ABSTRACT
The aim of this study is to prepare ciprofloxacin (CIP) or levofloxacin (LEVO)-incorporated and polydopamine (PDA)-coated nephrite composites for application in drug-eluting contact lenses. PDA was coated onto the surface of nephrite to improve antibacterial activity and to payload antibiotics. CIP or LEVO was incorporated into the PDA layer on the surface of nephrite. Furthermore, CIP-incorporated/PDA-coated nephrite composites were embedded into the contact lenses. PDA-coated nephrite composites showed dull and smooth surfaces according to the dopamine concentration while nephrite itself has sharp surface morphology. CIP- or LEVO-loaded/PDA-coated nephrite composites also have dull and smooth surface properties. Nano and/or sub-micron clusters were observed in field emission-scanning electron microscopy (FE-SEM) observation, indicating that PDA nanoparticles were accumulated and coated onto the surface of nephrite. Furthermore, CIP- or LEVO-incorporated/PDA-coated nephrite composites showed the sustained release of CIP or LEVO in vitro and these properties contributed to the enhanced antibacterial activity of composites compared to nephrite or PDA-coated nephrite composites. CIP-incorporated/PDA-coated nephrite composites were embedded in the contact lenses and then, in an antibacterial study, they showed higher bactericidal effect against Staphylococcus aureus (S. aureus) compared to nephrite itself or PDA-coated nephrite composites. We suggest that CIP- or LEVO-loaded/PDA-coated nephrite composite-embedded contact lenses are a promising candidate for therapeutic application.
ABSTRACT
Novel phytosphingosine derivatives have been developed based on the inhibition of sphingosine kinase, which has been implicated in cell growth and inhibition of ceramide-mediated apoptosis. This study evaluated the cytotoxic effects and underlying mechanisms of action of novel phytosphingosine derivatives, including N-monomethylphytosphingosine (MMPH) and N,N-dimethylphytosphingosine (DMPH) and the pegylated forms MMPH-PEG and DMPH-PEG, in human leukemia HL60 cells. In viability and proliferation assays using WST-1, all four drugs induced suppression of cell growth and viability in a concentration-dependent manner. Among them, DMPH had the highest antileukemic activity and induced apoptosis via caspase-8, caspase-3, and caspase-9 activation. The apoptotic effect was also associated with Fas/FasL upregulation, Bid cleavage, Bcl-2 downregulation, Bax upregulation, mitochondrial membrane depolarization, and cytochrome c release. DMPH decreased the phosphorylation of ERK and inhibited daunorubicin-induced ERK activation. Furthermore, DMPH displayed synergistic cytotoxicity with daunorubicin in a sequence-dependent manner. Our findings indicate that DMPH has potential as an effective cytotoxic agent for leukemia.
