Ruixue Yin

Glucose-responsive insulin delivery microhydrogels from methacrylated dextran/concanavalin A: Preparation and in vitro release study

Glucose-responsive systems are very important for self-regulated insulin delivery. The aim of the present study was to evaluate the potential of insulin loaded microhydrogels fabricated from methacrylate derivatives of dextran (Dex-G) and concanavalin A (Con A-E) as a insulin delivery system releasing insulin in response to different glucose levels. Insulin-loaded microhydrogels were prepared through a reversed-phase emulsion crosslinking method. The morphology and size of obtained microhydrogels were characterized by SEM, fluorescence microscope and dynamic light scattering, which showed that these microhydrogels were formed with sphere-like shape and diameters less than 5 μm. In vitro release of insulin from these microhydrogels and release kinetics were studied. The results indicated that insulin release was reversible in response to different glucose concentrations and the released insulin was shown to remain active since the tertiary structure was not destroyed. The degree of substitution (DS) of dextran methacrylate derivatives had effects on the release rate and surface burst release of the microhydrogels and high DS of Dex-G (DS 32) restricted the glucose sensitivity of the microhydrogels. The MTT assay from L929 cell line indicated that these microhydrogels possessed noncytotoxicity. The results suggested that these microhydrogels might be suitable for self-regulated insulin delivery and find potential applications in biomedical fields.

Glucose and pH dual-responsive concanavalin A based microhydrogels for insulin delivery.

Glucose and pH dual-responsive microhydrogels based on concanavalin A (Con A) were prepared and used for insulin delivery. The combination of the specific saccharide-binding affinity of Con A and the cationic groups of N-(2-(dimethylamino) ethyl)-methacrylamide (DMAEMA) led to dual-responsive systems. SEM, fluorescence microscopy and particle size analysis showed that the obtained microhydrogels had a dense surface morphology and an average size of 38 μm. The in vitro insulin release study revealed that the microhydrogels could quickly respond to the changes of glucose concentrations in the medium and small change in pH value of the environment. The kinetics of insulin release was analyzed by using empirical equation and the apparent diffusion coefficient was calculated according to a solution of Ficks second law. The released insulin was proved to remain active. The result suggested that this microhydrogel might find potential applications for self-regulated insulin delivery, actuators and separation systems with sensitivity to glucose.

Freeze-dried chitosan–sodium hyaluronate polyelectrolyte complex fibers as tissue engineering scaffolds

The present work was focused on the preparation and characterization of polyelectrolyte complex (PEC) fibers based on the natural oppositely charged biopolymers, chitosan and sodium hyaluronate, via a freeze-drying method. The physical structure and chemical properties of the freeze-dried fibers were characterized by means of Fourier transform infrared spectroscopy (FT-IR), solid-state 13C nuclear magnetic resonance (13C-NMR) and X-ray diffraction (XRD). The morphology, size, and surface structure of the freeze-dried PEC fibers were observed by means of scanning electron microscopy (SEM). An indirect in vitro cytotoxicity test showed the extracts of fibers had no significant effects on cell viability. Moreover, an in vitro cytocompatibility test exhibited cell population and spreading tendency, suggesting the fibers were non-toxic to L929 cells. All the results indicated that such freeze-dried PEC fibers might have potential applications in tissue engineering scaffolds.

Preparation and properties of cyclic acetal based biodegradable gel by thiol-ene photopolymerization.

Synthetic, hydrolytically degradable biomaterials have been widely developed for biomedical use; however, most of them will form acidic products upon degradation of polymer backbone. In order to address this concern, we proposed to fabricate a biodegradable gel based on the crosslinking of a cyclic acetal monomer with reactable diallyl group and multifunctional thiols by thiol-ene photopolymerization. This gel produces diols and carbonyl end groups upon hydrolytic degradation and could be entirely devoid of acidic by-products. Real time infrared spectroscopy was employed to investigate the effect of different light intensities and concentrations of photoinitiator on the polymerization kinetics. With the increase of the concentration of photoinitiator and light intensity, both the rate of polymerization and final double bond conversion increased. Degradation of cyclic acetal based networks was investigated in PBS medium so as to simulate physiological conditions. The remaining mass of the materials after 25 days incubation was 84%. TGA analysis showed that the gels exhibited a typical weight loss (97.2%) at around 378 °C. In vitro cytotoxicity showed that the cyclic acetal based gels had non-toxicity to cell L-929 and had good biocompatibility.

Glucose-responsive microhydrogels based on methacrylate modified dextran/concanavalin A for insulin delivery.

Summary Glucose-responsive microhydrogels based on methacrylate derivatives of dextran and concanavalin A have been prepared and used for self-regulated insulin delivery. Insulin release from these microhydrogels was in response to different glucose concentrations in the medium and the glucose sensitivity was reversible. The released insulin was proved to remain active without destroying the tertiary structure. The degree of substitution (DS) of the dextran methacrylate derivative had effect on the glucose sensitivity of the microhydrogels.

Synthesis and characterization of water-soluble glucosyloxyethyl acrylate modified chitosan

A novel water-soluble chitosan derivative, glucosyloxyethyl acrylated chitosan was successfully synthesized by Michael addition reaction of chitosan with glucosyloxyethyl acrylate (GEA), and the obtained glyco-chitosan derivative was characterized by FT-IR, (1)H NMR, elemental analysis, XRD, TG, DSC and SEM. The FT-IR and (1)H NMR results showed that GEA residues were grafted onto the amino group of chitosan. The degree of substitution (DS) was calculated by elemental analysis. XRD data revealed that the introduced saccharide moieties decreased the crystalline structure of chitosan. TG and DSC results demonstrated that the glucosyloxyethyl acrylated chitosan was less thermal stable than chitosan. This efficient synthetic method provided an approach of preparing water-soluble glyco-chitosan derivatives. The obtained derivatives would show stronger specific affinity of lectin than chitosan thus would have potential applications in biomaterials.

Synthesis and photopolymerization kinetics of a single-molecular hydrogen-abstract free radical photoinitiator 1,3-Benzodioxole-5-yl-Methyl-Maleimide

1,3-benzodioxole-5-yl-methyl-maleimide (BDOMM), a type of hydrogen-abstraction photoinitiator with both hydrogen donor and acceptor in one molecule for free radical photopolymerization, was synthesized through the reaction of piperonyl amine and maleic anhydride and characterized by IR, UV and 1H NMR spectroscopy. The results obtained indicated that the introduction of BDOMM could avoid the use of additional amine coinitiator, decrease the leachablity of photoinitiator and maintain high photo-initiation efficiency.