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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

Akhtar Nadhman,1–3 Malik Ihsanullah Khan,1,2 Samina Nazir,4 Momin Khan,1,5 Gul Shahnaz,6 Abida Raza,2 Dilawar Farhan Shams,7 Masoom Yasinzai1,3 1Department of Biotechnology, Faculty of Biological Sciences, Quaid-i-Azam University, 2Nuclear Medicine Oncology and Radiotherapy Institute, 3Centre for Interdisciplinary Research in Basic Sciences (CIRBS), International Islamic University, 4Nanosciences and Catalysis Division, National Centre for Physics, Quaid-i-Azam University Campus, Islamabad, 5Department of Microbiology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, 6Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 7Department of Environmental Sciences, Abdul Wali Khan University Mardan, Mardan, Pakistan Abstract: Lipid and protein oxidation are well-known manifestations of free radical activity and oxidative stress. The current study investigated extermination of Leishmania tropica promastigotes induced by lipid and protein oxidation with reactive oxygen species produced by PEGylated metal-based nanoparticles. The synthesized photodynamic therapy-based doped and nondoped zinc oxide nanoparticles were activated in daylight that produced reactive oxygen species in the immediate environment. Lipid and protein oxidation did not occur in dark. The major lipid peroxidation derivatives comprised of conjugated dienes, lipid hydroperoxides, and malondialdehyde whereas water, ethane, methanol, and ethanol were found as the end products. Proteins were oxidized to carbonyls, hydroperoxides, and thiol degrading products. Interestingly, lipid hydroperoxides were produced by more than twofold of the protein hydroperoxides, indicating higher degradation of lipids compared to proteins. The in vitro evidence represented a significant contribution of the involvement of both lipid and protein oxidation in the annihilated antipromastigote effect of nanoparticles. Keywords: lipid peroxidation, protein oxidation, Leishmania tropica, zinc oxide (ZnO), nanoparticles, reactive oxygen species (ROS), photodynamic therapy (PDT), doping