Hyungmin Kim

Antioxidant polymeric nanoparticles as novel therapeutics for airway inflammatory diseases.

Successful pulmonary drug delivery requires polymeric drug delivery systems which have excellent biocompatibility and fast degradation rates, when frequent administration is necessary. Here, we report a new family of fully biodegradable hydroxybenzyl alcohol (HBA)-incorporated polyoxalate (HPOX) as a novel therapeutics of airway inflammatory diseases. HPOX was designed to incorporate antioxidant and anti-inflammatory HBA and peroxalate ester linkages capable of reacting with hydrogen peroxide (H2O2) in its backbone. HPOX nanoparticles exhibited highly potent antioxidant and anti-inflammatory effects by scavenging H2O2, reducing the generation of intracellular oxidative stress and suppressing the expression of pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and interleukin (IL)-1β in stimulated macrophages. The potential of HPOX nanoparticles as an anti-asthmatic agent was evaluated using a murine model of asthma. Intratracheal administration of HPOX nanoparticles remarkably reduced the recruitment of inflammatory cells and expression of pro-inflammatory mediators such as IL-4 and iNOS. Based on their excellent antioxidant, anti-inflammatory and anti-asthmatic activities, we believe that HPOX nanoparticles have great potential as therapeutics and drug carriers for the treatment of airway inflammatory diseases such as asthma.

Acid-Degradable Cationic Poly(ketal amidoamine) for Enhanced RNA Interference In Vitro and In Vivo

Efficient delivery of small interfering RNA (siRNA) is one of major challenges in the successful applications of siRNA in clinic. In the present study, we report a new acid-degradable poly(ketal amidoamine) (PKAA) as a siRNA carrier, which has high delivery efficiency and low cytotoxicity. PKAA was designed to have acid-cleavable ketal linkages in the backbone of cationic biodegradable poly(amidoamine). PKAA efficiently self-assembled with siRNA to form nanocomplexes with a diameter of ~200 nm and slightly positive charges, which are stable under physiological conditions, but rapidly release siRNA at acidic pH. PKAA exhibited sufficient buffering capability and endosomolytic activity due mainly to the presence of secondary amine groups in its backbone and rapid degradation in acidic endosomes, leading to the enhanced release of siRNA to cytoplasm. Cell culture studies demonstrated that PKAA is capable of delivering anti-TNF (tumor necrosis factor)-α siRNA to lipopolysaccharide (LPS)-stimulated macrophages and significantly inhibits the expression of TNF-α. A mouse model of acetaminophen (APAP)-induced acute liver failure was used to evaluate in vivo siRNA delivery efficacy of PKAA. PKAA/anti-TNF-α siRNA nanocomplexes significantly reduced the ALT (alanine transaminase) and the hepatic cellular damages in APAP-intoxicated mice. We anticipate that acid-degradable PKAA has great potential as siRNA carriers based on its excellent biocompatibility, pH sensitivity, potential endosomolytic activity, and high delivery efficiency.

Dependence of image flickering of negative dielectric anisotropy liquid crystal on the flexoelectric coefficient ratio and the interdigitated electrode structure

We experimentally measured the splay (e s) and the bend flexoelectric coefficients (e b) of liquid crystal (LC) mixtures with negative dielectric anisotropy and investigated their effect on the image flicker of the LC mixtures driven with a low frequency electric field. Using the experimentally measured e s and e b, we simulated the transmittance (TR) response with the continuum model. First, we confirmed that the TR simulation results were approximated to the experimental data with only small variation. Second, we varied the simulation parameters of e s , e b, the separation (S), and the width (W) of the interdigitated electrodes and tried to find the optimum condition showing the least image flicker. Given W = 3.0 μm and e b = 5.7 pC m−1, it was found that the image flicker could be minimized when the e s /e b value was about 2.4 and the S/W ratio was about 1.5. Because the e s /e b value of the rod-like LC material is generally less than 1, it is desirable to design an interdigitated electrode structure to minimize the image flicker effect.

Fast falling time of fringe-field-switching negative dielectric anisotropy liquid crystal achieved by inserting vertical walls

We report a simulation result in which we obtained a faster falling time of the fringe-field-switching negative dielectric anisotropy liquid crystal (n-FFS) by segregating the subpixel area with vertical walls. By inserting walls near both edges of the interdigitated electrodes, the transmittance (TR) between the walls was increased by a large twist angle of the liquid crystal. The falling time of the n-FFS with 12 walls was 10.5 ms, about 50% less than the n-FFS without a wall (21.3 ms). The maximum TR (TR(max)) of the proposed n-FFS was 26.1%, which was slightly smaller than the TR(max) of the n-FFS without walls (27.8%) but still larger than the FFS with a positive dielectric anisotropy liquid crystal (p-FFS).

Fully biodegradable and cationic poly(amino oxalate) particles for the treatment of acetaminophen-induced acute liver failure

Acute inflammatory diseases are one of major causes of death in the world and there is great need for developing drug delivery systems that can target drugs to macrophages and enhance their therapeutic efficacy. Poly(amino oxalate) (PAOX) is a new family of fully biodegradable polymer that possesses tertiary amine groups in its backbone and has rapid hydrolytic degradation. In this study, we developed PAOX particles as drug delivery systems for treating acute liver failure (ALF) by taking the advantages of the natural propensity of particulate drug delivery systems to localize to the mononuclear phagocyte system, particularly to liver macrophages. PAOX particles showed a fast drug release kinetics and excellent biocompatibility in vitro and in vivo. A majority of PAOX particles were accumulated in liver, providing a rational strategy for effective treatment of ALF. A mouse model of acetaminophen (APAP)-induced ALF was used to evaluate the potential of PAOX particles using pentoxifylline (PTX) as a model drug. Treatment of PTX-loaded PAOX particles significantly reduced the activity of alanine transaminase (ALT) and inhibited hepatic cell damages in APAP-intoxicated mice. The high therapeutic efficacy of PTX-loaded PAOX particles for ALF treatment may be attributed to the unique properties of PAOX particles, which can target passively liver, stimulate cellular uptake and trigger a colloid osmotic disruption of the phagosome to release encapsulated PTX into the cytosol. Taken together, we believe that PAOX particles are a promising drug delivery candidate for the treatment of acute inflammatory diseases.

Electro-optical properties of a nematic liquid crystal aligned with a mixture of nanofibres and polyimide

We examined the electro-optical properties of a nematic liquid crystal sample whose substrates were coated with a mixture of nanofibres (NFs) and polyimide (PI). The samples coated with a NF–PI mixture showed a faster turn-off time than the sample coated with pure PI. We found that the elastic constant and the order parameter of the NF–PI samples were greater than those of the pure PI sample, thus inducing the reduction in turn-off time. The NF–PI mixture-coated surface showed a more homogeneous striped surface topology along the rubbing direction compared to the pure PI surface. The uniform topological anisotropy of the surface seems to be related to the increase in the elastic constant and the order parameter of the NF–PI mixture sample.

Viewing angle compensation of vertical alignment liquid crystal display using a triphenylene-based discotic reactive mesogen

We synthesised a triphenylene-based discotic reactive mesogen 2,3,6,7,10,11-hexakis(but-3-enyloxy)triphenylene (HABET) and investigated its performance as the compensation film for a vertical alignment-liquid crystal display (VA-LCD). The HABET molecule has a negative birefringence with an extraordinary refractive index (ne) that is smaller than the ordinary refractive index (no). The optic axis of the HABET is parallel to the ne direction and was vertically aligned to function as a negative C-plate. We measured the refractive indices and birefringence of the HABET layer in the visible wavelength range. Using the experimental data, we simulated the viewing angle property of the VA-LCD with the HABET negative C-plate and a positive A-plate. The viewing angle property of the VA-LCD with the HABET compensation film was wider than those without the compensation film and those using triacetylcellulose films.

Effect of the ratio between monoacrylate and diacrylate reactive mesogen on the transmission spectrum of polymer-stabilized cholesteric liquid crystal

We investigated the effect of the relative ratio between the diacrylate (DA) and the monoacrylate (MA) reactive mesogen (RM) molecules on the transmission spectrum of polymer-stabilized cholesteric liquid crystal (PSCLC). The reflection color from the top substrate where the UV was exposed was shifted from red to green with increasing the fraction of DA. It was also found that the PSCLC sample with the fraction of DA over 5 wt% formed 2-dimensional poly-grain textures on the bottom substrate. The periodicity of the grains was about 1-2 μm with the consequence of a light-scattering optical texture of the PSCLC sample. By optimizing the relative fraction between MA and DA, we could obtain a vivid broadband PSCLC sample without a scattering of light.

Broadening the reflection bandwidth of polymer-stabilized cholesteric liquid crystal via a reactive surface coating layer

We report a method of broadening the reflection bandwidth of polymer-stabilized cholesteric liquid crystal (PSCLC). The top substrate was consecutively coated with a polyimide (PI) and a reactive mesogen (RM) layer, while the bottom substrate was coated with only PI. We exposed the top substrate with the RM coating to UV light. The reflection bandwidth of the PSCLC samples where the top substrate was over-coated with RM was significantly broader than the samples where both substrates were coated with PI. In addition to the effect of the UV intensity gradient, the RM-coated top substrate has a chemical affinity to bulk RM, promoting formation of the pitch gradient and broadening the reflection bandwidth in the sample.