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Liposomal Amodiaquine for Localized Therapy of Non-Small Cell Lung Cancer (NSCLC)
Meghana Mokashi1, Mimansa Goyal1, Naveen Rajana1
1Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA.
Abstract:
Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases and remains associated with a poor five-year overall survival rate (~ 17.4%). Current therapies are limited by suboptimal efficacy and safety, underscoring the need for novel interventions. This study investigates the repurposing of amodiaquine (AQ), an anti-malarial drug, formulated into inhalable liposomes for targeted NSCLC therapy. The AQ-loaded liposomes exhibited favorable physicochemical properties, including sub-200 nm particle size, low polydispersity index (< 0.3), high drug loading (≈40%), and stability for over two months. In-vitro aerosolization studies demonstrated efficient lung-targeting potential, with > 70% of particles depositing in the deep lung regions. Cytotoxicity assays revealed significantly enhanced anticancer potency of AQ-liposomes compared to the free drug in NSCLC cell lines. Furthermore, clonogenic and wound healing assays showed a marked reduction in cancer cell proliferation and migration. Mechanistically, caspase assays indicated elevated apoptosis in AQ-liposome-treated cells. In 3D spheroid models, AQ-liposomes disrupted spheroid integrity more effectively than AQ alone, confirmed by live/dead staining. Collectively, these findings support the potential of inhalable AQ liposomes as a promising therapeutic strategy for NSCLC. Future in vivo studies and clinical evaluation are warranted to validate translational feasibility and therapeutic efficacy in NSCLC management.
Insights
This study repurposed the anti-malarial drug amodiaquine (AQ) into inhalable liposomes for non-small cell lung cancer (NSCLC) therapy. These AQ liposomes demonstrated enhanced anticancer effects and efficient lung delivery, showing promise for NSCLC treatment.
Area of Science:
- Oncology
- Nanotechnology
- Pharmacology
Background:
- Non-small cell lung cancer (NSCLC) has a poor prognosis, with current treatments facing efficacy and safety limitations.
- Novel therapeutic strategies are urgently needed to improve outcomes for NSCLC patients.
- Drug repurposing offers a potential avenue for developing new cancer therapies.
Purpose of the Study:
- To investigate the potential of amodiaquine (AQ), an anti-malarial drug, repurposed as inhalable liposomes for targeted NSCLC therapy.
- To evaluate the physicochemical properties, lung deposition, and in vitro anticancer efficacy of AQ-loaded liposomes.
- To elucidate the mechanisms underlying the anti-NSCLC effects of AQ liposomes.
Main Methods:
- Formulation of amodiaquine (AQ) into inhalable liposomes with optimized physicochemical characteristics.
- In vitro aerosolization studies to assess lung deposition efficiency.
- Cytotoxicity, clonogenic, wound healing, and caspase assays on NSCLC cell lines.
- Evaluation in 3D spheroid models using live/dead staining.
Main Results:
- AQ-loaded liposomes displayed favorable properties: sub-200 nm size, low polydispersity, high drug loading (~40%), and >2 months stability.
- In vitro aerosolization confirmed efficient deep lung deposition (>70%).
- AQ liposomes exhibited superior in vitro anticancer activity, reducing NSCLC cell proliferation, migration, and inducing apoptosis compared to free AQ.
Conclusions:
- Inhalable amodiaquine liposomes show significant potential as a targeted therapy for non-small cell lung cancer.
- The formulation demonstrates enhanced efficacy and favorable delivery characteristics for NSCLC treatment.
- Further in vivo and clinical studies are warranted to confirm the therapeutic utility of AQ liposomes in NSCLC management.
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