Drug delivery systems for colorectal cancer chemotherapy

Colorectal cancer causes the third most common type of malignant tumors with high morbidity and mortality.Chemotherapy is currently one of the most effective and common treatments for colorectal cancer.However,the poor water solubility of some chemotherapeutics,untargeted drug delivery,and the undesirable systemic side effects of conventional treatment remain the major issues for colorectal cancer chemotherapy.Fortunately,drug delivery systems(DDS)based on biomaterials have been widely investigated and found to be capable of resolving those issues with good performance.Therefore,the main goal of this review is to summarize and discuss the progress and potential advantages of different DDS for colorectal cancer chemotherapy.We not only reviewed the nanocarriers used to improve the solubility of chemotherapeutics,including liposomes,micelles,and nanoparticles,but also discussed targeted DDS based on specific ligand-receptor recognition and tumor microenvironmental stimulus responses.Furthermore,locally administered systems based on hydrogels and microspheres,which have been shown to increase drug accumulation at the tumor site while decreasing systemic toxicity,were also emphasized.DDS provides a good option for improving the efficacy of chemotherapy in the treatment of colorectal cancer.

Potential Antimicrobial Effects of Gatifloxacin on Periodontopathic Bacteria in Vitro

The aim of this study was to identify the potential antibacterial effects of gatifloxacin on periodontal pathogens including Aggregatibacter actinomycetemcomitans, Porphyromonas gingi-valis, and Prevotella intermedia. The minimum inhibitory concentrations (MIC) of gatifloxacin and its bactericidal effects were investigated. Gatifloxacin inhibited the growth of all three kinds of periodontopathic bacteria tested in broth. The MIC value of 2.5 nM was found to be the most effective in inhibiting A. actinomycetemcomitans. An adenosine triphosphate biolumi-nescence assay revealed that gatifloxacin exhibited bactericidal effects on the tested bacteria in a time-dependent manner. The safety of gatifloxacin in mammalian cells was evaluated by assessing the viability of normal human dermal fibroblast (NHDF) cells treated with gatifloxacin. Almost all NHDF cells survived after 2-d culture, while 81% of the cells survived after 4-d culture when treated with 1.0 × 103 nM gatifloxacin. These results indicate that gatifloxacin is a possible drug for local administration to prevent periodontal infection.

Enzyme-instructed hybrid nanogel/nanofiber oligopeptide hydrogel for localized protein delivery

Enzyme-catalysis self-assembled oligopeptide hydrogel holds great interest in drug delivery,which has merits of biocompatibility,biodegradability and mild gelation conditions.However,its application for protein delivery is greatly limited by inevitable degradation of enzyme on the encapsulated proteins leading to loss of protein activity.Moreover,for the intracellularly acted proteins,cell membrane as a primary barrier hinders the transmembrane delivery of proteins.The internalized proteins also suffer from acidic and enzymatic degradation in endosomes and lysosomes.We herein develop a proteasemanipulated hybrid nanogel/nanofiber hydrogel for localized delivery of intracellularly acted proteins.The embedded polymeric nanogels(CytoC/aNGs)preserve activity of cytochrome c(CytoC)that is an intracellular activator for cell apoptosis as a model protein against proteolysis,and do not affect the gelation properties of the protease-catalysis assembled hydrogels.The injectable hydrogel(CytoC/aNGs/Gel)serves as a reservoir to enhance intratumoral retention and realize sustainable release of CytoC/aNGs.The released CytoC/aNGs increase cellular uptake of CytoC and enhance its intracellular delivery to its target site,cytoplasm,resulting in favorable apoptosis-inducing and cytotoxic effects.We show that a single local administration of CytoC/aNGs/Gel efficiently inhibit the tumor growth in the breast tumor mouse model.