Cyclodextrin-Based Niosomal Delivery of Imatinib against A549 Nonsmall Cell Lung Cancer Cells - read online

Q: Why is delivering imatinib to lung cancer cells challenging in current therapy?

Imatinib’s clinical use is limited by poor water solubility and the onset of drug resistance, reducing practical effectiveness.

Q: Which cyclodextrins were studied for forming the IMB inclusion complex?

The study evaluates water-soluble IMB/cyclodextrin complexes focusing on high affinity with γCD and HPγCD.

Q: How did TPGS-based IMB/CD-loaded niosomes affect A549 cells?

TPGS-based niosomes significantly enhanced cellular uptake and induced apoptosis in A549 cells, producing potent cytotoxicity with an IC50 value of 5 μM.

Sep 28, 2026

Uploaded by Danger Angel

Lung cancer remains a major cause of cancer-related deaths worldwide, and effective therapy depends on delivering drugs that selectively target cancer cells at the right dose. This study develops a water-soluble IMB/cyclodextrin inclusion complex and characterizes its high affinity for γCD and HPγCD. Niosomes loaded with the IMB/CD complex, with or without TPGS, are formulated via thin-film hydration and show nanoscale size, low polydispersity, negative zeta potential, and high entrapment efficiency. TPGS-based niosomes markedly enhance uptake and trigger apoptosis in A549 nonsmall cell lung cancer cells, with strong cytotoxicity (IC50 5 μM).

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Abstract

Introduction

This article is licensed under CC-BY-NC-ND 4.0 [http://pubs.acs.org/journal/acsodf](http://pubs.acs.org/journal/acsodf) Article Cyclodextrin-Based Niosomal Delivery of Imatinib against A549 Nonsmall Cell Lung Cancer Cells Hay Marn Hnin, Theingi Tun, Chaisak Chansriniyom, Natsaranyatron Singharajkomron, Varisa Pongrakhananon, Thorsteinn Loftsson, and Phatsawee Jansook* Cite This: ACS Omega 2025, 10, 62585−62598 Read Online | | | | | | --- | --- | --- | --- | | ACCESS | Metrics & More | | Article Recommendations | 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 complexloaded 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 complexloaded niosomes could be promising for efficient IMB delivery to nonsmall cell lung cancer A549 cells and potentially contributing to future lung cancer therapy. 1. INTRODUCTION Lung cancer represents one of the major prevalent cancer types and remains a primary cause of cancer-related deaths worldwide.1 Nonsmall cell lung cancer (NSCLC) accounts about 85% of all lung cancer diagnoses and occurs almost exclusively in smokers.2 Due to the late manifestation of clinical symptoms, most NSCLC patients are presented as advanced stage at the time of diagnosis.3 Subsequently, life expectancy is limited, with most patients exhibiting a median overall survival of around 10 to 12 months.3 In addition, a response rate to current chemotherapeutics is also limited and only 20% of NSCLC patients resulted in tumor shrinkage.4 Various molecular markers have been shown to link with pathogenesis and prognosis of NSCLC.3,5 Interestingly, 50 − 80% of tumor specimens of NSCLC patients are shown to be overexpression of a platelet-derived growth factor (PDGF-β).6 The phosphorylation ofits receptor (PDGFR-β) contributes to enhance stimulation of stromal growth and participation in completion of the tumor angiogenic process, thereby disrupting interstitial homeostasis and higher tumor interstitial fluid pressure (IFP).6,7 In fact, the increased pressure within the core of solid tumor often disrupts the pressure gradient across microvessels, thereby reducing transport of therapeutic agents from the bloodstream into the interstitial space. The current therapeutic strategies used to lower IFP involve the blocking of cytokines such as PDGF, transforming growth factor and vascular endothelial growth factor, and decompressing of tumor vasculature through the tumor cell death.4 | Received: June 30, 2025
Revised: October 29, 2025
Accepted: December 10, 2025
Published: December 14, 2025 | | | --- | --- | © 2025 The Authors. Published by American Chemical Society 62585 [https://doi.org/10.1021/acsomega.5c06264](https://doi.org/10.1021/acsomega.5c06264) ACS Omega 2025, 10, 62585−62598 Imatinib (IMB), PDGFR-β-specific tyrosine kinase inhibitor, is clinically approv

FAQs

Why is delivering imatinib to lung cancer cells challenging in current therapy?

Imatinib’s clinical use is limited by poor water solubility and the onset of drug resistance, reducing practical effectiveness.

Which cyclodextrins were studied for forming the IMB inclusion complex?

The study evaluates water-soluble IMB/cyclodextrin complexes focusing on high affinity with γCD and HPγCD.

How did TPGS-based IMB/CD-loaded niosomes affect A549 cells?

TPGS-based niosomes significantly enhanced cellular uptake and induced apoptosis in A549 cells, producing potent cytotoxicity with an IC50 value of 5 μM.

Sep 28, 2026

Uploaded by Danger Angel