Intrinsic antitumor effect of tween 80

Introduction

Tween 80, also known as polysorbate 80, chemically called polyoxyethylene 20 sorbitan monooleate, is a light yellow to orange-yellow viscous liquid(picture 1). It is easily soluble in water, methanol, ethanol and ethyl acetate, and is very slightly soluble in mineral oil[1]. It is a hydrophilic nonionic surfactant and is one of the commonly used excipients in pharmaceutical preparations. Due to its long carbon chain structure in its structure, it has a good solubilization effect on lipophilic drugs, and is often used as a cosolvent, emulsifier and stabilizer in the preparation of insoluble pharmaceutical preparations. The molecular weight is 1309.7, and it is produced by the condensation of monooleate of sorbitol and other dehydration and double dehydration compounds with about 20 moles of ethylene oxide under alkaline conditions.

Picture 1 A bottle of Tween 80

Acute hypersensitivity reaction

Clinically, intravenous injection of Tween 80-containing injections, such as etoposide injection and docetaxel injection, often causes acute hypersensitivity reactions, especially the early occurrence rate of docetaxel injection is 5% to 40%. % (Severe, that is, more than the second category of allergy standards set by the National Cancer Institute is a minority) by giving glucocorticoids and antihistamines before surgery can be effectively improved. It is speculated that it is related to the oleic acid released by its hydrolysis in vivo. Studies have shown that oleic acid can promote the release of histamine in dogs and cause acute hypersensitivity reactions. Domestic studies have also been carried out on the allergic reactions caused by traditional Chinese medicine injections containing Tween 80 to dogs.

Peripheral neurotoxicity

American scientists found that "Tween 80 may cause the degeneration of cystic cells and cause peripheral neurotoxicity through the study of the effects of paclitaxel antitumor drugs on the nervous system. The cause of this adverse reaction may be the polyol in Tween 80. A polyethylene-like substance produced by the reaction of a compound with ethylene oxide.

Inhibits P-glycoprotein activity

P-glycoprotein plays an important role in the active drug transport process. Tween 80 can form giant micelles in blood and body fluids to encapsulate or chimeric protein molecules, which inhibit P-glycoprotein from participating in the drug transport process at the biomembrane interface.

Intrinsic antitumor effect

Tween 80 showed some antitumor activity in model animals, which may be related to the release of oleic acid. Research data show that oleic acid can inhibit the production of peroxides in the body and interfere with the growth of tumor cells.

Hepatotoxicity

The liver, kidneys, lungs and skin were found to have TU80-related changes. Liver changes include vacuolation of hepatocytes, eosinophils in sinusoids, eosinophilic bodies, green/brown staining of bile ducts, necrosis of hepatocytes, vacuolation of epithelial cells of renal convoluted tubules; pulmonary edema and necrosis; acute inflammation; skin Hyperemia, edema, necrosis, inflammation. Sweden reported a case of contact allergy with Tween 80 aerosol.

HPLC-ELSD method

The author used a C18 column with methanol-water as the mobile phase for gradient elution, and quickly pushed the Tween 80 in the preparation into a peak and quantified it with an ELDS detector to obtain ideal results.

HPLC-MS method

American scholars have used the HPL CE SI/MS method to measure the concentration of Tween 80 in the blood of patients who use docetaxel clinically at one time, so as to provide clinical safety monitoring data. The authors of the article used acetonitrile-chloroform (1:4) for solution extraction, using an ODS column with a particle size of 3.5 μm, and using methanol-water (9:1) as the mobile phase.

MALDI-TOF/MS method

American scholars used MALD IT OF/MS method to analyze the polymer type and composition of Tween series surfactants, and found that such substances are composed of polyethylene glycol, polyethylene glycol ester, isosorbide polyethylene glycol ester, dehydrated It is composed of sorbitol polyethylene glycol ester, polysorbate monooleate, polyethylene glycol trioleate, sorbitol polyethylene glycol ester, etc. The complexity of the spectrum is related to the fatty acid moiety formed, and the Tween 80 has the simplest spectrum of all compounds.

Reference

1 Feng Zongcai, Zhou Xiaoping Synthesis and emulsifying properties of modified Tween-20 [J] Synthetic chemistry, 2005, (2): 190-192