ABSTRACT
To improve its poor aqueous solubility and stability, the potential chemopreventive agent quercetin was encapsulated in freeze-dried polymeric micelles by a thin film hydration and vacuum freeze-drying process before being used for glioma chemotherapy. The micelle characteristics, release profile, cellular uptake, intracellular drug concentration, transport across the blood-brain barrier, and antitumor efficiency in vivo were investigated. Results showed that the particle size of quercetin-loaded freeze-dried nanomicelles (QUE-FD-NMs) ranged from 20 to 80nm, with an efficiently sustained release profile. Increased intracellular uptake into Caco-2 cells with low cytotoxicity, efficient penetration of BBB, and powerful cytotoxicity on C6 glioma cells were observed. QUE-FD-NMs accumulated in tumor-bearing brain tissues and exhibited significant antitumor effects in vivo, which significantly benefited the survival of glioma-bearing mice. These findings suggest that freeze-drying micelles loaded with quercetin is a promising drug delivery method for glioma therapy.
Subject(s)
Antineoplastic Agents/administration & dosage , Brain Neoplasms/drug therapy , Glioma/drug therapy , Micelles , Nanoparticles/administration & dosage , Quercetin/administration & dosage , Animals , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Blood-Brain Barrier/metabolism , Brain Neoplasms/pathology , Cell Line, Tumor , Cell Survival/drug effects , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/pharmacology , Drug Delivery Systems , Drug Liberation , Freeze Drying , Glioma/pathology , Humans , Intestinal Absorption/drug effects , Mice, Inbred BALB C , Mice, Nude , Nanoparticles/therapeutic use , Quercetin/pharmacokinetics , Quercetin/pharmacology , Quercetin/therapeutic use , Tumor Burden/drug effectsABSTRACT
Two kinds of inorganic/organic hybrid composites based on mesoporous silica nanotubes (MSNTs) and pH-responsive polyelectrolytes have been developed as pH-controlled drug delivery systems via the layer by layer self-assembly technique. One system was based on alternatively loading poly(allylamine hydrochloride) and sodium poly(styrene sulfonate) onto as-prepared MSNTs to load and release the positively charged drug doxorubicin. The other system was synthesized by alternately coating sodium alginate and chitosan onto amine-functionalized MSNTs, which were used as vehicles for the loading and release of the negatively charged model drug sodium fluorescein. Controlled release of the drug molecules from these delivery systems was achieved by changing the pH value of the release medium. The results of in vitro cell cytotoxicity assays indicated that the cell killing efficacy of the loaded doxorubicin against human fibrosarcoma (HT-1080) and human breast adenocarcinoma (MCF-7) cells was pH dependent. Thus, these hybrid composites could be potentially applicable as pH-controlled drug delivery systems.
Subject(s)
Coated Materials, Biocompatible/pharmacology , Delayed-Action Preparations/pharmacology , Electrolytes/chemistry , Nanotubes/chemistry , Silicon Dioxide/chemistry , Adsorption/drug effects , Cell Line, Tumor , Doxorubicin/pharmacology , Fluorescein/pharmacology , Humans , Hydrogen-Ion Concentration/drug effects , Microscopy, Confocal , Nanotubes/ultrastructure , Nitrogen , Porosity/drug effects , Spectroscopy, Fourier Transform Infrared , TemperatureABSTRACT
In vitro and in vivo antibacterial activities on the Staphylococcus aureus and Escherichia coli of the amorphous cefuroxime axetil (CFA) ultrafine particles prepared by HGAP method were investigated in this paper. The conventional sprayed CFA particles were studied as the control group. XRD, SEM, BET tests were performed to investigate the morphology changes of the samples before and after sterile. The in vitro dissolution test, minimal inhibitory concentrations (MIC) and the in vivo experiment on mice were explored. The results demonstrated that: (i) The structure, morphology and amorphous form of the particles could be affected during steam sterile process; (ii) CFA particles with different morphologies showed varied antibacterial activities; and (iii) the in vitro and in vivo antibacterial activities of the ultrafine particles prepared by HGAP is markedly stronger than that of the conventional sprayed amorphous particles.
Subject(s)
Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/therapeutic use , Cefuroxime/analogs & derivatives , Escherichia coli Infections/drug therapy , Staphylococcal Infections/drug therapy , Animals , Anti-Bacterial Agents/pharmacology , Cefuroxime/analysis , Cefuroxime/pharmacology , Cefuroxime/therapeutic use , Chemical Precipitation , Drug Compounding , Escherichia coli/drug effects , Mice , Mice, Inbred ICR , Particle Size , Solubility , Staphylococcus aureus/drug effects , X-Ray DiffractionABSTRACT
It has been reported that tetrandrine induces cell cycle arrest and apoptosis in human cancer cells. In the present study, we investigated the role of PI3K/AKT/GSK3beta pathway in tetrandrine- induced G(1) arrest and apoptosis. In HT-29 cells, tetrandrine induced dephosphorylation of AKT, activation and nuclear translocation of GSK3beta as well as upregulation of p27(kip1). Activation of GSK3beta via AKT inhibitoion induced by tetrandrine resulted in enhanced phosphorylation and proteolysis of cyclin D(1), activation of caspase 3 and subsequent cleavage of PARP. Selective GSK3beta inhibitiors and GSK3beta siRNA attenuated tetrandrine-induced G(1) arrest and apoptosis. Similar to tetrandrine, transfection of wild-type GSK3beta led to G(1) arrest and apoptosis via downregulation of cyclin D(1) and cleavage of PARP. These findings suggest that tetrandrine induces G(1) arrest and apoptosis through PI3K/AKT/GSK3beta pathway and identify GSK3beta as an important mediator in the processes.
