An alginate/poly(N-isopropylacrylamide)-based composite hydrogel dressing with stepwise delivery of drug and growth factor for wound repair.

Anti-inflammation and angiogenesis play an essential role in wound healing. In this study, we developed a composite hydrogel dressing with stepwise delivery of diclofenac sodium (DS) and basic fibroblast growth factor (bFGF) in the inflammation stage and new tissue formation stage respectively for wound repair. Sodium alginate (SA) crosslinked by calcium ion acted as the continuous phase, and thermosensitive bFGF-loaded poly(N-isopropylacrylamide) nanogels (pNIPAM NGs, LCST1 ~33 °C) and DS-loaded p(N-isopropylacrylamide-co-acrylic acid) nanogels [p(NIPAM-co-AA) NGs, LCST2 ~40 °C] acted as the dispersed phase. The synthesized SA/bFGF@pNIPAM/DS@p(NIPAM-co-AA) hydrogel presented a desirable storage modulus of ~4500 Pa, a high water equilibrium swelling ratio of ~90, an appropriate water vapor transmission rate of ~2300 g/m2/day, and nontoxicity to human skin fibroblasts. The in vitro thermosensitive cargo delivery of this hydrogel showed that 92% of DS was sustainably delivered at 37 °C within the early three days mimicking the inflammation stage, while 80% of bFGF was controlled released at 25 °C within the later eight days mimicking new tissue formation stage. The in vivo wound healing of rats showed that this composite hydrogel presented a better healing effect with a wound contraction of 96% at 14 d, less inflammation and higher angiogenesis, than all control groups. These findings indicate SA/bFGF@pNIPAM/DS@p(NIPAM-co-AA) composite hydrogel is a potential dressing for wound repair.

Poly(2-hydroxyethyl methacrylate)/ß-cyclodextrin-hyaluronan contact lens with tear protein adsorption resistance and sustained drug delivery for ophthalmic diseases.

A series of poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels containing cross-linked ß-cyclodextrin-hyaluronan (ß-CD-crHA), with tear protein adsorption resistance and sustained drug delivery, were developed as contact lens materials for eye diseases. ß-CD-HA was synthesized from aminated ß-CD and HA and then crosslinked within pHEMA hydrogel using polyethylenimine as a crosslinker. The synthesized ß-CD-HA was characterized by 1H NMR analysis, and ß-CD-crHA immobilized in pHEMA hydrogel was confirmed by FT-IR, SEM, and AFM analyses. The incorporation of ß-CD-crHA significantly improved the surface hydrophilicity, water uptake ability, oxygen permeability, and flexibility of pHEMA hydrogel, but did not compromise light transmission. pHEMA/ß-CD-crHA hydrogels not only decreased the tear protein adsorption because of the electrostatically mutual repulsion and the improved hydrophilicity, leading to the reduced adhesion of Staphylococcus aureus on the hydrogel surface, but also enhanced the encapsulation capacity and the sustainable delivery of diclofenac due to the formation of inclusion complexes between ß-CD and drugs. All the hydrogels were nontoxic to 3T3 mouse fibroblasts by in vitro cell viability analysis. Among these hydrogels with different ß-CD-crHA contents, pHEMA/ß-CD-crHA10 hydrogel showed the lowest water contact angle of 52 °, the highest water content of 65%, the largest Dk value of 36.4 barrer, and the optimal modulus of 1.8 MPa, as well as a good light transmission of over 90%. The in vivo conjunctivitis treatment of rabbits for 72 h indicated that drug-loaded pHEMA/ß-CD-crHA10 hydrogel presented a better therapeutic effect than both one dose administration of drug solution per day and drug-loaded pHEMA hydrogel. Thus, pHEMA/ß-CD-crHA10 hydrogel is a promising contact lens material for ophthalmic diseases. STATEMENT OF SIGNIFICANCE: Topical eye drops are currently the most popular treatment for ophthalmic diseases, but frequent dosing is necessary to acquire the desirable clinical effect at the expense of systemic side-effects. Drug-loaded contact lenses, as an alternative of eye drops, possess many good performances and show potential applications. However, the sustained drug delivery and the tear protein adsorption resistance are still challenging for contact lenses. Hence, we developed a novel pHEMA/ß-CD-crHA hydrogel by incorporating ß-CD-crHA crosslinked network into pHEMA hydrogel. Besides the improvements in surface hydrophilicity, water uptake ability, oxygen permeability, and flexibility, pHEMA/ß-CD-crHA hydrogel also reduced the adsorption of tear proteins and the adhesion of Staphylococcus aureus, enhanced the drug encapsulation, and prolonged the drug delivery, with better effect in the conjunctivitis treatment of rabbits. Thus, pHEMA/ß-CD-crHA hydrogel is a potential contact lens material for treating ophthalmic diseases.

Direct Writing Supercapacitors Using a Carbon Nanotube/Ag Nanoparticle-Based Ink on Cellulose Acetate Membrane Paper.

In this work, we present a cellulose acetate membrane flexible supercapacitor prepared through a direct writing method. A carbon nanotube (CNT) and silver (Ag) nanoparticle were prepared into ink for direct writing. The composite electrode displayed excellent electrochemical and mechanical electrochemical performance. Furthermore, the CNT-Ag displayed the highest areal capacity of 72.8 F/cm3. The assembled device delivered a high areal capacity (17.68 F/cm3) at a current density of 0.5 mA/cm2, a high areal energy (9.08-5.87 mWh/cm3) at a power density of 1.18-0.22 W/cm3, and showed no significant decrease in performance with a bending angle of 180°. The as-fabricated CNT/Ag electrodes exhibited good long-term cycling stability after 1000 time cycles with 75.92% capacitance retention. The direct writing was a simple, cost-effective, fast, and non-contact deposition method. This method has been used in current printed electronic devices and has potential applications in energy storage.

In Situ Growth of a High-Performance All-Solid-State Electrode for Flexible Supercapacitors Based on a PANI/CNT/EVA Composite.

For the development of light, flexible, and wearable electronic devices, it is crucial to develop energy storage components combining high capacity and flexibility. Herein, an all-solid-state supercapacitor is prepared through an in situ growth method. The electrode contains polyaniline deposited on a carbon nanotube and a poly (ethylene-co-vinyl acetate) film. The hybrid electrode exhibits excellent mechanical and electrochemical performance. The optimized few-layer polyaniline wrapping layer provides a conductive network that effectively enhances the cycling stability, as 66.4% of the starting capacitance is maintained after 3000 charge/discharge cycles. Furthermore, the polyaniline (PANI)-50 displays the highest areal energy density of 83.6 mWh·cm-2, with an areal power density of 1000 mW·cm-2, and a high areal capacity of 620 mF cm-2. The assembled device delivers a high areal capacity (192.3 mF·cm-2) at the current density of 0.1 mA·cm-2, a high areal energy (26.7 mWh·cm-2) at the power density of 100 mW·cm-2, and shows no significant decrease in the performance with a bending angle of 180°. This unique flexible supercapacitor thus exhibits great potential for wearable electronics.

Cationic nano-copolymers mediated IKKbeta targeting siRNA inhibit the proliferation of human Tenon's capsule fibroblasts in vitro.

PURPOSE: To synthesize a ternary cationic copolymer called CS-g-(PEI-b-mPEG) and characterize its features as a non-viral siRNA carrier; in turn, to investigate the influence of small interfering RNA (siRNA) targeting IkappaB kinase subunit beta (IKKbeta) on the proliferation of human Tenon's capsule fibroblasts (HTFs) in vitro. METHODS: First, a novel cationic copolymer composed of low molecular weight, linear poly(ethyleneimine) [PEI] blocked with polyethylene glycol (PEG) and grafted onto a chitosan (CS) molecule was synthesized. CS-g-(PEI-b-mPEG) was then compacted with 21nt siRNA at various copolymer/siRNA charge (N/P) ratios, and the resulting complexes were characterized by dynamic light scattering, gel electrophoresis, and serum incubation. Cell Titer 96 AQ(ueous) One Solution cell proliferation assay was used to investigate the cytotoxicity of this cationic copolymer. Second, siRNAs targeting IKKbeta (IKKBeta-siRNAs) were delivered into the HTFs using CS-g-(PEI-b-mPEG) as the vehicle. Real-time reverse transcription polymerase chain reaction (RT-PCR) subsequently assessed the mRNA level of IKKbeta, and western blot assay was used to determine protein expression. After IKKB-siRNA transfection, Cell Titer 96 AQ(ueous) One Solution cell proliferation assay was used to evaluate the proliferation of HTFs. RESULTS: The diameter of the CS-g-(PEI-b-mPEG)/siRNA complexes tended to decrease whereas their zeta potential tended to increase as the N/P ratio increased. The CS-g-(PEI-b-mPEG) copolymer showed good siRNA binding ability and high siRNA protection capacity. Furthermore, the copolymer presented remarkable transfection efficiency and showed much less cytotoxicity than 25 kDa PEI. IKKB-siRNAs were successfully delivered into HTFs using CS-g-(PEI-b-mPEG) as a vector. As a result, the expression of IKKbeta was downregulated at both the mRNA and protein levels, and the activation of nuclear factor-kappaB (NF-kappaB) in the HTFs was subsequently inhibited. Most impressively, the proliferation of HTFs was also effectively suppressed through the blocking of the NF-kappaB pathway. CONCLUSIONS: All the results demonstrate that CS-g-(PEI-b-mPEG) is a promising candidate for siRNA delivery, featuring excellent biocompatibility, biodegradability, and transfection efficiency. The RNA interference (RNAi) strategy using cationic copolymers as siRNA carriers will be a safe and efficient anti-scarring method following glaucoma filtration surgery.

Preparation and characterization of cationic chitosan-modified poly(D,L-lactide-co-glycolide) copolymer nanospheres as DNA carriers.

Chitosan (CS)-modified poly(D,L-lactide-co-glycolide) (PLGA/CS) nanoparticles with cationic surface were prepared by means of emulsion-solvent evaporation technique using polyviny alcohol and chitosan as costabilizers. The preparation conditions of the cationic nanoparticles were optimized by orthogonal factorial design, and the influences of the experiment variables such as polymer concentration, the molecular weight of chitosan, etc., on the size and zeta potential of the nanoparticles were evaluated. It was shown that the diameter of the PLGA/CS nanoparticles can be controlled in the range of 150-200 nm as determined by dynamic light scattering with the optimized conditions. The zeta potential of PLGA/CS nanoparticles increased with increasing the concentration of CS (C(CS)) or decreasing the pH, it was up to 55 mV when C(CS) was 3 mg/mL at pH 4 and inversed around pH 8. The optimization conditions for fabricating the relatively small diameter and high zeta potential cationic nanoparticles were C(CS) 3 mg/mL, C(PLGA) 10 mg/mL, and the volume ratio of organic solution to aqueous medium 1/4. X-ray photo electron spectroscopy and fluorescence inverted microscope observations approved that CS molecules were adsorbed on the surface of PLGA nanoparticles, DNA-condensing ability of the PLGA/CS nanoparticles and cell transfection efficiency of the nanoparticle-DNA complexes were estimated by gel electrophoresis and transfection experiment to 293FT cell, respectively.