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.

Keywords: docetaxel; drug delivery; lung cancer; nanoparticles; non-small cell lung cancer (NSCLC).

Figure 1

Chemical structure of docetaxel (left) and paclitaxel (right).

Figure 2

Some of the possible mechanisms of taxane resistance, such as modification of tubulin isoform composition, mutation of tubulin, mitotic checkpoints signaling mutation/defects, and ABC transporter efflux of taxane. (Illustrated through Biorender.com).

Figure 3

Pulmonary deposition of inhaled particles in healthy lung-dependent on the particle size (Illustrated through Biorender.com).

Figure 4

Structure of solid lipid nanoparticles (Illustrated through Biorender.com).

Figure 5

Structure of various models of incorporation of active compounds into SLNs: (a) solid solution (homogenous matrix) model, (b) drug-enriched shell model, (c) drug-enriched core model (Illustrated through Biorender.com).

Figure 6

Illustration of liposome and its different drug-loading. The drug can be loaded in the liposomes by: (1) passive loading. The lipophilic drug is entrapped in the bilayers, and the hydrophilic drug is entrapped in the aqueous core. (2) Active loading where pH gradient method is applied (Illustrated through Biorender.com).

Figure 7

Structure of lipid-polymer hybrid nanoparticles (LPHNPs). LPHNPs is made up of polymeric core loaded with a drug(s). The polymeric core is surrounded by a lipid/lipid-polyethylene(glycol) (lipid-PEG) monolayer. The nanoparticle is functionalized by conjugating ligands onto the PEG (illustrated through Biorender.com).

Figure 8

Structure of carbon nanotubes as originated from a graphene sheet. A graphene sheet is rolled to form SWCNT, and multiple sheets of graphene with different sizes are needed to form MWCNT (Illustrated through Biorender.com).