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Background: Avicequinone-B (Naphtho[2,3-b]furan-4,9-dione) is a furanonaphthoquinone derivative. It is a hydrophobic compound with poor aqueous solubility, which may restrict its potential pharmaceutical and biomedical applications., Purpose: We synthesized different liposomal formulations of Avicequinone-B, and measured their particle size, aqueous solubility, and physicochemical properties. In addition, we investigated the anticancer activity of liposomal Avicequinone-B in human cutaneous squamous cell carcinoma (SCC) cells., Methods: Liposomal Avicequinone-B formulations were synthesized using the thin-film hydration method. Drug yield, encapsulation efficiency and aqueous solubility were determined by high performance liquid chromatography. Particle size and polydispersity index were measured by submicron particle size analyzer, and ultrastructural morphology was visualized by transmission electron microscopy. Thermal transitions were determined by differential scanning calorimetry. Anti-skin cancer activity was determined in HSC-1 cells (human cutaneous SCC cell line) using the MTS cytotoxicity assay, apoptosis was assessed by caspase-3/7 activity assay, mitochondrial membrane potential was determined by JC-10 assay, and signal transduction pathways were evaluated by Western blot analysis., Results: Liposomal Avicequinone-B formulations showed adequate yield and high encapsulation efficiency. These liposomal formulations produced small, uniformly sized nanoparticles, and greatly increased the aqueous solubility of Avicequinone-B. Differential scanning calorimetry showed loss of thermal phase transitions. In addition, liposomal Avicequinone-B showed significant cytotoxic effect on HSC-1 cells, through reduction of mitochondrial membrane potential, increased cytosolic cytochrome-c level, increased cleaved caspase 8 level, and induction of apoptosis. This was mediated through activation of ERK, p38 and JNK signaling pathways., Conclusion: Liposomal Avicequinone-B demonstrated improved aqueous solubility and physicochemical characteristics, and induced apoptosis in cutaneous SCC cells. Therefore, liposomal Avicequinone-B may have potential uses as a topical anti-skin cancer drug formulation in the future., (Copyright © 2019. Published by Elsevier GmbH.)

Background: Saikosaponin-d (SSD) is a triterpene saponin isolated from Bupleurum plants. It has been shown to exhibit antioxidant, anti-inflammatory, and anticancer activities. However, its biomedical applications are limited by its poor water solubility. Cyclodextrins are highly water soluble oligosaccharide compounds which can form inclusion complexes with lipophilic drugs., Purpose: We complexed SSD with hydroxypropyl-β-cyclodextrin (HPBCD) in various ratios to form SSD-HPBCD inclusion complexes. The inclusion complexes were evaluated for their solubility, physicochemical properties and cytotoxic effects in cutaneous squamous cell carcinoma cells., Methods: Surface morphology of pure SSD and SSD-HPBCD inclusion complexes was evaluated by scanning electron microscopy. Crystalline structure was determined by X-ray diffractometry. Intermolecular hydrogen bond formation between SSD and HPBCD was investigated by Fourier transform infrared spectroscopy. Human cutaneous squamous cell carcinoma HSC-1 cell viability was determined by the MTS assay, and cell apoptosis by the caspase 3/7 assay. Signal transduction pathways were investigated by Western blotting., Results: SSD-HPBCD inclusion complexes showed greatly increased water solubility. This was associated with an improvement in physicochemical properties, including transformation of crystalline structure to amorphous form, and formation of hydrogen bonds between SSD and HPBCD. In addition, SSD-HPBCD inclusion complexes induced apoptosis in HSC-1 cells, and this was mediated through activation of MAPK and suppression of Akt-mTOR signaling pathways., Conclusion: SSD-HPBCD inclusion complex shows improvement in water solubility and physicochemical properties, and exhibits anticancer effects against cutaneous squamous cell carcinoma cells. Therefore, it may be a potential drug formulation for the treatment of skin cancer., (Copyright © 2018. Published by Elsevier GmbH.)

Background: Hepatocellular carcinoma (HCC) is the most common liver cancer worldwide, with poor prognosis and resistance to chemotherapy. This gives novel cancer treatment methods an overwhelming significance. Natural products offer great resources of developing new and effective chemopreventive or chemotherapeutic agents. Artocarpus communis extracts and its active constituent, prenylated flavonoid artocarpin induce human hepatocellular carcinoma cell death. However, the poor water solubility drawbacks of artocarpin restrict its clinical application and bioavailability., Purpose: This study developed the artocarpin nanoparticle system to overcome the poor water solubility drawbacks and investigated the improvement of therapeutic efficacy of artocarpin by adopting novel nanoparticle delivery strategy., Methods: Antiproliferative activity of artocarpin was evaluated by MTT assay. Cell morphology observation by microscope, DNA fragmentation assay, cell cycle analysis, Annexin V apoptosis cell staining, monodansylcadaverine and acridine orange staining and immunoblot analysis were used to evaluate the induction of autophagy by artocarpin. The determination of particle size, amorphous transformation, hydrogen-bond formation, yield, encapsulation efficiency and the solubility study were used to investigate the solubility enhancement mechanism of artocarpin., Results: The present study demonstrates that the anticancer effect of artocarpin in HepG2 and PLC/PRF/5 hepatoma cells is mediated through the autophagic cell death mechanism. Results also demonstrated that artocarpin nanoparticles enhanced the solubility of artocarpin by reducing particle size, transforming high energy amorphous state, and forming hydrogen bond with excipients. Additionally, ArtN exhibited better autophagic cytotoxicity compared to free artocarpin., Conclusion: This work reveals the antihepatoma activity of artocarpin by inducing autophagic cell death and the improvement of therapeutic efficacy of artocarpin by adopting novel nanoparticle delivery strategy. The research provided a basis of ArtN could be explored as a low-dose alternative of artocarpin in anticancer treatment and research applications., (Copyright © 2016 Elsevier GmbH. All rights reserved.)