Synergistic Antitumor Potency of a Self-Assembling Peptide Hydrogel for the Local Co-delivery of Doxorubicin and Curcumin in the Treatment of Head and Neck Cancer.

Combination therapy has been conferred with manifold assets leveraging the synergy of different agents to achieve a sufficient therapeutic outcome with lower administered drug doses and reduced side effects. The therapeutic potency of a self-assembling peptide hydrogel for the co-delivery of doxorubicin and curcumin was assessed against head and neck cancer cells. The dual loaded peptide hydrogel enabled control over the rate of drug release based on drug's aqueous solubility. A significantly enhanced cell growth inhibitory effect was observed after treatment with the combination drug-loaded hydrogel formulations compared to the respective combination drug solution. The synergistic pharmacological effect of selected hydrogel formulations was further confirmed with enhanced apoptotic cell response, interference in cell cycle progression, and significantly altered apoptotic/anti-apoptotic gene expression profiles obtained in dose levels well below the half-maximal inhibitory concentrations of both drugs. The in vivo antitumor efficacy of the drug-loaded peptide hydrogel formulation was confirmed in HSC-3 cell-xenografted severe combined immunodeficient mice and visualized with µCT imaging. Histological and terminal deoxynucleotidyl transferase dUTP nick end labeling assay analyses of major organs were implemented to assess the safety of the topically administered hydrogel formulation. Overall, results demonstrated the therapeutic utility of the dual drug-loaded peptide hydrogel as a pertinent approach for the local treatment of head and neck cancer.

Canagliflozin-loaded magnetic nanoparticles as potential treatment of hypoxic tumors in combination with radiotherapy.

AIM: To synthesize magnetic nanoparticles loaded with the SGLT2-inhibitor canagliflozin (CANA) and evaluate its anticancer potential under normoxic and hypoxic conditions in combination or not with radiotherapy. MATERIAL & METHODS: Iron oxide nanoparticles were synthesized via an alkaline hydrolytic precipitation of iron precursor in the presence of poly(methacrylic acid)-graft-poly(ethyleneglycol methacrylate). CANA was conjugated to the nanoparticles using N-ethyl-N'-(3-dimethyl aminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide chemistry. The anticancer efficacy of the nanoparticles was evaluated in cancer cell lines and in a mouse PDV C57 tumor model. RESULTS: In the mouse xenograft cancer model, the combination of CANA-loaded nanoparticles with radiotherapy (in the presence of an external magnetic field at the tumor site) exhibited higher antitumor activity compared with the combination of free CANA with radiotherapy. CONCLUSION: The results obtained indicate the potential that the combination of selective delivery of a SGLT2 inhibitor such as CANA with radiotherapy holds as an anticancer treatment.

Silibinin Improves TNF-α and M30 Expression and Histological Parameters in Rat Kidneys After Hepatic Ischemia/Reperfusion.

BACKGROUND: Remote kidney damage is a sequel of hepatic ischemia-reperfusion (I/R) injury. Silibinin is the main ingredient of the milk thistle plant seed extract with known antioxidant and hepatoprotective activity. Our study investigates the nephroprotective potential of intravenously administered silibinin, as a lyophilized SLB-hydoxypropyl-beta-cyclodextrin product, in hepatic I/R injury. MATERIAL AND METHODS: 63 Wistar rats were divided into three groups: Sham (virtual intervention); Control (45 min ischemia and reperfusion); and Silibinin (200 µL intravenous silibinin administration after 45 min of ischemia). Kidney tissues were collected to determine TNF-α, M30 and histopathological changes at predetermined time intervals. RESULTS: Comparing Sham vs. Control groups, proved that hepatic I/R injury increased renal TNF-α and M30 expression. Deterioration was observed in hyperemia/filtration of renal parenchyma and tubules, cortical filtration, tubular necrosis and edema (tissue swelling index). Intravenous silibinin administration and comparison of the Control vs. Silibinin groups showed a statistically significant decrease in TNF-α levels at 240 min following I/R (p < 0.0001), and in M30 at 180 min (p = 0.03) and 240 min (p < 0.0001). Renal parameters have significantly decreased in: hyperemia/filtration of renal parenchyma at 120 min (p = 0.003), 180 min (p = 0.0001) and 240 min (p = 0.0002); hyperemia/filtration of renal tubules at 120 min (p = 0.02), 180 min (p = 0.0001) and 240 min (p = 0.0005); cortical filtration (240 min - p = 0.005); tubular necrosis (240 min - p = 0.021); and edema (240 min - p = 0.001). CONCLUSION: Our study confirms that hepatic I/R injury causes remote renal damage while the intravenous administration of silibinin leads to statistically significant nephroprotective action.

Assessing the exploratory and anxiety-related behaviors of mice. Do different caging systems affect the outcome of behavioral tests?

Ample studies have shown that housing can affect the health, welfare and behavior of mice and therefore, the outcomes of certain experiments. The aim of this study was to investigate if three widely used housing systems, Open Top Cages (OTC), Motor Free Ventilated Cages (MFVC) and Individually Ventilated Cages (IVC) may affect exploratory and anxiety-related behaviors in mice. Subjects were 8week-old male C57Bl/6J mice (n=36) divided into three groups, OTC, IVC and MFVC groups, respectively. The experimental procedure consisted of two behavioral tests: the open field and the elevated plus maze test. Although there were no differences in the open field test, the results from the elevated plus maze showed that animals housed in the MFVCs exhibited increased exploratory and less anxiety-like behavior. It is concluded that the different caging systems may have an impact on the outcome of behavioral tests used to assess exploratory and anxiety like behavior in mice. Therefore, it is essential to take into consideration housing conditions when reporting, analyzing, and/or systematically reviewing the results of behavioral testing in mice.

Effects of using the analgesic tramadol in mice undergoing embryo transfer surgery.

Embryo transfer is a surgical technique that is widely used in reproductive biotechnology. Despite the ethical obligation to relieve animals' post-operative pain, analgesia is not routinely provided after embryo transfer surgery because it has been suggested that analgesics may be detrimental to embryo survival. Studies suggest, however, that the potential for adverse effects varies depending on the type of analgesic used and the timing of its administration. The authors carried out a study to determine whether pre-operatively administered tramadol, a synthetic analogue of codeine, influenced birth rate, litter survival or the post-operative body weights of surrogate dams. Compared with controls that were not given any analgesic, surrogate dams given tramadol had similar birth rates and similar body weights at all time points. The tramadol-treated surrogate dams showed a statistically significant increase in the number of offspring that survived to weaning. The authors conclude that pre-operatively administered tramadol does not harm the success rate of embryo transfer surgery and even may improve litter survival.