Preparation and characterization of norcantharidin liposomes modified with stearyl glycyrrhetinate

In the current study, norcantharidin (NCTD)-loaded liposomes (LIPs) modified with stearyl glycyrrhetinate (SG; SG-NCTD-LIP) were prepared by the ethanol injection method. To increase the drug encapsulation efficiency (EE), the formulation of NCTD-LIP was optimized by single factor test and orthogonal design. The release of NCTD in vitro from SG-NCTD-LIP was evaluated by equilibrium dialysis. The cytotoxicity of SG-NCTD-LIP in HepG2 was investigated by MTT assay. The results revealed that the EE of liposomes was ~27.80%, the average SG-NCTD-LIP was 87.5 nm, the in vitro NCTD release from SG-NCTD-LIP was delayed compared with NCTD in solution and the drug-release kinetic followed a first-order model. MTT assays revealed increased cytotoxicity activity against HepG2 cells for SG-NCTD-LIP compared with free NCTD. In conclusion, SG-NCTD-LIP prepared in the present study may be a promising liposomal drug delivery system for anticancer drugs in liver-targeting therapy.

[1]  S. Bashir,et al.  Liposomal co-delivered oleanolic acid attenuates doxorubicin-induced multi-organ toxicity in hepatocellular carcinoma , 2017, Oncotarget.

[2]  Ram I Mahato,et al.  Recent advances in hepatocellular carcinoma therapy. , 2017, Pharmacology & therapeutics.

[3]  Dong Liu,et al.  Preparation and in vivo safety evaluations of antileukemic homoharringtonine-loaded PEGylated liposomes , 2017, Drug development and industrial pharmacy.

[4]  M. Fan,et al.  Norcantharidin-induced Apoptosis of AGS Human Gastric Cancer Cells Through Reactive Oxygen Species Production, and Caspase- and Mitochondria-dependent Signaling Pathways. , 2016, Anticancer research.

[5]  F. Dorkoosh,et al.  Hyaluronic acid-coated liposomes for targeted delivery of paclitaxel, in-vitro characterization and in-vivo evaluation. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[6]  Jianqing Gao,et al.  Folate receptor-targeted liposomes loaded with a diacid metabolite of norcantharidin enhance antitumor potency for H22 hepatocellular carcinoma both in vitro and in vivo , 2016, International journal of nanomedicine.

[7]  D. Yan,et al.  Amphiphilic nanoparticles of resveratrol-norcantharidin to enhance the toxicity in zebrafish embryo. , 2016, Bioorganic & medicinal chemistry letters.

[8]  A. Abbasi,et al.  Optimizing the therapeutic efficacy of cisplatin PEGylated liposomes via incorporation of different DPPG ratios: In vitro and in vivo studies. , 2015, Colloids and surfaces. B, Biointerfaces.

[9]  Xiangcheng Li,et al.  Atg5 siRNA inhibits autophagy and enhances norcantharidin-induced apoptosis in hepatocellular carcinoma. , 2015, International journal of oncology.

[10]  In‐San Kim,et al.  Enhanced delivery of liposomes to lung tumor through targeting interleukin-4 receptor on both tumor cells and tumor endothelial cells. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[11]  Yitao Wang,et al.  Glycyrrhetinic Acid-Mediated Polymeric Drug Delivery Targeting the Acidic Microenvironment of Hepatocellular Carcinoma , 2015, Pharmaceutical Research.

[12]  Yong Gao,et al.  A novel glycyrrhetinic acid-modified oxaliplatin liposome for liver-targeting and in vitro/vivo evaluation , 2015, Drug design, development and therapy.

[13]  Yaping Zhang,et al.  Norcantharidin inhibits Wnt signal pathway via promoter demethylation of WIF-1 in human non-small cell lung cancer , 2015, Medical Oncology.

[14]  F. Atyabi,et al.  Enhanced Cellular Cytotoxicity and Antibacterial Activity of 18-β-Glycyrrhetinic Acid by Albumin-conjugated PLGA Nanoparticles , 2015, Drug Research.

[15]  Jin-jian Lu,et al.  Glycyrrhetinic Acid Triggers a Protective Autophagy by Activation of Extracellular Regulated Protein Kinases in Hepatocellular Carcinoma Cells , 2014, Journal of agricultural and food chemistry.

[16]  H. Harashima,et al.  An aptamer ligand based liposomal nanocarrier system that targets tumor endothelial cells. , 2014, Biomaterials.

[17]  Yong Wang,et al.  Synthesis of Glycyrrhetinic Acid-Modified Chitosan 5-Fluorouracil Nanoparticles and Its Inhibition of Liver Cancer Characteristics in Vitro and in Vivo , 2013, Marine drugs.

[18]  Wenxiu Zhao,et al.  18β‐glycyrrhetinic acid inhibits hepatocellular carcinoma development by reversing hepatic stellate cell‐mediated immunosuppression in mice , 2013, International journal of cancer.

[19]  B. Zhang,et al.  Preclinical evaluations of norcantharidin-loaded intravenous lipid microspheres with low toxicity , 2012, Expert opinion on drug delivery.

[20]  Shuijun Zhang,et al.  Norcantharidin enhances ABT-737-induced apoptosis in hepatocellular carcinoma cells by transcriptional repression of Mcl-1. , 2012, Cellular signalling.

[21]  Ping Wang,et al.  Self-assembly and liver targeting of sulfated chitosan nanoparticles functionalized with glycyrrhetinic acid. , 2012, Nanomedicine : nanotechnology, biology, and medicine.

[22]  T. Roskams,et al.  Glycyrrhizin in patients who failed previous interferon alpha-based therapies: biochemical and histological effects after 52 weeks , 2012, Journal of viral hepatitis.

[23]  X. Ke,et al.  The anti-tumor performance of docetaxel liposomes surface-modified with glycyrrhetinic acid , 2012, Journal of drug targeting.

[24]  Qiang Zhang,et al.  Novel norcantharidin-loaded liver targeting chitosan nanoparticles to enhance intestinal absorption , 2012, 2011 5th International Conference on Bioinformatics and Biomedical Engineering.

[25]  Qiang Zhang,et al.  Pharmacokinetics, tissue distribution, and metabolites of a polyvinylpyrrolidone-coated norcantharidin chitosan nanoparticle formulation in rats and mice, using LC-MS/MS , 2012, International journal of nanomedicine.

[26]  G. Kibria,et al.  Dual-ligand modification of PEGylated liposomes shows better cell selectivity and efficient gene delivery. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[27]  Min Liu,et al.  Glycyrrhetinic acid-modified chitosan/poly(ethylene glycol) nanoparticles for liver-targeted delivery. , 2010, Biomaterials.

[28]  Dmitri A. Ossipov Nanostructured hyaluronic acid-based materials for active delivery to cancer , 2010, Expert opinion on drug delivery.

[29]  Hiroshi Maeda,et al.  Tumor-selective delivery of macromolecular drugs via the EPR effect: background and future prospects. , 2010, Bioconjugate chemistry.

[30]  Weihong Tan,et al.  A liposome-based nanostructure for aptamer directed delivery. , 2010, Chemical communications.

[31]  Qingbing Zeng,et al.  Poly(lactide-co-glycolide) nanoparticles as carriers for norcantharidin , 2009 .

[32]  L. Zhang,et al.  Nanoparticles in Medicine: Therapeutic Applications and Developments , 2008, Clinical pharmacology and therapeutics.

[33]  Shiying Xu,et al.  Preparation of salidroside nano-liposomes by ethanol injection method and in vitro release study , 2008 .

[34]  Dae-Duk Kim,et al.  Preparation and evaluation of paclitaxel-loaded PEGylated immunoliposome. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[35]  Xiao-Li Li,et al.  [Pharmacokinetics and biodistribution of 3H-norcantharidin in mice]. , 2007, Yao xue xue bao = Acta pharmaceutica Sinica.

[36]  S. Safe,et al.  Structure-dependent activity of glycyrrhetinic acid derivatives as peroxisome proliferator–activated receptor γ agonists in colon cancer cells , 2007, Molecular Cancer Therapeutics.

[37]  V. Torchilin Recent advances with liposomes as pharmaceutical carriers , 2005, Nature Reviews Drug Discovery.

[38]  H. Kodama,et al.  Humoral immune response of carp (Cyprinus carpio) induced by oral immunization with liposome-entrapped antigen. , 2003, Developmental and comparative immunology.

[39]  S M Moghimi,et al.  Long-circulating and target-specific nanoparticles: theory to practice. , 2001, Pharmacological reviews.

[40]  A. McCluskey,et al.  Small molecule inhibitors of serine/threonine protein phosphatases. , 2001, Mini reviews in medicinal chemistry.

[41]  A. Ichikawa,et al.  Specific binding of glycyrrhetinic acid to the rat liver membrane. , 1991, Biochimica et biophysica acta.

[42]  G. Gregoriadis,et al.  Effect of the cholesterol content of small unilamellar liposomes on their stability in vivo and in vitro. , 1980, The Biochemical journal.

[43]  A. Bangham,et al.  Diffusion of univalent ions across the lamellae of swollen phospholipids. , 1965, Journal of molecular biology.

[44]  T. Higuchi MECHANISM OF SUSTAINED-ACTION MEDICATION. THEORETICAL ANALYSIS OF RATE OF RELEASE OF SOLID DRUGS DISPERSED IN SOLID MATRICES. , 1963, Journal of pharmaceutical sciences.

[45]  T. Han,et al.  Antimetastatic effects of norcantharidin on hepatocellular carcinoma cells by up-regulating FAM46C expression. , 2017, American journal of translational research.

[46]  H. Pandey,et al.  Liposome and Their Applications in Cancer Therapy , 2016 .

[47]  A. Ichikawa,et al.  Glycyrrhetinic acid bound to 11 beta-hydroxysteroid dehydrogenase in rat liver microsomes. , 1992, Biochimica et Biophysica Acta.

[48]  S. Parlee,et al.  This Work Is Licensed under a Creative Commons Attribution-noncommercial 4.0 International License , 2022 .