Effective Oral Administration of an Antitumorigenic Nanoformulated Titanium Complex.
Gilad NahariOri BraitbardLiraz LarushJacob HochmanEdit Y TshuvaPublished in: ChemMedChem (2020)
Orally administered anticancer drugs facilitate treatment, but the acidic conditions in the stomach often challenge their availability. PhenolaTi is a TiIV -based nontoxic anticancer drug with marked in-vivo efficacy. We report that nanoformulation protects phenolaTi from decomposition in stomach-like conditions. This is evidenced by similar NMR characteristics and similar in-vitro cytotoxicity toward murine (CT-26) and human (HT-29) colon cancer cells before and after incubation of nanoformulated phenolaTi (phenolaTi-F) at pH 2, unlike results with the unformulated form of the complex. Furthermore, administration of phenolaTi-F in animal drinking water revealed a notable inhibition of tumor growth in Balb/c and immune-deficient (Nude) mice inoculated with CT-26 and HT-29 cells, respectively. In-vivo efficacy was at least similar to that of the corresponding intraperitoneal treatment with phenolaTi-F and the clinically employed oral drug, capecitabine. No body weight loss or clinical signs of toxicity were evident in the phenolaTi-F-treated animals. These findings demonstrate a new convenient mode of cancer treatment through oral administration by safe titanium-based drugs.
Keyphrases
- drinking water
- weight loss
- computed tomography
- induced apoptosis
- endothelial cells
- magnetic resonance imaging
- drug induced
- emergency department
- image quality
- contrast enhanced
- type diabetes
- high resolution
- magnetic resonance
- oxidative stress
- bariatric surgery
- cell cycle arrest
- dual energy
- ionic liquid
- health risk assessment
- risk assessment
- combination therapy
- skeletal muscle
- roux en y gastric bypass
- gastric bypass
- cell proliferation
- induced pluripotent stem cells
- smoking cessation