Niclosamide is an anthelmintic drug that also demonstrates great potential in fighting against cancers. However, parenteral delivery of niclosamide is challenged due to its insoluble property. This study aimed to develop an injectable formulation for niclosamide using nanocrystals. Niclosamide nanocrystals were prepared by wet media milling technique and characterized by electronic microscopes, differential scanning calorimetry, powder X-ray diffractometry and drug release, etc. The resulting nanocrystals using Tween 80 as the stabilizer were approximately 235 nm in particle size and showed a satisfactory stability. Pharmacokinetic studies revealed that there was no significant difference in plasma concentration-time profiles between nanocrystals and the control formulation (i.e. drug solution). By contrast, a significant difference in tissue distribution was observed at 2 h. Further, niclosamide nanocrystals presented a comparable antitumor effect to the drug solution against EC9076 cell line. We concluded that the nanocrystal formulation with solution-like behaviors should be a promising choice for intravenous delivery of niclosamide.
Niclosamide (NIC) has been found to have outstanding antitumour activity in recent years, but its clinical application has been limited by its poor water solubility. In this study, nanomicelles (PEG 2K -Fmoc-Ibuprofen micelles , PEG 2K -FIbu) were prepared as carriers to improve the solubility and bioavailability of NIC. Nuclear magnetic resonance (NMR) confirmed its successful preparation. The drug-carrying micelles (PEG 2K -FIbu/NIC) were then prepared using a thin film dispersion method. PEG 2K -FIbu and PEG 2K -FIbu/NIC were analysed in detail in terms of particle size, polymer dispersion index, stability and encapsulation efficiency. Finally, the in vivo effects of PEG 2K -FIbu/NIC were tested in a mouse liver cancer model. The particle size of PEG 2K -FIbu was 11.11 nm. The encapsulation rate was 70.4% and the tumour inhibition rate was 55.98%. Tumours were significantly reduced and damage to the liver was greatly reduced. The histopathological sections and serum biochemical indices also showed that the symptoms were significantly improved after administration. In summary, PEG 2K -FIbu/NIC is a potential drug delivery system of NIC to effectively treat liver cancer, providing an effective dosage form for NIC.
危险品化学品经营许可证（带存储）