Guoguang Niu

Hyperbranched poly(amine-ester) based hydrogels for controlled multi-drug release in combination chemotherapy

Combination chemotherapy has been a primary management for cancer. Thus a drug delivery system which can administer several drugs simultaneously and control the drug release at the cancer site is desired. Here we synthesized hyperbranched poly(amine-ester) (HPAE) macromers with different degrees of terminal CC modification to make injectable hydrogels as a multi-drug delivery system. The aqueous solutions of the macromers were fast transformed into hydrogel at body temperature with a low concentration (0.05 wt%) of ammonium persulfate (APS) but no activator for accelerating the polymerization, since the HPAE macromer with tertiary amines and APS themselves formed a redox system as initiator. Three different types of drugs, doxorubicin hydrochloride (Dox), 5-fluorouracil (5FU) and leucovorin calcium (LC), were used as model drugs in this experiment. This system allows locally releasing single and/or combinations of anticancer drugs simultaneously by a controllable way. Behaviors of drug release can be controlled by the drug-loading methods or/and the CC modification degree of macromers loaded with the drug molecules. The drug release period could be prolonged when the drug was loaded into the macromers with high content of CC. The HPAE macromers exhibited good biocompatibility which was evaluated in L929 and MCF7 cell lines using MTT cell proliferation assay. The swelling behavior and degradation of HPAE hydrogels in vitro were also examined. These results suggest that the HPAE hydrogels hold great potential for use as injectable systems for locally delivering single and/or multiple drugs in chemotherapy of cancer.

Synthesis and characterization of reactive poloxamer 407s for biomedical applications

The drawbacks of poloxamer hydrogel, such as dissolving quickly in aqueous solution, have limited its biomedical application. In order to improve the stability of hydrogel, a novel system was developed by combining the reversible thermo-sensitive property of poloxamer 407 and the thiol-ene reactivity between the acrylate and thiol groups. It was found that the sol-gel transition of the acrylate/thiol modified poloxamer 407 mixture could be achieved at body temperature even with a low concentration of 17.5 wt.%. Meanwhile, the reaction between the acrylate and thiol modified poloxamer 407s occurred spontaneously in mimic physiological conditions, thus the hydrogel with crosslinking structure was formed. As a result, the stability of the crosslinked hydrogel was enhanced remarkably, and the release time of the drug from the crosslinked hydrogel was about 4.0 times as long as that from the poloxamer 407 hydrogel. Invitro and invivo experiments revealed that the biocompatibilities of the modified poloxamer 407 hydrogel were similar to that of poloxamer 407. These results indicate that the modified poloxamer 407s have potential applications in controlled drug release, tissue engineering and cell encapsulation etc.

Thiol/Acrylate-Modified PEO-PPO-PEO Triblocks Used as Reactive and Thermosensitive Copolymers

The reactive thermal-sensitive hydrogels, which combined the reversible thermosensitive and mild reactive property, were designed based on thiol-ene reaction in physiological conditions between thiol and acrylate capped thermosensitive Poloxamer 188. The modified P188A, P188SH, and their reactivity were characterized by (1)H NMR, FT-IR, GPC, DSC, Ellman method, and Rheometer. It was found that the thiol-ene reaction was pH and thermal-sensitive. There was 77.7% SH involved into the reaction at 37.0 degrees C and pH 7.4 within the first 30 min. The most of molecules reacted as CC/SH mol ratio was 1.5. The exothermic thiol-ene reaction was mild, with about DeltaH = -91.18 J/g changes. The multiblocks or network structure limited the dissolution of hydrogel, correspondingly the gels duration and the release time of methylene blue were prolonged to 124 h. The experimental results indicated the reactive thermal-sensitive hydrogels potential applications in drug delivery, tissue engineering, and cell encapsulation.

Tailored (Meth)Acrylate Shape‐Memory Polymer Networks for Ophthalmic Applications

The unique features of shape-memory polymers enables their use in minimally invasive surgical procedures with a compact starting material switching over to a voluminous structure in vivo. In this work, a series of transparent, thermoset (meth)acrylate shape-memory polymer networks with tailored thermomechanics have been synthesized and evaluated. Fundamental trends were established for the effect of the crosslinker content and crosslinker molecular weight on glass transition temperature, rubbery modulus and shape-recovery behavior, and the results are intended to help with future shape-memory device design. The prepared (meth)acrylate networks with high transparency and favorable biocompatibility are presented as a promising shape-memory ophthalmic biomaterial.

Synthesis and characterization of acrylamide/N-vinylpyrrolidone copolymer with pendent thiol groups for ophthalmic applications.

Injectable acrylamide/N-vinylpyrrolidinone copolymers with pendent thiol groups were prepared by a radical polymerization and reductive dissolution reaction. The solution of copolymers was re-gelled through oxidation in air or the thiol-disulfide exchange reaction. The re-gelation time could be adjusted from several minutes to several hours by changing the amount of the disulfide exchange reagent. The re-gelled hydrogels possessed high transmittance in the visible region but could block out some of the ultraviolet radiation. Their refractive indexes ranged from 1.34 to 1.35, and their equilibrium water contents were over 95.0%. The morphologies of the hydrogels were analyzed and the porous structure, with pore sizes of 50-300 microm, was noted. The cytotoxicities of the hydrogels were clearly reduced compared with previous results. The experimental results indicated that the injectable copolymers could be used as an artificial vitreous substance or as a scaffold for lens regeneration.

Synthesis and Characterization of Shape Memory (Meth)Acrylate Co-Polymers and their Cytocompatibility In Vitro.

A series of novel transparent shape memory co-polymers, made from (meth)acrylate monomers, intended to be used as intraocular lens, was synthesized. The thermo-mechanical properties, shape memory properties and optical properties of the co-polymers could be adjusted by using monomers with various alkyl chain lengths. The cytocompatibility of the prepared co-polymers to L929 mouse connective tissue fibroblasts was demonstrated in vitro, and the co-polymers exhibited favorable cytocompatibility, supporting cell viability and proliferation. This study showed that the prepared co-polymers, which exhibited good flexibility, adjustable shape memory properties, high transparency and favorable cytocompatibility, could find great promising applications as intraocular lens.

Studies on the electro‐optical properties of polymer stabilised cholesteric liquid crystal/aerosil particles composites

Normal‐mode polymer stabilised cholesteric liquid crystal (Ch‐LC)/aerosil particles (APs) composites are prepared by photo‐polymerisation of the photo‐polymerisable monomer in the electrically induced homeotropically oriented cholesteric phase of a photo‐polymerisable monomer/Ch‐LC/APs mixture. On the application of an electric field, the composites can change from a light scattering state to a transparent state accompanied by the texture changing from a focal conic texture to an electrically induced homeotropic texture. Moreover, the process was greatly influenced by the addition of the APs. The focus of this study is on the effects of the APs on the electro‐optical performance and the morphology of polymer network of the composites. The effect of the chiral dopant concentration on the electro‐optical performance is also studied.