Multiple Responsive Hydrogel Films Based on Dynamic Phenylboronate Bond Linkages with Simple but Practical Linear Response Mode and Excellent Glucose/Fructose Response Speed.

Multiple responsive hydrogels are usually constructed by the addition of many different functional groups. Generally, these groups have different responsive behaviors which lead to interleaved and complex modes of the multi-response system. It is difficult to get a practical application. In this study, we show that multi-response hydrogels can also be constructed using dynamic bonds as crosslinks. The multiple responsive hydrogel films with thicknesses on the sub-micrometer or micrometer scale can be fabricated from P(DMAA-3-AAPBA), a copolymer of N,N-dimethylacrylamide, 3-(acrylamido)phenylboronic acid, and poly(vinylalcohol) (PVA) though a simple layer-by-layer (LbL) technique. The driving force for the film build up is the in situ-formed phenylboronate ester bonds between the two polymers. The films exhibit Fabry-Perot fringes on their reflection spectra which can be used to calculate the equilibrium swelling degree (SDe) of the film so as to characterize its responsive behaviors. The results show that the films are responsive to temperature, glucose, and fructose with simple and practical linear response modes. More importantly, the speed of which the films respond to glucose or fructose is quite fast, with characteristic response times of 45 s and 7 s, respectively. These quick response films may have potential for real-time, continuous glucose or fructose monitoring. With the ability to bind with these biologically important molecules, one can expect that hydrogels may find more applications in biomedical areas in the future.

Precise and tunable time-controlled drug release system using layer-by-layer films as erodible coatings.

Unlike conventional drug carriers, time-controlled release systems do not release drug immediately, but start to release drug after a predetermined lag time. Coating a drug-loaded core with an erodible barrier is a valid way to defer drug release, however, the complicated erosion behavior of the erodible coatings makes it difficult to predict and tune the lag time. Herein we proposed that dynamic layer-by-layer films, using hydrogen-bonded poly(ethylene glycol)/tannic acid (PEG/TA) film as an example, are ideal erodible coatings, because their erosion mechanism is clear and simple, and they disintegrate at constant rate. As a proof, we demonstrated that the release of bovine serum albumin (BSA) from BMS spheres can be deferred by PEG/TA coating. More importantly, the lag time can be simply tuned by the thickness of the coating. By mixing bimodal mesoporous silica (BMS) spheres coated with different thickness PEG/TA films, multiple pulse release was achieved. Similar release patterns were also successfully achieved in vivo.

Electrostatic wrapping of doxorubicin with curdlan to construct an efficient pH-responsive drug delivery system.

The development of environmentally responsive drug delivery systems for the treatment of cancer has attracted particular interest in recent years. However, the enhancement of drug loading capacity and realization of pH-responsive drug delivery remain challenging. Herein, we employ carboxymethyl curdlan as a hydrophilic carrier to wrap doxorubicin (DOX) directly via electrostatic interaction. The sizes of the formed nanoparticles can be simply tuned by changing their feeding ratios. In particular, the nanoparticles are highly stable in aqueous solution without size variation. In vitro drug release and cytotoxicity assays illustrate that this delivery system can release DOX differentially under various environmental conditions and transport it into cell nuclei efficiently, with comparable therapeutic effect to the free drug. These results suggest that the carrying of antitumor drugs by polysaccharide via electrostatic interaction is a simple but effective way to construct a pH-dependent drug delivery platform.