Quantification and Engineering of Lipid Nanocapsule Formulations for the Delivery of Niclosamide as an Anti-Cancer Drug


Demirtaş H., Tok K. C., Gümüştaş M., Şengel Türk C. T.

CURRENT PHARMACEUTICAL DESIGN, 2025 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2025
  • Doi Numarası: 10.2174/0113816128385620250829061535
  • Dergi Adı: CURRENT PHARMACEUTICAL DESIGN
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: Box-Behnken design, HPLC, lipid nanocapsules, Niclosamide, optimization, validation
  • Ankara Üniversitesi Adresli: Evet

Özet

Introduction Recent studies indicate that niclosamide demonstrates considerable promise as both an anthelmintic agent and a possible anticancer medication. Given the increasing interest in nano-sized drug delivery methods for cancer therapy, lipid nanocapsules (LNCs) have emerged as a viable approach to enhance the bioavailability of poorly soluble pharmaceuticals due to their beneficial properties. This research intends to develop niclosamide-loaded lipid nanocapsules (NIC-LNCs) using the phase inversion technique, followed by the optimization of these formulations via the Box-Behnken experimental design. Methods A reverse-phase high-performance liquid chromatography (RP-HPLC) method was devised and validated for quantifying niclosamide in the LNC formulations. Optimal chromatographic separation was attained utilizing an Agilent Eclipse XDB-C18 column (150x4.6 mm, 5 mu m i.d.) with a mobile phase of a 50:50 (v/v) mixture of acetonitrile and 0.1% H3PO4 phosphate buffer, at a flow rate of 1.2 mL/min. The detection wavelength was set at 335 nm, and the analysis was performed at 35 degrees C. The developed analytical methodology was validated through a comprehensive evaluation of accuracy, linearity, precision, limit of detection, limit of quantitation, specificity, and stability. Results The optimization of the NIC-LNC formulation through the Box-Behnken design resulted in an optimal formulation labeled LNC5, consisting of 4% niclosamide, 20% lipid, and 20% surfactant. The proven RP-HPLC method enables accurate quantification of NIC in the LNC formulations. The refined NIC-LNC formulation exhibited developed attributes as assessed by the design. Discussion NIC-LNCs were successfully prepared with particle sizes below 100 nm, narrow size distributions (PDI<0.2), and negative zeta potential values in accordance with the literature. All formulations exhibited high encapsulation efficiency and sustained drug release profiles. The optimum formulation revealed a particle size of 43.29 +/- 0.32 nm, encapsulation efficiency of 99.99 +/- 0.02%, and drug release at one week of 68.85 +/- 1.76%. The formulation maintained stability throughout the short-term study period.Conclusion The findings indicate that LNC systems are a promising method for drug administration, especially for anticancer drugs with limited solubility in water.