3-7-11-15-tetramethyl-1-2-3-hexadecanetriol and Liver-Neoplasms

Transarterial chemoembolization is the preferred treatment for patients with middle and advanced-stage hepatocellular carcinoma (HCC); however, most hepatic artery embolization agents have various disadvantages. The purpose of this study was to evaluate phytantriol-based liquid crystal injections for potential use in treatment of HCC.. Using sinomenine (SN) and 5-fluorouracil (5-FU) as model drugs, three precursor in situ liquid crystal injections based on phytantriol (P1, P2, and P3) were prepared, and their in vitro biocompatibility, anticancer activity, and drug release investigated, to evaluate their feasibility for use in treatment of HCC. The properties of the precursor injections and subsequent cubic liquid crystal gels were observed by visual and polarizing microscopy, in an in vitro gelation experiment. Biocompatibility was evaluated by in vitro hemolysis, histocompatibility, and cytotoxicity assays.. Precursor injections were colorless liquids that formed transparent cubic liquid crystal gels on addition of excess water. The three precursor injections all caused slight hemolysis, without agglutination, and were mildly cytotoxic. Histocompatibility experiments showed that P1 had good histocompatibility, while P2 and P3 resulted in strong inflammatory responses, which subsequently resolved spontaneously. In vitro anti-cancer testing showed that SN and 5-FU inhibited HepG2 cells in a time- and concentration-dependent manner and had synergistic effects. Further, in vitro release assays indicated that all three preparations had sustained release effects, with cumulative release of >80% within 48 h.. These results indicate that SN and 5-FU have synergistic inhibitory effects on HepG2 cells, which has not previously been reported. Moreover, we describe a biocompatible precursor injection, useful as a drug carrier for the treatment of liver cancer, which can achieve targeting, sustained release, synergistic chemotherapy, and embolization. These data indicate that precursor injections containing SN and 5-FU have great potential for use in therapy for liver cancer.

Topics: Animals; Antineoplastic Agents; Carcinoma, Hepatocellular; Cell Death; Drug Carriers; Drug Liberation; Drug Synergism; Fatty Alcohols; Fluorouracil; Gels; Hemolysis; Hep G2 Cells; Humans; Injections; Liquid Crystals; Liver Neoplasms; Morphinans; Rats, Sprague-Dawley; Water

Transcatheter arterial chemoembolization (TACE) is the preferred treatment for patients with advanced hepatocellular carcinoma (HCC), but it lacks safe and effective embolic agents. 5-Fluorouracil (5-FU) is a broad-spectrum anticancer drug, but its clinical application is limited due to drug resistance and toxic side effects. Therefore, in this study, we developed a new liquid embolic agent with 5-FU as the model drug. We found that this liquid embolic agent possesses good gelling properties and embolic effects. An

Topics: Animals; Antineoplastic Agents; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Survival; Chemoembolization, Therapeutic; Drug Delivery Systems; Drug Liberation; Fatty Alcohols; Fluorouracil; Liquid Crystals; Liver Neoplasms; Rabbits; Rats; Rats, Sprague-Dawley

The potential feasibility of using phytantriol-based inverted type bicontinuous cubic phase as an embolization agent and sustained release system was evaluated in this study. In the ternary phytantriol-water-ethanol system, when water content was less than 30% (w/w), the injectable isotropic solution was formed and could transform into the bicontinuous cubic phase upon contacting the dissolution/body fluids. The transformation of the isotropic solution was confirmed by polarized light microscopy (PLM), small angle X-ray scattering (SAXS), resonance Raman spectroscopy, and rheological measurements. The in vitro dissolution results showed that the release was sustained for up to 30 days and was affected by drug loading and the initial compositions of isotropic solutions. In vivo, the embolization study was performed with normal rabbits using transcatheter arterial embolization technique and was monitored under digital subtraction angiography (DSA). The angiographical results showed that the hepatic artery was successfully embolized with phytantriol cubic phase. Therefore, with the vascular embolization and sustained release characteristics, the phytantriol-based inverted type bicontinuous cubic phase could be used for arterial transcatheter chemoembolization on hepatocellular carcinoma.

Topics: Angiography, Digital Subtraction; Animals; Blood Vessels; Carcinoma, Hepatocellular; Delayed-Action Preparations; Drug Delivery Systems; Embolization, Therapeutic; Ethanol; Fatty Alcohols; Liquid Crystals; Liver Neoplasms; Microscopy, Polarization; Phase Transition; Rabbits; Rheology; Scattering, Small Angle; Spectrum Analysis, Raman; Water; X-Ray Diffraction