Advancements in the oral delivery of Docetaxel: challenges, current state-of-the-art and future trends

Muhammad Farhan Sohail,1–3 Mubashar Rehman,4,5 Hafiz Shoaib Sarwar,2 Sara Naveed,1 Omer Salman,6 Nadeem Irfan Bukhari,7 Irshad Hussain,3 Thomas J Webster,5 Gul Shahnaz21Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore Campus, Lahore, 2Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 3Department of Chemistry, SBA School of Science and Engineering (SBASSE), Lahore University of Management Sciences (LUMS), Lahore, 4Department of Pharmacy, University of Lahore-Gujrat Campus, Gujrat, 5Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 6Department of Pharmacy, University of Lahore, Lahore Campus, 7University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore, Pakistan Abstract: The oral delivery of cancer chemotherapeutic drugs is challenging due to low bioavailability, gastrointestinal side effects, first-pass metabolism and P-glycoprotein efflux pumps. Thus, chemotherapeutic drugs, including Docetaxel, are administered via an intravenous route, which poses many disadvantages of its own. Recent advances in pharmaceutical research have focused on designing new and efficient drug delivery systems for site-specific targeting, thus leading to improved bioavailability and pharmacokinetics. A decent number of studies have been reported for the safe and effective oral delivery of Docetaxel. These nanocarriers, including liposomes, polymeric nanoparticles, metallic nanoparticles, hybrid nanoparticles, dendrimers and so on, have shown promising results in research papers and clinical trials. The present article comprehensively reviews the research efforts made so far in designing various advancements in the oral delivery of Docetaxel. Different strategies to improve oral bioavailability, prevent first-pass metabolism and inhibition of efflux pumping leading to improved pharmacokinetics and anticancer activity are discussed. The final portion of this review article presents key issues such as safety of nanomaterials, regulatory approval and future trends in nanomedicine research. Keywords: anticancer, permeability enhancement, solubility enhancement, P-glycoproteins, efflux pump, first-pass metabolism