Cyclodextrin-Based Niosomal Delivery of Imatinib against A549 Nonsmall Cell Lung Cancer Cells
Hay Marn Hnin1, Theingi Tun1, Chaisak Chansriniyom2,3
1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand.
Abstract:
Lung cancer remains a significant cause of cancer-related deaths globally. The effective cancer treatment aims to deliver drugs that specifically target cancer cells at the optimal dose. Imatinib (IMB), a selective kinase inhibitor, has demonstrated therapeutic efficacy against lung cancer. However, its use is often limited because of low solubility in water. This study investigated water-soluble IMB/cyclodextrin (CD) inclusion complex formation. IMB demonstrated a high affinity for γCD and HPγCD, as evidenced by phase-solubility studies, solid- and solution-state characterizations, and molecular docking study. IMB/CD complex-loaded niosomes in the presence and absence of D-alpha-tocopheryl polyethylene glycol succinate (TPGS) were fabricated using a thin-film hydration method. The prepared niosomal formulations showed nanoscale particle sizes (126-163 nm) with a low polydispersity index (<0.2), a negative zeta potential value (-3.65 to -13.67 mV), and % entrapment efficiency of 59-78%. The novel TPGS-based niosomes loaded with the IMB/CD complex significantly enhanced cellular uptake and induced apoptosis in A549 cells, exhibiting potent cytotoxicity with an IC50 value of 5 μM. These results indicate that our developed IMB/CD complex-loaded niosomes could be promising for efficient IMB delivery to nonsmall cell lung cancer A549 cells and potentially contributing to future lung cancer therapy.
Insights
This study developed water-soluble Imatinib/cyclodextrin complexes encapsulated in niosomes for lung cancer treatment. These novel formulations enhance drug delivery and exhibit potent cytotoxicity against A549 cancer cells.
Area of Science:
- Nanotechnology
- Pharmaceutical Sciences
- Oncology
Background:
- Lung cancer is a leading cause of cancer mortality worldwide.
- Effective treatment requires targeted drug delivery at optimal doses.
- Imatinib (IMB), a kinase inhibitor, shows efficacy but suffers from poor water solubility.
Purpose of the Study:
- To develop a water-soluble Imatinib/cyclodextrin (CD) inclusion complex.
- To formulate IMB/CD complexes into niosomes for enhanced drug delivery.
- To evaluate the efficacy of IMB/CD complex-loaded niosomes in A549 lung cancer cells.
Main Methods:
- Phase-solubility studies and molecular docking to assess IMB/CD complex formation.
- Thin-film hydration method to fabricate niosomes loaded with IMB/CD complexes.
- Characterization of niosomal formulations (particle size, zeta potential, entrapment efficiency) and assessment of cytotoxicity, cellular uptake, and apoptosis induction in A549 cells.
Main Results:
- Imatinib demonstrated high affinity for gamma-cyclodextrin (γCD) and hydroxypropyl-gamma-cyclodextrin (HPγCD).
- Niosomal formulations exhibited nanoscale particle sizes (126-163 nm), low polydispersity, and good entrapment efficiency (59-78%).
- TPGS-based niosomes significantly enhanced cellular uptake and induced apoptosis, showing potent cytotoxicity with an IC50 of 5 μM in A549 cells.
Conclusions:
- Developed IMB/CD complex-loaded niosomes are a promising strategy for improving IMB delivery.
- The novel formulations demonstrate enhanced efficacy against nonsmall cell lung cancer A549 cells.
- This approach holds potential for advancing future lung cancer therapies.
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