylthiosemicarbazone), labeled with 64Cu (64Cu-ATSM) has been suggested as a promising tracer for imaging hypoxia. However, various controversial studies highlighted potential pitfalls that may disable its use as a selective hypoxic marker. They also highlighted that the results may be tumor location dependent. Here, we first analyzed uptake of Cu-ATSM and its less lipophilic counterpart Cu-Cl2 in the tumor over time in an orthotopic glioblastoma model. An in vitro study was also conducted to investigate the hypoxia-dependent copper uptake in tumor cells. We then further performed a comprehensive ex vivo study to compare 64Cu uptake to hypoxic markers, specific cellular reactions, and also transporter expression. Methods μPET was performed 14 days (18F-FMISO), 15 days (64Cu-ATSM and 64Cu-Cl2), and 16 days (64Cu-ATSM and 64Cu-Cl2) after C6 cell inoculation. Thereafter, the brains were withdrawn for further autoradiography and immunohistochemistry. C6 cells were also grown in hypoxic workstation to analyze cellular uptake of Cu complexes in different oxygen levels. Results In vivo results showed that Cu-ASTM and Cu-Cl2 accumulated in hypoxic areas of the tumors. Cu-ATSM also stained, to a lesser extent, non-hypoxic regions, such as regions of astrogliosis, with high expression of copper transporters and in particular DMT-1 and CTR1, and also characterized by the expression of elevated astrogliosis. In vitro results show that 64Cu-ATSM showed an increase in the uptake only in severe hypoxia at 0.5 and 0.2% of oxygen while for 64Cu-Cl2, the cell retention was significantly increased at 5% and 1% of oxygen with no significant rise at lower oxygen percentages. Conclusion In the present study, we show that Cu-complexes undoubtedly accumulate in hypoxic areas of the tumors. This uptake may be the reflection of a direct dependency to a redox metabolism and also a reflection of hypoxic-induced overexpression of transporters. We also show that Cu-ATSM also stained non-hypoxic regions such as astrogliosis.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shahar Cohen ◽  
Shirly Partouche ◽  
Michael Gurevich ◽  
Vladimir Tennak ◽  
Vadym Mezhybovsky ◽  
...  

AbstractWhole organ perfusion decellularization has been proposed as a promising method to generate non-immunogenic organs from allogeneic and xenogeneic donors. However, the ability to recellularize organ scaffolds with multiple patient-specific cells in a spatially controlled manner remains challenging. Here, we propose that replacing donor endothelial cells alone, while keeping the rest of the organ viable and functional, is more technically feasible, and may offer a significant shortcut in the efforts to engineer transplantable organs. Vascular decellularization was achieved ex vivo, under controlled machine perfusion conditions, in various rat and porcine organs, including the kidneys, liver, lungs, heart, aorta, hind limbs, and pancreas. In addition, vascular decellularization of selected organs was performed in situ, within the donor body, achieving better control over the perfusion process. Human placenta-derived endothelial progenitor cells (EPCs) were used as immunologically-acceptable human cells to repopulate the luminal surface of de-endothelialized aorta (in vitro), kidneys, lungs and hind limbs (ex vivo). This study provides evidence that artificially generating vascular chimerism is feasible and could potentially pave the way for crossing the immunological barrier to xenotransplantation, as well as reducing the immunological burden of allogeneic grafts.


INDIAN DRUGS ◽  
2016 ◽  
Vol 53 (01) ◽  
pp. 25-31
Author(s):  
M Priyanka ◽  
◽  
F. S. Dasankoppa ◽  
H. N Sholapur ◽  
NGN Swamy ◽  
...  

The poor bioavailability and the therapeutic effectiveness exhibited by the anti-depressant venlafaxine hydrochloride on oral administration is overcome by the use of ion-activated gel forming systems that are instilled as drops; these undergo gelation in the nasal cavity. The present study describes the design, characterization and evaluation of mucoadhesive nasal in situ gelling drug delivery of venlafaxine hydrochloride using different polymers like sodium alginate, HPMC and pectin in various concentrations. DSC studies revealed compatibility of the drug and excipients used. The in situ gels were characterized for physicochemical parameters, gelling ability, rheological studies, drug content, drug entrapment efficiency, in vitro mucoadhesive strength, water holding capacity, gel expansion coefficient and in vitro drug release studies. The amount of polymer blends was optimized using 23 full factorial design. The influence of experimental factors on percentage cumulative drug release at the end of 2 and 8 hours were investigated to get optimized formulation. The responses were analyzed using ANOVA and polynomial equation was generated for each response using multiple linear regression analysis. Optimized formulation, F9, containing 1.98% w/V sodium alginate, 0.64% w/V hydroxylpropyl methylcellulose, 0.99% w/V pectin showed percentage cumulative drug release of 19.33 and 80.44 at the end of 2 and 8 hours, respectively, which were close to the predicted values. The optimized formulation was subjected to stability study for three months at 300C /75% RH. The stability study revealed no significant change in pH, drug content and viscosity. Thus, venlafaxine hydrochloride nasal mucoadhesive in situ gel could be successfully formulated to improve bioavailability and to target the brain.


INDIAN DRUGS ◽  
2015 ◽  
Vol 52 (12) ◽  
pp. 23-33
Author(s):  
R. Kanekar ◽  
◽  
P. M. Dandagi ◽  
A. P. Gadad

The objective of the present study was to prepare and evaluate fast-dissolving oral films of prochlorperazine maleate (PCM), in order to enhance the bioavailability of the drug and to provide rapid onset of action thereby improving patient compliance. The solubility of the drug was increased by preparing inclusion complex with 2-hydroxypropyl-β-cyclodextrin (2HPβCD) and then incorporating it into the fast dissolving films. The fast-dissolving films of PCM were prepared by solvent casting method using different film forming polymers such as HPMC E15 and HPMC E5, either as single polymer or combination of the two. The film formulations were evaluated for various physico-chemical parameters. All formulations released more than 85% of the drug within 15 minutes. Formulation F4 showed best in vitro drug release profile. From the ex vivo study it was found that 94.79% of drug permeated through the porcine oral mucosa from the optimized formulation F4 within 60 mins.


2018 ◽  
Vol 68 (16) ◽  
pp. 965-977 ◽  
Author(s):  
Hossein Kamali ◽  
Elham Khodaverdi ◽  
Farzin Hadizadeh ◽  
Seyed Ahmad Mohajeri ◽  
Younes Kamali ◽  
...  

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