Nanotechnology of Tyrosine Kinase Inhibitors in Cancer Therapy: A Perspective

Abstract

Nanotechnology is an important application in modern cancer therapy. In comparison with conventional drug formulations, nanoparticles ensure better penetration into the tumor mass by exploiting the enhanced permeability and retention effect, longer blood circulation times by a reduced renal excretion and a decrease in side effects and drug accumulation in healthy tissues. The most significant classes of nanoparticles (i.e., liposomes, inorganic and organic nanoparticles) are here discussed with a particular focus on their use as delivery systems for small molecule tyrosine kinase inhibitors (TKIs). A number of these new compounds (e.g., Imatinib, Dasatinib, Ponatinib) have been approved as first-line therapy in different cancer types but their clinical use is limited by poor solubility and oral bioavailability. Consequently, new nanoparticle systems are necessary to ameliorate formulations and reduce toxicity. In this review, some of the most important TKIs are reported, focusing on ongoing clinical studies, and the recent drug delivery systems for these molecules are investigated.

Keywords: EPR; drug delivery; nanoparticles; tyrosine kinase inhibitors.

Figure 1

Chemical structure of selected tyrosine kinase inhibitors (TKIs).

Figure 2

Schematic representation of inorganic nanoparticles (AgNPs, AuNPs, MNPs and PSi NPs) [48].

Figure 3

Different types of lipid-based nanoparticles. (A) Liposomes; (B) solid lipid nanoparticles (SLNs); (C) nanostructured lipid carriers (NLCs) [70].

Figure 4

Schematic representation of nanocapsule and nanosphere structure [71].