Development of drug-loaded chitosan-vanillin nanoparticles and its cytotoxicity against HT-29 cells.

Chitosan as a natural polysaccharide derived from chitin of arthropods like shrimp and crab, attracts much interest due to its inherent properties, especially for application in biomedical materials. Presently, biodegradable and biocompatible chitosan nanoparticles are attractive for drug delivery. However, some physicochemical characteristics of chitosan nanoparticles still need to be further improved in practice. In this work, chitosan nanoparticles were produced by crosslinking chitosan with 3-methoxy-4-hydroxybenzaldehyde (vanillin) through a Schiff reaction. Chitosan nanoparticles were 200-250 nm in diameter with smooth surface and were negatively charged with a zeta potential of - 17.4 mV in neutral solution. Efficient drug loading and drug encapsulation were achieved using 5-fluorouracil as a model of hydrophilic drug. Drug release from the nanoparticles was constant and controllable. The in vitro cytotoxicity against HT-29 cells and cellular uptake of the chitosan nanoparticles were evaluated by methyl thiazolyl tetrazolium method, confocal laser scanning microscope and flow cytometer, respectively. The results indicate that the chitosan nanoparticles crosslinked with vanillin are a promising vehicle for the delivery of anticancer drugs.

Targeted delivery of 5-fluorouracil to HT-29 cells using high efficient folic acid-conjugated nanoparticles.

The incorporation of a high percentage of targeting molecules into drug delivery system is one of the important methods for improving efficacy of targeting therapeutic drugs to cancer cells. PLGA-based drug delivery carriers with folic acid (FA) as targeting molecule have a low targeting efficiency due to a low FA conjugation ratio. In this work, we fabricated a FA-conjugated PLGA system using a crosslinker 1, 3-diaminopropane and have achieved a high conjugation ratio of 46.7% (mol/mol). The as-prepared PLGA-based biomaterial was used to encapsulate therapeutic drug 5-fluorouracil (5-FU) into nanoparticles. In the in vitro experiments, an IC50 of 5.69 µg/mL has been achieved for 5-FU loaded PLGA-1, 3-diaminopropane-folic acid nanoparticles on HT-29 cancer cells and is significantly lower than that of 5-FU and 5-FU loaded PLGA nanoparticles which only have an IC50 of 22.9 and 14.17 µg/mL, respectively. The fluorescent microscopy images showed that nanoparticles with FA are largely taken up by HT-29 cancer cells and the targeting nanoparticles have more affinity to cancer cells than the pure drugs and untreated nanoparticles. Therefore, the 1, 3-diaminopropane can facilitate the conjugation of FA to PLGA to form a novel polymer and 5-FU loaded PLGA-1, 3-diaminopropane-folic acid nanoparticles can be a highly efficient system for specific delivery of drugs to cancer cells.

Retention of the original LLC structure in a cross-linked poly(ethylene glycol) diacrylate hydrogel with reinforcement from a silica network.

Cross-linked poly(ethylene glycol) diacrylate (PEGDA) hydrogels with uniformly controlled nanoporous structures templated from hexagonal lyotropic liquid crystals (LLC) represent separation membrane materials with potentially high permeability and selectivity due to their high pore density and narrow pore size distribution. However, retaining LLC templated nanostructures is a challenge as the polymer gels are not strong enough to sustain the surface tension during the drying process. In the current study, cross-linked PEGDA gels were reinforced with a silica network synthesized via an in situ sol-gel method, which assists in the retention of the hexagonal LLC structure. The silica precursor does not obstruct the formation of hexagonal phases. After surfactant removal and drying, these hexagonal structures in samples with a certain amount of tetraethoxysilane (TEOS) loading are well retained while the nanostructures are collapsed in samples without silica reinforcement, leading to the hypothesis that the reinforcement provided by the silica network stabilizes the LLC structure. The study examines the conditions necessary for a sufficient and well dispersed silica network in PEGDA gels that contributes to the retention of original LLC structures, which potentially enables broad applications of these gels as biomedical and membrane materials.

Synthesis and characterization of folate conjugated chitosan and cellular uptake of its nanoparticles in HT-29 cells.

Folate-chitosan (FA-CS) conjugates synthesized by coupling FA with CS render new and improved functions because the original properties of CS are maintained and the targeting ligand of FA is incorporated. In this work, FA-CS conjugates were synthesized based on chemical linking of carboxylic group of FA with amino group of CS as confirmed by Fourier transform spectroscopy (FTIR) and nuclear magnetic resonance ((1)H NMR). FA-CS conjugates displayed less crystal nature when compared to CS. The FA-CS nanoparticles (NPs) were prepared by crosslinking FA-CS conjugates with sodium tripolyphosphate (STPP). Positively charged FA-CS nanoparticles were spherical in shape with a particle size of about 100 nm. Cellular uptake of CS or FA-CS nanoparticles was assayed by fluorescent microscopy using calcein as fluorescent marker in colon cancer cells (HT-29). The FA-CS nanoparticles exhibited improved uptake of HT-29 and could become a potential targeted drug delivery system for colorectal cancer.

Self-assembled natural rubber/silica nanocomposites: Its preparation and characterization.

A novel natural rubber/silica (NR/SiO2) nanocomposite is developed by combining self-assembly and latex-compounding techniques. The results show that the SiO2 nanoparticles are homogenously distributed throughout NR matrix as nano-clusters with an average size ranged from 60 to 150 nm when the SiO2 loading is less than 6.5 wt%. At low SiO2 contents (⩽4.0 wt%), the NR latex (NRL) and SiO2 particles are assembled as a core-shell structure by employing poly (diallyldimethylammonium chloride) (PDDA) as an inter-medium, and only primary aggregations of SiO2 are observed. When more SiO2 is loaded, secondary aggregations of SiO2 nanoparticles are gradually generated, and the size of SiO2 cluster dramatically increases. The thermal/thermooxidative resistance and mechanical properties of NR/SiO2 nanocomposites are compared to the NR host. The nanocomposites, particularly when the SiO2 nanoparticles are uniformly dispersed, possess significantly enhanced thermal resistance and mechanical properties, which are strongly depended on the morphology of nanocomposites. The NR/SiO2 has great potential to manufacture medical protective products with high performances.

Thermal degradation kinetics and morphology of natural rubber/silica nanocomposites.

A novel natural rubber/silica (NR/SiO2) nanocomposite with a SiO2 loading of 4 wt% is developed by incorporating latex compounding with self-assembly techniques. The SiO2 nanoparticles are homogenously distributed throughout the NR matrix as spherical nano-clusters with an average size of 75 nm. In comparison with the host NR, the thermal resistance of the nanocomposite is significantly improved. The degradation temperatures (T), reaction activation energy (E), and reaction order (n) of the nanocomposite are markedly higher than those of the pure NR, due to significant retardant effect of the SiO2 nanoparticles.

Poly(vinyl alcohol)/silica nanocomposites: morphology and thermal degradation kinetics.

The morphology of self-assembled poly(vinyl alcohol)/silica (PVA/SiO2) nanocomposites is investigated with atomic force microscopy (AFM) and transmission electron microscopy (TEM). It is found that the SiO2 nanoparticles are homogenously distributed throughout the PVA matrix in a form of spherical nano-cluster. The average size of the SiO2 clusters is below 50 nm at the low contents (SiO2 < or =5 5 wt%), while particle aggregations are clearly observed and their average size markedly increases to 110 nm when 10 wt% SiO2 is loaded. The thermogravimetric analysis (TGA) shows that the nanocomposite significantly outperforms the pure PVA in the thermal resistance. By using a multi-heating-rate method, the thermal degradation kinetics of the nanocomposite with a SiO2 content of 5 wt% is compared to the PVA host. The reaction activation energy (E) of the nanocomposite, similar to the pure PVA, is divided into two main stages corresponding to two degradation steps. However, at a given degradation temperature, the nanocomposite presents much lower reaction velocity constants (k), while its E is 20 kJ/mol higher than that of the PVA host.