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Updated: Jan 30, 2026
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Novel Approaches for Efficient Delivery of Tyrosine Kinase Inhibitors
Zahra Moradpour1, Leila Barghi
1Department of Pharmaceutical biotechnology, Urmia University of medical sciences, Urmia, Iran.
Abstract:
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.
Insights
Targeted delivery systems enhance cancer treatment by improving the efficacy of tyrosine kinase inhibitors (TKIs) and reducing side effects. These advanced formulations address drug solubility and enable combination therapies for better patient outcomes.
Area of Science:
- Oncology
- Nanotechnology
- Pharmacology
Background:
- Epidermal growth factor receptors (EGFRs) are key therapeutic targets in cancer, particularly when overexpressed.
- Small molecule tyrosine kinase inhibitors (SMTKIs) and monoclonal antibodies have been developed, but face challenges with specificity and side effects.
- Drug formulation issues like poor solubility and dissolution rates limit the efficacy of many kinase inhibitors.
Purpose of the Study:
- To review recent advances in developing targeted delivery systems for tyrosine kinase inhibitors (TKIs).
- To highlight strategies for overcoming formulation challenges and improving TKI therapeutic potential.
- To explore the benefits of combination therapies enabled by advanced delivery systems.
Main Methods:
- Review of literature on various targeted delivery systems including dendrimers, nanoparticles (polymeric, magnetic), and lipid-based systems (liposomes, SLN, NLC).
- Analysis of formulation strategies to enhance drug solubility and dissolution rates (e.g., particle size reduction, self-emulsification, complexation, amorphous solid dispersion).
- Examination of combination therapy approaches using TKIs with chemotherapy, biopharmaceuticals, or other TKIs.
Main Results:
- Targeted delivery systems can improve drug distribution to target organs, reducing dose-dependent side effects.
- Advanced formulation techniques successfully address physicochemical challenges of TKIs, enhancing their therapeutic performance.
- New delivery systems facilitate synergistic combination therapies, potentially overcoming drug resistance and improving patient compliance.
Conclusions:
- Targeted delivery systems represent a significant advancement in optimizing TKI therapy for cancer.
- These systems offer a promising approach to enhance efficacy, minimize toxicity, and enable novel combination treatment strategies.
- Continued development in drug delivery holds potential for more effective and patient-friendly cancer treatments.
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