Novel Approaches for Efficient Delivery of Tyrosine Kinase Inhibitors

Epidermal growth factor receptors (EGFRs) have potential to be considered as therapeutic target
for cancer treatment especially in cancer patients with overexpression of EGFR. Cetuximab as a first monoclonal
antibody and Imatinib as the first small molecule tyrosine kinase inhibitor (SMTKI) were approved by FDA in
1998 and 2001. About 28 SMTKIs have been approved until 2015 and a large number of compound with kinase
inhibitory activity are at the different phases of clinical trials. Although Kinase inhibitors target specific
intracellular pathways, their tissue or cellular distribution are not specific. So treatment with these drugs causes
serious dose dependent side effects. Targeted delivery of kinase inhibitors via dendrimers, polymeric
nanoparticles, magnetic nanoparticles and lipid based delivery systems such as liposomes, solid lipid nanoparticles
(SLN) and nanostructured lipid carriers (NLC) can lead to reduction of side effects and improving therapeutic
efficacy of the drugs in the target organs. Furthermore formulation of these drugs is challenged by their
physicochemical properties such as solubility and dissolution rate. The main approaches in order to increase
dissolution rate, are particle size reduction, self-emulsification, cyclodextrin complexation, crystal modification
and amorphous solid dispersion. Synergistic therapeutic effect, decreased side effects and drug resistant, reduced
cost and increased patient compliance are the advantages associated with using combination therapy especially in
the treatment of cancer. Combination of TKIs with chemotherapeutic agents or biopharmaceuticals such as
monoclonal antibodies and oligonucleotides and also combination of two TKIs within one formulation is possible
by new targeting delivery systems. This article reviews the recent advances in the design and development of
delivery systems for TKIs.
__________________________________________________________________________________________