Advances in Nanocarriers for Effective Delivery of Docetaxel in the Treatment of Lung Cancer: An Overview

Abstract

Docetaxel (DCX) is a highly effective chemotherapeutic drug used in the treatment of different types of cancer, including non-small cell lung cancer (NSCLC). The drug is known to have low oral bioavailability due to its low aqueous solubility, poor membrane permeability and susceptibility to hepatic first-pass metabolism. To mitigate these problems, DCX is administered via the intravenous route. Currently, DCX is commercially available as a single vial that contains polysorbate 80 and ethanol to solubilize the poorly soluble drug. However, this formulation causes short- and long-term side effects, including hypersensitivity, febrile neutropenia, fatigue, fluid retention, and peripheral neuropathy. DCX is also a substrate to the drug efflux pump P-glycoprotein (P-gp) that would reduce its concentration within the vicinity of the cells and lead to the development of drug resistance. Hence, the incorporation of DCX into various nanocarrier systems has garnered a significant amount of attention in recent years to overcome these drawbacks. The surfaces of these drug-delivery systems indeed can be functionalized by modification with different ligands for smart targeting towards cancerous cells. This article provides an overview of the latest nanotechnological approaches and the delivery systems that were developed for passive and active delivery of DCX via different routes of administration for the treatment of lung cancer.

The Nanosystems Involved in Treating Lung Cancer

“…One might find it interesting that even the most recent reference reviews [ 171 , 172 ] on the specific theme of nanocarriers suitable for lung cancer treatment recognize the great number of doubts and burdens that are still to be considered in this niched research area. At the moment, only a few experiments have apparently been conducted with the specific aim of targeting lung cancer via nanoparticles, with the great majority of them focusing rather on the usage of these nano-sized carriers in oncology therapies [ 173 ].…”

Advanced Nanoparticle-Based Drug Delivery Systems and Their Cellular Evaluation for Non-Small Cell Lung Cancer Treatment

“…There are specific challenges that need to be considered to ensure an efficient pulmonary delivery of NDDS. The structure of the respiratory system and lung clearance mechanism may complicate the effort to ensure a sufficient amount of drug-encapsulated NDDS are accumulated at the cancer site [ 76 , 77 , 78 ]. The size of NDDS is of concern, as particles in the nanometer range are usually expelled during normal breathing.…”

“…Similarly, selective targeting of CD44-overexpressing NSCLC cells by hyaluronan-based nanoparticles has been observed in 2D and 3D cultures and in in vivo orthotopic lung cancer models. The nanoparticles provided active targeting partially mediated by CD44 and were also found to demonstrate less toxicity with improved antitumor efficiency [ 76 , 77 , 78 ]. Despite its robustness and functional relevance to native tissues and organs, the dynamic transport of nanotherapeutics in a 3D culture system is often overlooked.…”

Onco-Receptors Targeting in Lung Cancer via Application of Surface-Modified and Hybrid Nanoparticles: A Cross-Disciplinary Review

“…It is worth mentioning here that some types of EPR enhancers like bradykinin (kinin), nitric acid, peroxynitrite, prostaglandins, etc. may cause hypertension that could enhance tumor extrusion [23].…”