Enhanced efficacy of functionalized epirubicin liposomes in treating brain glioma-bearing rats.

State Key Laboratory of Natural and Biomimetic Drugs, and School of Pharmaceutical Sciences, Peking University, Beijing, China.
European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences (Impact Factor: 2.61). 10/2010; 41(2):232-43. DOI: 10.1016/j.ejps.2010.06.008
Source: PubMed

ABSTRACT The restriction of drug transporting across the blood-brain barrier (BBB) and the limit of drug penetrating into the tumor tissue remain the major obstacles for brain tumor chemotherapy. In the present study, we developed a functionalized liposomal nanoconstruct, epirubicin liposomes modified with tamoxifen (TAM) and transferrin (TF), for transporting drug across the BBB and afterwards targeting the brain glioma.
Evaluations were performed on the murine C6 glioma cells, the C6 glioma spheroids, the BBB model in vitro and the brain glioma-bearing rats.
When compared with controls, epirubicin liposomes modified with TAM and TF showed the strongest inhibitory effect to C6 glioma cells or glioma spheroids in vitro, significant transport ability across the BBB model in vitro, an evident effect of targeting the brain tumor cells in vitro, and an extended median survival time in the brain glioma-bearing rats.
Epirubicin liposomes modified with TAM and TF significantly improve the therapeutic efficacy of brain glioma in vitro and in animals, hence providing a new strategy for brain tumor chemotherapy.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The poor selectivity of chemotherapeutics for cancer treatment may lead to dose-limiting side effects that compromise clinical outcomes. To solve the problem, surface-functionalized polymer nanoparticles are regarded as promising tumor-targeting delivery system. On the basis of glucose transporter (GLUT) overexpression on cancer cells, d-glucosamine-conjugated and paclitaxel-loaded poly(ethylene glycol)-co-poly(trimethylene carbonate) copolymer nanoparticles (DGlu-NP/PTX) were developed as potential tumor-targeting drug delivery system in this study. Because of the high affinity between d-glucosamine and GLUT, DGlu-NP/PTX could target to tumor tissue through GLUT-mediated endocytosis to improve the selectivity of PTX. DGlu-NP/PTX was prepared by emulsion/solvent evaporation technique and characterized in terms of morphology, size, and zeta potential. In vitro evaluation of two-dimensional cells and three-dimensional tumor spheroids revealed that DGlu-NP/PTX was more potent than those of plain nanoparticles (NP/PTX) and Taxol. In vivo multispectral fluorescent imaging indicated that DGlu-NP had higher specificity and efficiency on subcutaneous xenografts tumor of mouse. Furthermore, DGlu-NP/PTX showed the greatest tumor growth inhibitory effect on in vivo subcutaneous xenografts model with no evident toxicity. Therefore, these results demonstrated that DGlu-NP/PTX could be used as potential vehicle for cancer treatment. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci
    Journal of Pharmaceutical Sciences 03/2014; · 3.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide. Epirubicin (EPI), an anthracycline derivative, is one of the main line treatments for HCC. However, serious side effects including cardiomyopathy and congestive heart failure limit its long term administration. Our main goal is to develop a delivery strategy that ensures improved efficacy of the chemotherapeutic agent together with reduced cardiotoxicity. In this context, EPI was loaded in chitosan-PLGA nanoparticles linked with asialofetuin (EPI-NPs) selectively targeting hepatocytes. In an attempt to reduce cardiotoxicity, targeted EPI-NPs were coadministered with tocotrienols. EPI-NPs significantly enhanced the antiproliferative effect compared to free EPI as studied on Hep G2 cell line. Nanoencapsulated EPI injected in HCC mouse model revealed higher p53-mediated apoptosis and reduced angiogenesis in the tumor. Combined therapy of EPI-NPs with tocotrienols further enhanced apoptosis and reduced VEGF level in a dose dependent manner. Assessment of cardiotoxicity indicated that EPI-NPs diminished the high level of proinflammatory cytokine tumor necrosis factor-α (TNF-α) as well as oxidative stress-induced cardiotoxicity as manifested by reduced level of lipid peroxidation products (TBARS) and nitric oxide (NO). EPI-NPs additionally restored the diminished level of superoxide dismutase (SOD) and reduced glutathione (GSH) in the heart. Interestingly, tocotrienols provided both antitumour activity and higher protection against oxidative stress and inflammation induced by EPI in the heart. This hepatocyte-targeted biodegradable nanoparticle / tocotrienol combined therapy represents intriguing therapeutic strategy for EPI providing not only superior efficacy but also higher safety levels.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 05/2014; · 3.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Nanotechnology has received great attention since a decade for the treatment of different varieties of cancer. However, there is a limited data available on the cytotoxic potential of Temozolomide (TMZ) formulations. In the current research work, an attempt has been made to understand the anti-metastatic effect of the drug after loading into PLGA nanoparticles against C6 glioma cells.Nanoparticles were prepared using solvent diffusion method and were characterized for size and morphology. Diffusion of the drug from the nanoparticles was studied by dialysis method. The designed nanoparticles were also assessed for cellular uptake using confocal microscopy and flow cytometry. PLGA nanoparticles caused a sustained release of the drug and showed a higher cellular uptake. The drug formulations also affected the cellular proliferation and motility. PLGA coated nanoparticles prolong the activity of the loaded drug while retaining the anti-metastatic activity.
    DARU-JOURNAL OF FACULTY OF PHARMACY 01/2014; 22(1):18. · 0.62 Impact Factor