Microfluidic Encapsulation of Amiodarone in Lipid-Based Nanocarriers for Ovarian Cancer Therapy

Repositioning amiodarone, an antiarrhythmic agent, for cancer therapy has garnered increasing interest due to its inhibitory effects on carnitine palmitoyltransferase 1A (CPT1A), a key enzyme upregulated in ovarian cancer (OC)¹. OC is particularly aggressive and prone to peritoneal metastasis, with a metabolic profile characterized by elevated fatty acid oxidation driven by CPT1A overexpression. Despite its therapeutic potential, the clinical application of amiodarone in oncology is hindered by its systemic toxicity. To address this limitation, drug delivery systems (DDSs) offer a promising strategy, with liposomes emerging as an ideal candidate due to their high biocompatibility and tumor-targeting capabilities. Liposomes can exploit the Enhanced Permeability and Retention (EPR) effect or be surface-modified to enhance receptor-mediated targeting, thereby improving drug accumulation and pharmacokinetics². The production method of liposomes critically influences their physicochemical properties, with conventional techniques often requiring post-processing steps to achieve clinical-grade formulations. Microfluidics has recently gained attention as a scalable and precise alternative, offering fine control over parameters such as vesicle size, lamellarity, and distribution³. Using a microfluidic approach, amiodarone was successfully encapsulated into liposomes, with simultaneous generation of amiodarone-containing lipidic particles. Optimization of process parameters, including temperature and flow rate ratio, enabled the production of a stable, uniform DDS. Both formulations were extensively characterized and demonstrated significant efficacy in in vitro models of ovarian cancer, underscoring their potential for further development in targeted cancer therapy⁴.

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[3] Carugo D., Bottaro E., Owen J., Stride E., Nastruzzi, C. 2016, Scientific Reports, 6, 25876.

[4] Saorin A., Saorin G., Duzagac F., Parisse P., Cao N., Corona G., Cavarzerani E., Rizzolio F. 2024, Scientific Reports, 14, 6280.