Pharmacodynamic study using a chemotherapeutically induced emesis model

Rats and mice respond to emesis stimulating factors by induction of pica i.e. the consumption of a substance without nutritional value such as kaolin. Thus, pica has been suggested to be analogue to vomiting in species that do not vomit⁴³. Cisplatin is a cancer chemotherapeutic agent which was reported to induce pica in a species endowed with this reflex, manifested by an increase in kaolin intake, a decrease in the food and water intake and a decrease in the gastric emptying, resulting in an increase in the weight of the stomach content. The experimental procedures were approved by the ethical committee of faculty of pharmacy, Ain Shams University (approval number ASU 94).

Six groups of adult male albino Wistar (130–150 gms) rats were used. Each group included 8 rats intraperitonially (i.p.) injected by cisplatin as a pica inducing drug. Kaolin was mixed with 1% gum Arabic to prepare a thick paste of kaolin (China clay). It was further extruded, dried at room temperature, and then cut into pellets to form rods with a similar size to the normal food pellets. For a 3 day habituation period prior to the start of the experiment each animal was supplied by food, water and kaolin after being placed in an individual cage, and their food, water and kaolin consumption was assessed. The groups were divided as follows:

Group I: Normal “control” group (given distilled water orally using the oral tube without administration of cisplatin injection).

Group II: Induced “reference” group (given distilled water orally by the oral tube before i.p. cisplatin injection).

Group III: Standard group (given crushed Dramenex® marketed product orally using the oral tube 15 min before i.p. cisplatin injection, at a dose of 10 mg/kg equivalent to 1.3–1.5 mg DMH per rat).

Group IV: PEVs formula test group (Intranasal administration of 25 µl of the PEVs formula in each nostril before i.p. cisplatin injection by 15 min, corresponding to a dose of 1 mg DMH per rat).

Group V: Mucoadhesive thermosensitive in situ gelling group (Intranasal administration of the in situ gelling system corresponding to a dose of 1 mg DMH per rat).

Group VI: Nanocomposite formula test group (Intranasal administration of the DMH in situ gelling nanocomposite formula before i.p. cisplatin injection by 15 min, corresponding to a dose of 1 mg DMH per rat).