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

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.

Overcoming Biological Barriers in Neuroblastoma Therapy: The Vascular Targeting Approach with Liposomal Drug Nanocarriers

“…Thus, much effort has been made for increasing the delivery and penetration of liposomal‐carried drugs into tumors, including NB . Although the so‐called “enhanced permeability and retention effect” (owing to leaky vessels typically present in tumors) has served as a rationale for using nanoformulated drugs to treat solid tumors, it is generally believed that this effect is not sufficient to guarantee uniform drug delivery to all tumor regions, because of the many physiological barriers, mentioned above, present in tumor tissues .…”

Development and Evaluation of Docetaxel-Phospholipid Complex Loaded Self-Microemulsifying Drug Delivery System: Optimization and In Vitro/Ex Vivo Studies

“…However, the development of oral formulation has been difficult, because of the low oral bioavailability (<5%) of DTX [ 6 ]. The BCS class IV drug, DTX, is partially insoluble in water, and has low permeability across the gastrointestinal (GI) epithelium, due to P-glycoprotein (P-gp) mediated efflux, which limits the GI absorption and oral bioavailability of DTX [ 7 ].…”

Inclusion Complex of Docetaxel with Sulfobutyl Ether β-Cyclodextrin: Preparation, In Vitro Cytotoxicity and In Vivo Safety

“…Docetaxel has presented a broad spectrum of activity against various kinds of tumors. Because of its poor aqueous solubility (1–5 μg·mL −1 in plain water), the commercial docetaxel (Taxoter ® ) is currently formulated in a combination of tween 80 and ethanol to improve it solubility [ 15 , 16 , 17 ]. Studies have shown that preparations are known to cause severe peripheral neuropathy and allergic reactions.…”