Formulation and Characterization of Nanosized Ethosomal Formulations of Antigout Model Drug (Febuxostat) Prepared by Cold Method: In Vitro/Ex Vivo and In Vivo Assessment

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Ahmed A. El-Shenawy ◽  
Wael A. Abdelhafez ◽  
Ahmed Ismail ◽  
Alaa A. Kassem
2015 ◽  
Vol 1 (1) ◽  
pp. 236-239 ◽  
Author(s):  
Sandra Stein ◽  
Christian Simroth-Loch ◽  
Sönke Langner ◽  
Stefan Hadlich ◽  
Oliver Stachs ◽  
...  

AbstractThe in vitro and in vivo characterization of intravitreal injections plays an important role in developing innovative therapy approaches. Using the established vitreous model (VM) and eye movement system (EyeMoS) the distribution of contrast agents with different molecular weight was studied in vitro. The impact of the simulated age-related vitreal liquefaction (VL) on drug distribution in VM was examined either with injection through the gel phase or through the liquid phase. For comparison the distribution was studied ex vivo in the porcine vitreous. The studies were performed in a magnetic resonance (MR) scanner. As expected, with increasing molecular weight the diffusion velocity and the visual distribution of the injected substances decreased. Similar drug distribution was observed in VM and in porcine eye. VL causes enhanced convective flow and faster distribution in VM. Confirming the importance of the injection technique in progress of VL, injection through gelatinous phase caused faster distribution into peripheral regions of the VM than following injection through liquefied phase. VM and MR scanner in combination present a new approach for the in vitro characterization of drug release and distribution of intravitreal dosage forms.


2016 ◽  
Vol 511 (2) ◽  
pp. 719-727 ◽  
Author(s):  
Cristina Cañadas ◽  
Helen Alvarado ◽  
Ana C. Calpena ◽  
Amélia M. Silva ◽  
Eliana B. Souto ◽  
...  

Nanomaterials ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3152
Author(s):  
Afrah Nawaz ◽  
Syed Mohsin Ali ◽  
Nosheen Fatima Rana ◽  
Tahreem Tanweer ◽  
Amna Batool ◽  
...  

Metallic nanoparticles, such as gold nanoparticles (AuNPs), have been extensively studied as drug delivery systems for various therapeutic applications. However, drug-loaded-AuNPs have been rarely explored in vivo for their effect on bacteria residing inside tissues. Ciprofloxacin (CIP) is a second-generation fluoroquinolone with a broad-spectrum of antibiotic properties devoid of developing bacteria resistance. This research is focused on the synthesis and physical characterization of Ciprofloxacin-loaded gold nanoparticles (CIP-AuNPs) and their effect on the colonization of Enterococcus faecalis in the liver and kidneys of mice. The successfully prepared CIP-AuNPs were stable and exerted enhanced in vitro antibacterial activity against E. faecalis compared with free CIP. The optimized CIP-AuNPs were administered (500 µg/Kg) once a day via tail vein to infected mice for eight days and were found to be effective in eradicating E. faecalis from the host tissues. Moreover, unlike CIP, CIP-AuNPs were non-hemolytic. In summary, this study demonstrated that CIP-AuNPs are promising and biocompatible alternative therapeutics for E.-faecalis-induced infections resistant to conventional drugs (e.g., beta-lactams and vancomycin) and should be further investigated.


1999 ◽  
Author(s):  
Diane L. Hern-Anderson ◽  
Anne Marie J. Hernandez ◽  
John P. Ranieri ◽  
Steven Weinberg

Abstract Many have hypothesized that both chemical and mechanical material properties are important in the design of a small bore vascular graft. In an attempt to address both issues, a xenogeneic graft crosslinked by photo-oxidation and covalently modified with heparin was developed. The compliance, burst strength, and suture pull strength of photo-oxidized (PhotoFix®) and heparin-modified photo-oxidized ovine carotid tissue were tested in vitro. The heparin modification process was found to have no statistically significant effect on any of these properties. The shrink temperature of fresh, photo-oxidized, and heparin-modified photo-oxidized tissue was assessed using DSC. A small increase in the shrink temperature of the heparin-modified photo-oxidized tissue over the fresh tissue was found to be statistically significant (P < 0.05). In vivo assessment of unmodified, heparin-soaked, and heparin-modified PhotoFix ovine grafts indicated that covalent modification of the grafts was imperative for the graft’s success.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Sebastián Ezequiel Pérez ◽  
Yamila Gándola ◽  
Adriana Mónica Carlucci ◽  
Lorena González ◽  
Daniel Turyn ◽  
...  

The aim of the present work was to take advantage of lecithin’s biocompatibility along with its physicochemical properties for the preparation of lecithin-based nanocarriers for small interfering RNA (siRNA) delivery. Water lecithin dispersions were prepared in different conditions, loaded with siRNA at different N/P ratios, and evaluated for loading capacity. The most appropriate ones were then assayed for cytotoxicity and characterized in terms of particle size distribution, zeta potential, and morphology. Results demonstrated that formulations prepared at pH 5.0 and 7.0 were able to load siRNA at broad N/P ratios, and cellular uptake assays showed an efficient delivery of oligos in MCF-7 human breast cancer cells; fluorescent-labeled dsRNA mainly located next to its target, near the nucleus of the cells. No signs of toxicity were observed for broad compositions of lecithin. The physicochemical characterization of the siRNA-loaded dispersions exhibited particles of nanometric sizes and pH-dependant shapes, which make them suitable for ex vivo and in vivo further evaluation.


Blood ◽  
2011 ◽  
Vol 118 (8) ◽  
pp. 2105-2115 ◽  
Author(s):  
Elisa Ciraci ◽  
Silvia Della Bella ◽  
Ombretta Salvucci ◽  
Cristina Rofani ◽  
Marta Segarra ◽  
...  

Abstract A precise identification of adult human hemangioblast is still lacking. To identify circulating precursors having the developmental potential of the hemangioblast, we established a new ex vivo long-term culture model supporting the differentiation of both hematopoietic and endothelial cell lineages. We identified from peripheral blood a population lacking the expression of CD34, lineage markers, CD45 and CD133 (CD34−Lin−CD45−CD133− cells), endowed with the ability to differentiate after a 6-week culture into both hematopoietic and endothelial lineages. The bilineage potential of CD34−Lin−CD45−CD133− cells was determined at the single-cell level in vitro and was confirmed by transplantation into NOD/SCID mice. In vivo, CD34−Lin−CD45−CD133− cells showed the ability to reconstitute hematopoietic tissue and to generate functional endothelial cells that contribute to new vessel formation during tumor angiogenesis. Molecular characterization of CD34−Lin−CD45−CD133− cells unveiled a stem cell profile compatible with both hematopoietic and endothelial potentials, characterized by the expression of c-Kit and CXCR4 as well as EphB4, EphB2, and ephrinB2. Further molecular and functional characterization of CD34−Lin−CD45−CD133− cells will help dissect their physiologic role in blood and blood vessel maintenance and repair in adult life.


2021 ◽  
Vol 13 (602) ◽  
pp. eaba4627
Author(s):  
Stelios Chrysostomou ◽  
Rajat Roy ◽  
Filippo Prischi ◽  
Lucksamon Thamlikitkul ◽  
Kathryn L. Chapman ◽  
...  

Lung and bladder cancers are mostly incurable because of the early development of drug resistance and metastatic dissemination. Hence, improved therapies that tackle these two processes are urgently needed to improve clinical outcome. We have identified RSK4 as a promoter of drug resistance and metastasis in lung and bladder cancer cells. Silencing this kinase, through either RNA interference or CRISPR, sensitized tumor cells to chemotherapy and hindered metastasis in vitro and in vivo in a tail vein injection model. Drug screening revealed several floxacin antibiotics as potent RSK4 activation inhibitors, and trovafloxacin reproduced all effects of RSK4 silencing in vitro and in/ex vivo using lung cancer xenograft and genetically engineered mouse models and bladder tumor explants. Through x-ray structure determination and Markov transient and Deuterium exchange analyses, we identified the allosteric binding site and revealed how this compound blocks RSK4 kinase activation through binding to an allosteric site and mimicking a kinase autoinhibitory mechanism involving the RSK4’s hydrophobic motif. Last, we show that patients undergoing chemotherapy and adhering to prophylactic levofloxacin in the large placebo-controlled randomized phase 3 SIGNIFICANT trial had significantly increased (P = 0.048) long-term overall survival times. Hence, we suggest that RSK4 inhibition may represent an effective therapeutic strategy for treating lung and bladder cancer.


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