Biodegradable and biocompatible subcutaneous implants consisted of pH-sensitive mebendazole-loaded/folic acid-targeted chitosan nanoparticles for murine triple-negative breast cancer treatment

Journal of Nanobiotechnology, Journal Year: 2022, Volume and Issue: 20(1)

Published: March 31, 2022

Mebendazole (MBZ) is a well-known anti-parasite drug with significant anti-cancer properties. However, MBZ exhibits low solubility, limited absorption efficacy, extensive first-pass effect, and bioavailability. Therefore, multiple oral administration of high dose required daily for achieving the therapeutic serum level which can cause severe side effects patients' non-compliance.In present study, MBZ-loaded/folic acid-targeted chitosan nanoparticles (CS-FA-MBZ) were synthesized, characterized, used to form cylindrical subcutaneous implants 4T1 triple-negative breast tumor (TNBC) treatment in BALB/c mice. The efficacy CS-FA-MBZ was investigated after implantation comparison Control, (40 mg/kg, administration, twice week 2 weeks), CS-FA implants, according tumors' growth progression, metastasis, tumor-bearing mice survival time. Also, their biocompatibility evaluated by blood biochemical analyzes histopathological investigation vital organs.The completely degraded 15 days caused about 73.3%, 49.2%, 57.4% decrease mean volume Control (1050.5 ± 120.7 mm3), (552.4 76.1 (658.3 88.1 mm3) groups, respectively. Average liver metastatic colonies' number per microscope field at group (2.3 0.7) significantly (P < 0.05) lower than (9.6 1.7), (5.0 1.5), (5.2 1) groups. In addition, treated exhibited 52.1%, 27.3%, 17% more cancer cells injection MBZ, Moreover, biocompatible based on histopathology analyzes.Taking together, biodegradable murine TNBC model.

Language: Английский

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Cancer Metabolism as a Therapeutic Target and Review of Interventions

Nutrients, Journal Year: 2023, Volume and Issue: 15(19), P. 4245 - 4245

Published: Oct. 1, 2023

Cancer is amenable to low-cost treatments, given that it has a significant metabolic component, which can be affected through diet and lifestyle change at minimal cost. The Warburg hypothesis states cancer cells have an altered cell metabolism towards anaerobic glycolysis. Given this reprogramming in cells, possible target cancers metabolically by depriving them of glucose. In addition dietary modifications work on tumors metabolically, there are panoply nutritional supplements repurposed drugs associated with prevention better treatment outcomes. These interventions their evidentiary basis covered the latter half review guide future treatment.

Language: Английский

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Assessment of Drug-Induced Liver Injury through Cell Morphology and Gene Expression Analysis

Chemical Research in Toxicology, Journal Year: 2023, Volume and Issue: 36(9), P. 1456 - 1470

Published: Aug. 31, 2023

Drug-induced liver injury (DILI) is a significant concern in drug development, often leading to withdrawal. Although many studies aim identify biomarkers and gene/pathway signatures related toxicity predict DILI compounds, this remains challenge discovery. With strong development of high-content screening/imaging (HCS/HCI) for phenotypic screening, we explored the morphological cell perturbations induced by compounds. In first step, were associated with two datasets chemicals (DILIRank eTox). The mechanisms action then analyzed having transcriptomics data sharing similar perturbations. Signaling pathways (cell cycle, growth, apoptosis, ...) captured, hypothetical relation between gene deregulation was illustrated within our analysis. Finally, using signatures, machine learning approaches developed potential risk DILI. Some models showed relevant performance validation set balanced accuracies 0.645 0.739. Overall, findings demonstrate utility combining HCI expression chemicals. Moreover, protocol could be extended other end points, offering promising avenue comprehensive assessment

Language: Английский

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The Benzimidazole-Based Anthelmintic Parbendazole: A Repurposed Drug Candidate That Synergizes with Gemcitabine in Pancreatic Cancer

Cancers, Journal Year: 2019, Volume and Issue: 11(12), P. 2042 - 2042

Published: Dec. 17, 2019

Pancreatic cancer (PC) is one of the most lethal, chemoresistant malignancies and it paramount importance to find more effective therapeutic agents. Repurposing non-anticancer drugs may expand repertoire molecules. Studies on repurposing benzimidazole-based anthelmintics in PC their interaction with agents approved for therapy are lacking. We analyzed effects four Food Drug Administration (FDA)-approved benzimidazoles AsPC-1 Capan-2 pancreatic cell line viability. Notably, parbendazole was potent benzimidazole affecting viability, half maximal inhibitory concentration (IC50) values nanomolar range. The drug markedly inhibited proliferation, clonogenicity migration lines through mechanisms involving alteration microtubule organization formation irregular mitotic spindles. Moreover, interfered cycle progression promoting G2/M arrest, followed by emergence enlarged, polyploid cells. These abnormalities, suggesting a catastrophe, culminated apoptosis, also associated DNA damage lines. Remarkably, combinations gemcitabine, employed as first-line treatment PC, synergistically decreased In conclusion, this first study providing evidence that single agent, or combination candidate currently dismal therapy.

Language: Английский

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Potential and mechanism of mebendazole for treatment and maintenance of ovarian cancer

Gynecologic Oncology, Journal Year: 2020, Volume and Issue: 160(1), P. 302 - 311

Published: Oct. 31, 2020

Language: Английский

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