Imatinib Mesylate

Bhirud D, et al. Carbohydrate Polymers, 2025, 348(B), 122935.

Chitosan-based nanoparticles (CS-IMT-NPs) were synthesized to facilitate the targeted delivery of Imatinib Mesylate (IMT) to colon cancer cells. Further modification of the nanoparticles was performed by surface coating with D-α-tocopheryl polyethylene glycol succinate (TPGS), enhancing their bio-distribution, permeability, and bioavailability by promoting their internalization into specific cellular organelles.
Preparation of Imatinib Mesylate Chitosan Nanoparticles
To dissolve chitosan powder, a 1% (v/v) acetic acid solution was used, and the mixture was stirred on a magnetic stirrer at 25 °C and 100 rpm for 5 hours. Afterward, 1 M NaOH solution was added to maintain the pH at 5. The stability and homogeneity of the solution were further improved by adding the anionic surfactant Polysorbate 80. Following the stirring process, the desired amount of IMT mesylate was slowly incorporated into the chitosan solution containing Polysorbate 80. The mixture was stirred for an additional 25 minutes.
A 7 mg/mL sodium tripolyphosphate (TPP) solution was prepared, which is crucial for ion gelation, induced by the interaction between the positively charged amino groups of chitosan and the negatively charged phosphate groups of TPP. By adjusting the pH to 2, the TPP solution became acidic, enhancing the positive charge on chitosan's amino groups. When the TPP solution was added dropwise to the chitosan-IMT solution under stirring, electrostatic interactions occurred between the oppositely charged ions. The resulting solution was then homogenized for 15 minutes at an appropriate speed using a high-speed homogenizer. The nanoparticles were subsequently centrifuged at 4000 rpm and washed with deionized water to purify the particles. The final sample was freeze-dried for further characterization.
Surface Coating of Chitosan/Imatinib Mesylate Nanoparticles with TPGS
To successfully coat TPGS onto the chitosan nanoparticles and alter the chitosan structure, a carbodiimide coupling reaction was employed using reagents such as EDC and NHS. N-Hydroxysuccinimide (NHS) is commonly used in conjunction with EDC to stabilize the intermediate formed during the coupling reaction. The carbodiimide coupling reaction forms amide bonds between TPGS and chitosan, effectively linking TPGS to the surface of the nanoparticles. To load IMT into the TPGS-coated chitosan nanoparticles, 1 mL of phosphate-buffered saline (PBS, pH 7.4), EDC, and NHS (in a 1:3 ratio) were mixed with the prepared nanoparticles and stirred for 8 hours using a magnetic stirrer.

Ghosal S, et al. Computers in Biology and Medicine, 2024, 177, 108683.

The study explores the interaction of imatinib mesylate with various G-Quadruplex (GQ) DNA structures, utilizing a combination of multispectroscopic techniques and molecular modeling. The results reveal that imatinib mesylate preferentially binds to vascular endothelial growth factor (VEGF) GQ DNA over other GQ DNA structures, such as C-Myc and H-Telo, as well as duplex DNA.
Circular dichroism (CD) spectroscopy suggests that imatinib mesylate stabilizes the pre-folded parallel conformation of VEGF GQ DNA without altering its structural integrity. π-π stacking interactions between imatinib's aromatic groups and the G-quartets are identified as key drivers of the binding affinity. Additionally, UV-melting studies indicate that the drug enhances the thermal stability of the VEGF GQ DNA, while fluorescence spectroscopy reveals a significant increase in the fluorescence intensity of imatinib mesylate upon binding to the VEGF GQ sequence. Molecular docking and in silico analysis further support these findings, indicating that imatinib mesylate is a strong binder to the VEGF GQ DNA structure.
These findings suggest that imatinib mesylate may be a valuable tool for targeting and regulating gene expression in cancerous cells through its selective interaction with VEGF GQ DNA, providing a novel mechanism of action in cancer therapy. This study represents the first report of imatinib mesylate's preferential interaction with VEGF GQ DNA, offering potential for its future use in gene regulation and cancer treatment.

Pang S, et al. Bioactive Materials, 2024, 38, 124-136.

Imatinib Mesylate (IM) can be used to develop a pH-responsive, sustained-release hydrogel for drug delivery, utilizing the metal-organic framework (MOF) ZIF-8 as the drug carrier. This approach enables controlled drug release, enhancing the effective dose of the drug at the peak of adhesion formation, thereby improving therapeutic outcomes. The results demonstrate that IM inhibits tendon adhesion formation by suppressing the PDGFRβ/ERK/STAT3/CLDN1 signaling pathway. Furthermore, the ZIF-8-loaded hydrogel exhibited superior physical properties and drug release profiles compared to the drug-loaded hydrogel alone, showing enhanced effectiveness in preventing and treating tendon adhesions.
Synthesis of IM@ZIF-8: To synthesize IM@ZIF-8, 2.5 mL of imatinib mesylate (IM) solution (2, 2.5, or 8 mg/mL) was stirred in 100 mL of zinc acetate solution (Zn(CH₃COO)₂·2H₂O, 43.9 mg/mL) for 15 minutes. Next, 10 mL of 2-methylimidazole (0.12 g/mL) was added, and the mixture was stirred at 30°C for 4 hours, resulting in an opaque solution. After concentration, the mixture was washed sequentially with ethanol and water, then naturally dried to obtain the IM@ZIF-8 composite at varying dry weights. Therefore, ZIF-8 can also be synthesized independently of the drug.
Synthesis of Hydrogel: CEC polymer and OHA were each dissolved in deionized water at a concentration of 2% (wt/vol). The CEC and OHA solutions were then mixed at 37°C to form a hydrogel, with a molar ratio of CEC to OHA set at 1:1.
Synthesis of IM@ZIF-8@Gel: To prepare the IM@ZIF-8@Gel, the required amount of synthesized nanoparticles was first dissolved in a 2% (wt/vol) OHA solution. This nanoparticle-containing OHA solution was then mixed with a 2% (wt/vol) CEC solution at 37°C.