Preparation, characterization, and cytotoxicity evaluation of self-assembled nanoparticles of diosgenin-cytarabine conjugate.

Diosgenin (DG) isolated from yam roots revealed various bioactivities and applications as drug carrier. In the present study, a conjugate of DG with cytarabine (Ara-C) was used to prepare the self-assembled nanoparticles (NPs) of DG-Ara-C by a nanoprecipitation method. Dynamic light scattering (DLS) as well as transmission electron microscopy (TEM) were employed to analyze the size and the morphology of NPs, respectively. The stability and absorption of DG-Ara-C NPs were measured. Additionally, the cytotoxicity of the NPs was determined via MTT assay. The results indicated that the average particle size of DG-Ara-C NPs was around 190 nm with a narrow size distribution (PDI = 0.1). TEM showed that DG-Ara-C NPs had a spherical morphology. Compared to free DG or Ara-C, the self-assembled DG-Ara-C NPs exhibited a better anti-tumor activity against solid tumor cells as well as leukemia cells. In conclusion, DG possesses dual role in the self-assembled NPs of DG-Ara-C conjugate, being as a promising anticancer drug and drug carrier.

Synthesis, anticancer activity and potential application of diosgenin modified cancer chemotherapeutic agent cytarabine.

Diosgenin (DG), a steroidal saponin, is mainly found in yam tubers. DG and its derivatives displayed significant pharmacological activities against inflammatory, hyperlipidemia, and various cancers. DG was selected to modify the cancer chemotherapeutic agent cytarabine (Ara-C) due to its anti-tumor activities as well as lipophilicity. After characterization, the biomembrane affinity and the kinetic thermal processes of the obtained DG-Ara-C conjugate were evaluated by differential scanning calorimetry (DSC). Thin hydration method with sonication was applied to prepare the DG-Ara-C liposomes without cholesterol since the DG moiety has the similar basic structure with cholesterol with more advantages. Dynamic Light Scattering (DLS) analysis and cytotoxic analysis were employed to characterize the DG-Ara-C liposomes and investigate their biological activities, respectively. The results indicated that DG changed the biomembrane affinity of Ara-C and successfully replaced the cholesterol during the liposome preparation. The DG-Ara-C liposomes have an average particle size of around 116 nm with a narrow size distribution and revealed better anti-cancer activity against leukemia cells and solid tumor cells than that of free DG or Ara-C. Therefore, it can be concluded that DG displayed the potential application as an anti-cancer drug carrier to improve the bio-activities, since DG counted for a critical component in modulating the biomembrane affinity, preparation of liposome, and release of hydrophilic Ara-C from lipid vesicles.

Design, synthesis of methotrexate-diosgenin conjugates and biological evaluation of their effect on methotrexate transport-resistant cells.

A series of methotrexate-diosgenin conjugates was designed and synthesized to enhance the passive internalization of methotrexate (MTX) into transport-resistant cells. The inhibitory effects of these conjugates on dihydrofolate reductase (DHFR), and their anti-proliferation behaviors against a transport-resistant breast cancer cell line, MDA-MB-231, were investigated. All of the synthesized conjugates retained an ability to inhibit DHFR after the diosgenin substitution. The MTX conjugates were much more potent against methotrexate-resistant MDA-MB-231 cells than MTX. Conjugate 18, containing a disulfide bond, exhibited the most potent anti-proliferative and DHFR inhibitory effects (IC50=4.1µM and 17.21nM, respectively). Anti-proliferative activity was higher in the conjugate with a longer space linker (conjugate 21) than those with shorter linkers (conjugates 19 and 20). These results suggest that diosgenin conjugation of MTX may be an effective way to overcome its transport resistance in cancer cells.

Behavior of Osteoblast-Like Cells on a ß-Tricalcium Phosphate Synthetic Scaffold Coated With Calcium Phosphate and Magnesium.

OBJECTIVES: Tricalcium phosphate (TCP) is one of the most useful synthetic scaffolds for bone grafts and has several advantages. However, the rapid degradation of TCP makes it less osteoconductive than the other candidates, and represents a major shortcoming. To overcome this problem, the authors investigated magnesium (Mg) and/or hydroxyapatite (HA) coating on a ß-TCP substrate using a sputtering technique. METHODS: Biocompatibility tests were carried out on ß-TCP discs that were either uncoated (TCP), coated with HA by radio frequency magnetron sputtering (HA-TCP), coated with Mg by DC sputtering (Mg-TCP), or multicoated with Mg and HA by DC and radio frequency magnetron sputtering (MgHA-TCP). RESULTS: Cells showed similar morphology in all 4 groups, and were widely spread, had flattened elongated shapes, and were connected to adjacent cells by pseudopods. An MTT assay revealed higher cell proliferation on HA-TCP, Mg-TCP, and MgHA-TCP compared with TCP at 3 and 5 days. MgHA-TCP also showed significantly higher alkaline phosphatase activity levels compared with TCP, HA-TCP, and Mg-TCP (P < 0.05). CONCLUSIONS: Results suggest that Mg-coated ß-TCP could have great potential as a bone graft material for future applications in hard tissue regeneration.

Hydroxyapatite coatings on nanotubular titanium dioxide thin films prepared by radio frequency magnetron sputtering.

In this study, hydroxyapatite (HA) was coated on anodized titanium (Ti) surfaces through radio frequency magnetron sputtering in order to improve biological response of the titanium surface. All the samples were blasted with resorbable blasting media (RBM). RBM-blasted Ti surface, anodized Ti surface, as-sputtered HA coating on the anodized Ti surface, and heat-treated HA coating on the anodized Ti surface were prepared. The samples were characterized using scanning electron microscopy and X-ray photoemission spectroscopy, and biologic responses were evaluated. The top of the TiO2 nanotubes was not closed by HA particles when the coating time is less than 15 minutes. It was demonstrated that the heat-treated HA was well-crystallized and this enhanced the cell attachment of the anodized Ti surface.

Response of fetal rat calvarial cells to nanotubular titanium oxide surface.

This study examined the cell response to a TiO2 nanotubular surface (Ti-NT) for future biomedical applications. The level of cell attachment and spreading at 20 min and 60 min was evaluated by SEM. IL-6 and PGE2 secretion was evaluated by ELISA. In SEM analysis, the Ti-NT surface had more fully spread cells compared to the machined titanium surface (Ti-S). ELISA revealed that the level of IL-6 and PGE2 production was higher on the Ti-NT than on the Ti-S. These results suggest that a surface treatment with a nanotubular TiO2 surface enhances the early osteoblast responses, such as cell spreading and cytokine release, which are important for subsequent cell functions and bone healing in vivo.

The effect of low fresh gas flow rate on sevoflurane consumption.

BACKGROUND: In an era of medical cost containment, cost-effectiveness has become a major focus in healthcare. The effect of a new policy on the use of low fresh gas flow during maintenance of general anesthesia with volatile anesthetics was evaluated. METHODS: The numbers and duration of general anesthesia cases using sevoflurane 5 weeks prior to and 15 weeks after policy implementation were retrieved from the electronic medical records database. The number of sevoflurane bottles consumed was also assessed. The anesthesia hours per bottle of sevoflurane were compared before and after policy implementation. RESULTS: The number of anesthesia hours performed per bottle of sevoflurane increased by 38.3%. The effect varied over time and tended to fade with time. CONCLUSIONS: The implementation of a low fresh gas flow rate policy effectively reduces the amount of sevoflurane consumed for the same duration of anesthesia.