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The aim was to investigate the potential of chitosan microspheres (CMs) with different acetylation using as a chemoembolic agent. Chitosan microspheres (CMs) were prepared via water-in-oil (W/O) emulsification cross-linking method, and acetylated chitosan microspheres (ACMs) were obtained by acetylation of CMs. Next, we characterized the morphology, size, composition and degrees of deacetylation using scanning electron microscopy (TEM), dynamic laser light scattering (DLS), and Fourier transform infrared spectrometer (FTIR). All microspheres had smooth surfaces and good mechanical flexibility, and all could pass through a 5F catheter. The swelling rate (SR) of CMs decreased significantly with the increase of pH (4.0–10.0) but ACMs did not change under the same conditions. Protein absorption assays suggested that albumin was more greatly adsorbed on CMs than on ACMs. Furthermore, CMs caused more blood clots than ACMs. ACMs caused hemolysis less than CMs (<5% of the time). Data indicated that ACMs had more hemocompatibility. Cytotoxicity tests indicated that ACMs initially had less cell attached proliferation but increased with incubation. In contrast, the relative growth rate of mouse embryo fibroblasts (MEFs) on CMs decreased gradually. The results suggested that ACMs could stimulate the growth of MEFs, and CMs were not cytotoxic to MEFs. Thus, ACMs were more biocompatible with greater potential to be used as chemoembolic material. [ABSTRACT FROM AUTHOR]

Abstract: Oleoyl-carboxymethyl-chitosan (OCMCS) was synthesized and were soluble at neutral pH. The critical micelle concentration (CMC) of OCMCS in deionized water was 0.021mg/ml. OCMCS nanoparticles were successfully prepared via self-assembly with mean diameter of 215.34nm, zeta potential of 19.26mV and an almost spherical shape as determined by electron microscopy. The OCMCS nanoparticles showed low erythrocyte membrane-damaging effect. The MTT survival assay indicated no significant cytotoxicity to Caco-2 cells and MEFs cells. The uptake of FITC labeled OCMCS nanoparticles by Caco-2 cells was confirmed via confocal laser scanning microscope (CLSM). In vivo toxicity assays were performed via histopathological evaluation, and no specific anatomical pathological changes or tissue damage was observed in the tissues of carps. The extent of tissue distribution and retention following oral administration of FITC-OCMCS nanoparticles was analyzed for 3 days. After 3 days, the nanoparticles remained detectable in the muscle, heart, kidney, liver, intestine, and spleen. The results showed that 34.32% of the particles were localized in the liver, 18.79% in the kidney, and 17.36% in the heart. The lowest percentage was observed in the muscle. These results implied that OCMCS nanoparticles had great potential to be applied as safe carriers for the oral administration of protein drugs. [Copyright &y& Elsevier]

Abstract: In this study, we investigated the antibacterial mechanism through the interfacial contacting inhibition behaviors of chitosan antimicrobials against Escherichia coli in solid dispersing state. Chitosan microspheres (CMs) were prepared by emulsification cross-linking reaction, and oleoyl-CMs (OCMs) were obtained by introduction of oleoyl groups to the chitosan. The CMs were with smooth surface and spherical shape of diameter of about 124μm. The antibacterial activity was directly proportional to the concentration and the hydrophobic property of CMs. The fluorescence experiments indicated CMs had influenced the structure of membrane, especially the OCMs were speculated to interact with proteins on the cell membrane. SEM photographs showed E. coli adhered to the surface of the CMs and provided evidences for the disruption of the cells, while the bacterium conglomerated on the surface of the OCMs. The CMs changed the permeability of membrane and caused cellular leakage that correlated with the hydrophobic interaction between CMs and cytoplasmic membrane phospholipids of Gram-negative bacteria. Solid dispersing system makes the antibacterial activities of CMs counted as a sequent event-driven to study the antibacterial mechanism of chitosan originally. [Copyright &y& Elsevier]

To develop more effective anticancer mucoadhesive drug delivery system for the treatment of colorectal cancer, chitosan based nanogels (NGs) were prepared by electrostatic interaction between chitosan (CS) and carboxymethyl-chitosan (CMCS). By respectively using tripolyphosphate (TPP) and CaCl 2 as ionic crosslinker, two well-characterized doxorubicin hydrochloride (DOX) loaded NGs with opposite zeta potential (DOX:CS/CMCS/TPP NGs, −32.6 ± 1.1 mV and DOX:CS/CMCS/Ca 2+ NGs, +31.8 ± 0.9 mV) were obtained. Compared with DOX:CS/CMCS/TPP NGs, DOX:CS/CMCS/Ca 2+ NGs were taken up to a greater extent by colorectal cancer cells, resulting in greater reduction in percentage of cell viability. Owing to high binding capability to mucin and inhibited paracellular transport by colon, DOX:CS/CMCS/Ca 2+ NGs exhibited improved mucoadhesion and limited permeability. This is beneficial to prolong the contact time of formulation onto intestinal mucosa and improved local drug concentration. The results provided evidence DOX:CS/CMCS/Ca 2+ NGs to be exciting and promising for the treatment of colorectal cancer. [ABSTRACT FROM AUTHOR]

A series of deoxycholate-chitosan-hydroxybutyl (DAHBCs) with different degrees of substitution (DS) of hydrophobic deoxycholate (DOCA) were successfully synthesized. The lower critical solution temperature (LCST) of various DAHBCs could be adjusted from 35.4 °C to 42.1 °C by controlling the graft density of DOCA. DAHBCs could self-assemble into nanoparticles (NPs) which gradually evolved from irregular aggregates to spherical particles with the decrease of the DS of DOCA groups. The size of DAHBCs NPs ranged from 100 nm to 250 nm and their zeta potential varied between 3.85 and 12.37 mV. Hemolysis tests and protein adsorption assay exhibited DAHBCs NPs had few adverse effects on the blood components even at a concentration as high as 1 mg/mL. DAHBCs NPs showed high curcumin (CUR) encapsulation efficiency up to 80%. CUR-loaded DAHBCs NPs displayed thermal-dependent drug release profiles, and the release rate of CUR (∼75%) was significantly ( p < 0.05) accelerated at a temperature above the LCST compared with that (∼40%) below the LCST. Cytotoxicity analysis identified no toxicity associated with DAHBCs NPs at a concentration up to 0.5 mg/mL. However, when the cells were incubated with the CUR-loaded NPs, their growth was significantly inhibited at 43 °C (>LCST), demonstrating the thermal-responsive release of encapsulated cargoes from the NPs. With the capacity to control the LCST of DAHBCs NPs at specific temperatures, it could be speculated that DAHBCs NPs might serve as a promising thermo-responsive nanoplatform for the delivery of antitumor drugs. [ABSTRACT FROM AUTHOR]

Here we described nano-polyplexes (NPs) made of oleoyl-carboxymethy-chitosan (OCMCS)/hyaluronic acid (HA) as novel potential carriers for oral gene vaccines delivery. Aerolysin gene (aerA) of Aeromonas hydrophila as microbial antigen was efficiently loaded to form OCMCS-HA/aerA (OHA) NPs. OHA NPs performed the optimal parameters, i.e. smallest (154.5 ± 9.4 nm), positive charged (+7.9 ± 0.5 mV) and monodispersed system with the N/P ratio of 5 and OCMCS/HA weight ratio of 4. Upon the introduction of HA, OHA NPs was beneficial for the DNA release in intestinal environments in comparison to OA NPs. The mean fluorescence intensity detected in Caco-2 cells incubated with OHA NPs was about 2.5-fold higher than that of OA NPs; however, it decreased significantly in the presence of excess free HA. The OHA NPs and OA NPs decreased the transepithelial electric resistance (TEER) of Caco-2 monolayers obviously and induced increasing the apparent permeability coefficient ( P app ) of DNA by 5.45–6.09 folds compared with free DNA. Significantly higher (P < 0.05) antigen-specific antibodies were detected in serum after orally immunized with OHA NPs than that immunized with OA NPs and DNA alone in carps. These results enable the OHA NPs might resolve challenges arising from gastrointestinal damage to gene antigens, and offer an approach applicable for oral vaccination. [ABSTRACT FROM AUTHOR]