Antinociceptive effects of Cremophor EL orally administered to mice

Abstract

Surfactants are frequently used to improve solubilization of lipophilic drugs. Cremophor EL (CrEL) is a polyoxyethylated castor oil surfactant used to solubilize water-insoluble drugs such as anesthetic, antineoplastic, immunosuppressive and analgesic drugs, vitamins and new synthetic compounds, including potential analgesics. The antinociceptive effect of CrEL (3.2, 6.4 and 10.6 g/kg, in 10 ml/kg body weight, by gavage) on the abdominal writhing response induced by intraperitoneal administration of acetic acid (0.8%, 10 ml/kg body weight) and on the tail immersion test was investigated in mice. Control animals received castor oil (10 ml/kg body weight) or saline (0.9% NaCl, 10 ml/kg body weight). CrEL reduced nociception in a dose-dependent manner in both tests. At 10.6 g/kg, CrEL caused antinociception similar to that induced by dipyrone (300 mg/kg, by gavage) in the abdominal writhing test, and antinociception similar to that induced by morphine (20 mg/kg, by gavage) in the tail immersion test. The effect of castor oil was similar to that of saline in both assays. These data indicate that the appropriate controls should be used when evaluating the effects of potential antinociceptive agents dissolved in CrEL.

ZnCl2 exposure protects against behavioral and acetylcholinesterase changes induced by HgCl2

“…Nociception was assessed in the tail immersion test as described by Tabarelli et al (2003), with some changes. Rats were wrapped in a towel and 3.5 cm of tail was immersed in water bath (48 ± 1 °C).…”

Castor Oil-Based Biodegradable Polyesters

“…Due to its surfactant nature, this has been widely used in solublizing water insoluble drugs. Even though it is non toxic, many reports have suggested that the formulations of Cremophor EL with drugs induce serious complications such as anaphylactoid hypersensitivity, axanol swelling, degeneration, and demyelination …”

Genistein inhibits aggregation of exogenous amyloid-beta1–40 and alleviates astrogliosis in the hippocampus of rats

“…However, the mechanism by which CrEL improves the ability of neurons to resist Aβ is unknown. CrEL, used as a solvent for hydrophobic drugs, is associated with axonal damage in the peripheral nerves (Gelderblom et al, 2001), it has an antinociceptive effect (Tabarelli et al, 2003), and it limits the absorption of drugs in the gastrointestinal canal (Malingre et al, 2001). These observations show that the vehicle of drugs may have biological effects that influence the development of the pathology and, therefore, their effect should be considered before making any conclusion.…”