Docetaxel Pharmacokinetic Investigation In Sprague-Dawley Rats Using In-Vivo Tests After Oral And Transdermal Lipo-Nanosphere Administration

Abstract

Background: The FDA-approved medication docetaxel (DCX), which  shown promise in treating a number of cancer types.

Objective:DCX's significant gastrointestinal toxicity and high hydrophobicity, which result in low bioavailability with first-pass metabolism and P-glycoprotein efflux pumps, are the main causes of its restricted solubility, short duration of action, and instability.To increase DCX's stability and facilitate its efficient delivery to tumour tissues, a transdermal film containing docetaxel was created and placed into Lipo-Nanospheres.

Methods: 72 Sprague-Dawley male rats weighing 200±0.25g were used in this investigation. They were divided into two groups of 12 animals each. Rats received a dose of 16 mg of pure DCX suspension orally through gavage, and their skin was then coated with DCX Lipo-Nanosphere transdermal film. Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC) is used to measure DCX in rat plasma.

Results: For oral routes, the maximal effect (Cmax, Tmax, and AUC0-72) was Cmax=9361±11.14, Tmax=12 hours, and 34327.433±117 ng/h/ml; for transdermal routes, it was Cmax=11263±7.4, Tmax=6 hours, and 146336.87±243 ng/h/ml. The findings indicated that there was a significant difference (p<0.05) in the amount of time and concentration required to get the maximal effect (Cmax and Tmax) between transdermal Lipo-Nanosphere film and DCX-oral solution. After a single dose given for 72 hours, the transdermal method's relative bioavailability was more than four times greater than that of the oral route.

Conclusions: F10 transdermal film offers a 4.26-fold higher bioavailability than DCX oral suspension made of pure powder.