curcumin and coumarin-6

Liquid lipid nanocapsules (LLN) represent a promising new generation of drug-delivery systems. They can carry hydrophobic drugs in their oily core, but the composition and structure of the surrounding protective shell determine their capacity to survive in the circulatory system and to achieve their goal: penetrate tumor cells. Here, we present a study of LLN covered by the protein human serum albumin (HSA) and loaded with curcumin as a hydrophobic model drug. A cross-linking procedure was performed to further strengthen the protective protein layer. Physicochemical properties and release kinetics of the nanocapsules were investigated, and cellular uptake and killing capacity were evaluated on the human breast-cancer line MCF-7. The nanocapsules exhibited a half maximal inhibitory concentration (IC

Topics: Breast Neoplasms; Cell Proliferation; Cell Survival; Coumarins; Curcumin; Drug Liberation; Endocytosis; Female; Humans; Lipids; MCF-7 Cells; Nanocapsules; Serum Albumin; Thiazoles

Nanoparticles (NPs) modified with bio-ligands represent a promising strategy for active targeted drug delivery to tumour. However, many targeted ligands, such as trastuzumab (TMAB), have high molecular weight, limiting their application for targeting. In this study, we prepared Fab' (antigen-binding fragments cut from TMAB)-modified NPs (Fab'-NPs) with curcumin (Cur) as a model drug for more effective targeting of human epidermal growth factor receptor 2 (HER2/ErbB2/Neu), which is overexpressed on breast cancer cells.. The release kinetics was conducted by dialysis bags. The ability to kill HER2-overexpressing BT-474 cells of Fab'-Cur-NPs compared with TMAB-Cur-NPs was conducted by cytotoxicity experiments. Qualitative and quantitative cell uptake studies using coumarin-6 (fluorescent probe)-loaded NPs were performed by fluorescence microscopy and flow cytometry. Pharmacokinetics and biodistribution experiments in vivo were assessed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).. The release kinetics showed that both Fab'-Cur-NPs and TMAB-Cur-NPs provided continuous, slow release of curcumin for 72 h, with no significant difference. In vitro cytotoxicity experiments showed that Fab'-Cur-NPs manifested prominent ability to kill HER2-overexpressing BT-474 cells compared with TMAB-Cur-NPs. Qualitative and quantitative cell uptake studies indicated that the accumulation of Fab'-NPs was greater than that of TMAB-NPs in BT-474 (HER2+) cells; However, there was no significant difference in MDA-MB-231 (HER2-) cells. Pharmacokinetics and biodistribution experiments in vivo demonstrated that the half-life (t1/2) and area under the blood concentration-time curve (AUC0-t) of Fab'-Cur-NPs increased 5.30-fold and 1.76-fold relative to those of TMAB-Cur-NPs, respectively. Furthermore, the tumor accumulation of Fab'-Cur-NPs was higher than that of TMAB-Cur-NPs.. Fab' fragment has greater capacity than the intact antibody to achieve tumor targeting through NP-based delivery.

Topics: Animals; Cell Death; Cell Line, Tumor; Coumarins; Curcumin; Endocytosis; Female; Flow Cytometry; Humans; Immunoglobulin Fab Fragments; Injections, Intravenous; Mice, Inbred BALB C; Microscopy, Fluorescence; Nanoparticles; Polyesters; Polyethylene Glycols; Rats, Sprague-Dawley; Thiazoles; Tissue Distribution; Trastuzumab

Combination therapy is increasingly used as a primary cancer treatment regimen. In this report, we designed EGFR peptide decorated nanoparticles (NPs) to co-deliver docetaxel (DTX) and pH sensitive curcumin (CUR) prodrug for the treatment of prostate cancer.. EGFR peptide (GE11) targeted, pH sensitive, DTX and CUR prodrug NPs (GE11-DTX-CUR NPs) had an average diameter of 167nm and a zeta potential of -37.5mV. The particle size of the NPs was adequately maintained in serum and a sustained drug release pattern was observed. Improved inhibition of cancer cell and tumor tissue growth was shown in the GE11-DTX-CUR NPs group compared to the other groups.. It can be summarized that DTX and CUR prodrug could be delivered into tumor cells simultaneously by the GE 11 targeting and the EPR effect of NPs. The resulting GE11-DTX-CUR NPs is a promising system for the synergistic antitumor treatment of prostate cancer.

Topics: Aconitic Acid; Animals; Antineoplastic Agents; Cell Death; Cell Line, Tumor; Coumarins; Curcumin; Docetaxel; Drug Delivery Systems; Drug Liberation; Drug Stability; Drug Synergism; Endocytosis; Humans; Inhibitory Concentration 50; Lactic Acid; Male; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Particle Size; Peptides; Polyethylene Glycols; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Prodrugs; Prostatic Neoplasms; Proton Magnetic Resonance Spectroscopy; Taxoids; Thiazoles