Xinjie Zhang

Fabrication and evaluation of the novel reduction-sensitive starch nanoparticles for controlled drug release.

A novel type of reduction-sensitive starch nanoparticles was prepared via the reversed-phase microemulsion method by using crosslinker, N,N-bisacryloylcystamine (BAC) with the disulfide linkages, which was specifically cleaved by dithiothreitol (DTT). Starch nanoparticles had a spherical morphology with a small size of 40 nm in the optimal condition. The influences of process parameters (starch amount, surfactant amount and oil/water (O/W) ratio) on the size of starch nanoparticles were studied by dynamic light scattering (DLS). BAC crosslinked starch nanoparticles were degraded into oligomers with the reducing agent of DTT due to the cleavage of the disulfide linkages. A model drug 5-aminosalicylic acid (5-ASA) could be loaded efficiently into starch nanoparticles and the in vitro drug release behaviors were also studied. The results suggested that the disulfide crosslinked starch nanoparticles exhibited an accelerated drug release behavior in the presence of DTT. In vitro methyl thiazolyl tetrazolium (MTT) assays indicated that BAC crosslinked starch nanoparticles had a good biocompatibility when cocultured with human HeLa cancer cells. Hence, with excellent biocompatibility and biodegradability, and rapid drug release in response to DTT, BAC crosslinked starch nanoparticles showed a great potential as a biomaterial carrier for the application of drug controlled release. In contrast to BAC crosslinked starch nanoparticles, N,N-methylenebisacrylamine (MBA) crosslinked starch nanoparticles were prepared as the control without the disulfide linkages.

Physicochemical characterization of amphiphilic nanoparticles based on the novel starch-deoxycholic acid conjugates and self-aggregates.

Novel amphiphilic polymers (starch-deoxycholic acid, St-DCA) were firstly synthesized on the basis of starch (St) as a hydrophilic segment and deoxycholic acid (DCA) as a hydrophobic segment. Hydrophobically modified starch contained 5.4-8.9 deoxycholic acid groups per 100 anhydroglucose units of starch. Self-aggregates of St-DCA conjugates were formed in the PBS media. Physicochemical characterizations of St-DCA conjugates were investigated. The mean sizes of self-aggregates decreased with the degree of substitution (DS) and pH increasing. Zeta potential indicated that nanoparticles were covered with negatively charged starch shells from -5.4 to -23 mV. TEM images demonstrated that nanoparticles were of spherical shape. The critical aggregation concentrations (cac) were dependent on the DS and pH in the range of 0.0185-0.0441 mg/mL. Thus, the study suggested that self-aggregated nanoparticles of St-DCA conjugates could have good pH-responsive and potential application in pharmaceutical and biomedical fields as the delivery of anti-tumor drugs.

Ultra-small and innocuous cationic starch nanospheres: preparation, characterization and drug delivery study.

This research demonstrated the preparation of ultra-small cationic starch nanospheres for the first time. Unlike conventional cationic starch, the cationic starch in here could not form gel. The starch nanoparticles were obtained via reverse micro-emulsion method and were characterized by Fourier transform infrared (FTIR) spectroscopy, Transmission electron microscopy (TEM) and Dynamic light scattering (DLS). The formation mechanism of cationic starch nanospheres was proposed and the effects of preparation conditions on particle size were also investigated. A cationic starch nanosphere with a size of 50 nm can be obtained under the optimal condition. Moreover, the drug release behaviors, cytotoxicity test and degradation analysis were tested and indicated that the particles possess good capacity in delivering the negatively charged molecules, biocompatibility and biodegradability. Thus, the cationic nanoparticles exhibit potential applications in the areas of food and medical sciences.

Ultra-small and anionic starch nanospheres: formation and vitro thrombolytic behavior study.

This paper is considered as the first report on the investigation of nattokinase (NK) release from anionic starch nanospheres. The ultra-small and anionic starch nanospheres were prepared by the method of reverse micro-emulsion crosslinking in this work. Starch nanospheres were characterized through Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and dynamic light scattering (DLS). Effects of preparation conditions on particle size were studied. The cytotoxicity, biodegradable and vitro thrombolytic behaviors of nattokinase (NK) loaded anionic starch nanospheres were also studied. The results showed that the anionic starch nanospheres are non-toxic, biocompatible and biodegradable. Moreover, the anionic starch nanospheres can protect NK from fast biodegradation hence prolongs the circulation in vivo and can reduce the risk of acute hemorrhage complication by decreasing the thrombolysis rate.

Anti-photobleaching flower-like microgels as optical nanobiosensors with high selectivity at physiological conditions for continuous glucose monitoring

Optical glucose detection holds considerable promise for continuous in vivo glucose monitoring with wireless transdermal transmission and long-lasting activity. To construct a new class of optical glucose nanobiosensors with high sensitivity and selectivity at physiological conditions, the first generation of fluorescent poly(amido amine) (G1.0 PAMAM), serving as the optical code, was introduced into glucose-sensitive poly(N-isopropylacrylamide-(2-dimethylamino)ethyl methacrylate-3-acrylamidephenylboronic acid) copolymer microgels via a facile method. The fabricated microgels display the ability of adapting to the surrounding medium of different glucose concentrations over a clinically relevant range (0-20 mM) and convert biochemical signals into optical signals. As nanobiosensors, the G1.0 PAMAM functionalized microgels exhibit high selectivity for glucose over various kinds of potential primary interferents, such as lactate, human serum albumin and metal ions, in the physiologically important glucose concentration range. Compared to traditional fluorescent dyes and quantum dots, which are limited by photobleaching and toxicity, this microgel with remarkable anti-photobleaching property and low toxicity makes it possible to be used for long-term continuous glucose monitoring. Through in vivo investigations, it can be observed that G1.0 PAMAM functionalized microgels can achieve wireless transdermal detection, indicating that the fabricated microgels have potential applications as a new generation of nanobiosensors for the highly sensitive and minimally invasive continuous glucose monitoring.

Fluorescent and thermoresponsive supramolecular systems: synthesis, self-assembly and application in percutaneous optical monitoring

Supramolecular systems were constructed by the non-covalent coupling between PAMAM dendrimers with adamantyl groups and β-cyclodextrin graft PNIPAAm through host-guest interactions. Such supramolecular systems can further self-assemble into nanorods, which have thermoresponsive and excellent fluorescence properties. The injectable and percutaneous detection of fluorescent supramolecular systems will be of significant advantage in the future of biomedical monitoring.

Synthesis and self-assembly of PAMAM/PAA Janus dendrimers

Janus dendrimers have two differently functionalized segments which are located on opposite sides. They have many excellent properties and broad application prospects. In this study, poly(amido amine)/poly(acrylic acid) (PAMAM/PAA) Janus dendrimers were prepared by click chemistry. One of the first steps taken was the synthesis of N-Boc-G3.0 PAMAM dendrimers with primary amine groups at the periphery. Second, by amide coupling between propargylic acid and N-Boc-G3.0 PAMAM, PAMAM dendrimers with alkyne were successfully synthesized. After being dissolved in aqueous solutions with different pH, Janus dendrimers spontaneously form flowerlike micellar, Janus particles, and spherical micelles due to primary amino, tertiary amino, and carboxyl groups in the dendrimers. This self-assembly behavior depending on pH changes has a number of potential applications in the field of materials.