Keum-Yong Seong

Visible Light-Triggered On-Demand Drug Release from Hybrid Hydrogels and its Application in Transdermal Patches

On-demand release from stimuli-responsive hydrogels has received great attention due to an increasing clinical need. Here, we have prepared spherical hydrogel beads showing visible light-induced volume change at body temper-ature. By spray injection of the monomer solution using the alginate templ-ating method, hybrid beads of several hundred micrometers, consisting of temperature-responsive poly(N-isopropylacrylamide-co-vinyl-2-pyrrolidinone) hydrogel and magnetite nanoparticles (MNP), are produced. MNP dispersed in the hydrogel matrix absorbed visible light and generated heat, increasing the temperature of the matrix and resulting in shrinkage of the beads proportional to light intensity. It is demonstrated that light-induced volume change of dexamethasone-loaded hybrid beads result in on-demand and localized release of the drug by exposure to moderate visible light. As a potential application of the light-sensitive hybrid hydrogel beads, a transdermal patch is developed that incorporates drug-loaded hydrogel beads in multiple drug reservoirs, achieving enhanced release of a model drug when exposed to visible light. This platform should be applicable to on-demand, sequential, and long-term release of drugs via light exposure.

A self-adherent, bullet-shaped microneedle patch for controlled transdermal delivery of insulin

Abstract Proteins are important biologic therapeutics used for the treatment of various diseases. However, owing to low bioavailability and poor skin permeability, transdermal delivery of protein therapeutics poses a significant challenge. Here, we present a new approach for transdermal protein delivery using bullet‐shaped double‐layered microneedle (MN) arrays with water‐swellable tips. This design enabled the MNs to mechanically interlock with soft tissues by selective distal swelling after skin insertion. Additionally, prolonged release of loaded proteins by passive diffusion through the swollen tips was obtained. The bullet‐shaped MNs provided an optimal geometry for mechanical interlocking, thereby achieving significant adhesion strength (˜ 1.6 N cm− 2) with rat skin. By harnessing the MNs reversible swelling/deswelling property, insulin, a model protein drug, was loaded in the swellable tips using a mild drop/dry procedure. The insulin‐loaded MN patch released 60% of insulin when immersed in saline over the course of 12 h and approximately 70% of the released insulin appeared to have preserved structural integrity. An in vivo pilot study showed a prolonged release of insulin from swellable MN patches, leading to a gradual decrease in blood glucose levels. This self‐adherent transdermal MN platform can be applied to a variety of protein drugs requiring sustained release kinetics. Graphical abstract A bio‐inspired, self‐adherent microneedle (MN) patch is designed for effective transdermal protein drug delivery. The dual‐functional MN patch achieved not only a firm adhesion to live animal skin tissue, but also a prolonged insulin drug delivery following a mild loading process into swellable tips with minimal loss of biofunctionality. This transdermal delivery platform using self‐adherent MN patches can be applied for a variety of protein drugs requiring sustained release kinetics. Figure. No Caption available.

Preparation and Characterization of High Absorptive Cellulose Film Derived from Styela Clava Tunic for Wound Dressing

To establish the optimal conditions for the manufacture of high absortive cellulose film(CF) originated from Styela clava tunic(SCT), the physicochemical properties included absorption was measured in CFs prepared under the various conditions. The highest absorption was observed for SCT-CF20 prepared from the cellulose solution dissolved at 80°C for 20min, although the filtration treatment did not induce any significance alteration. Also, the absorption was higher in SCT-CF20-F prepared by the freeze drying than SCT-CF20-N(ambient air drying) and SCT-CF20-H(heat drying). The addition of porogen(NaHCO3) induced an increase of absorption in SCT-CF20-PF relative to SCT-CF20-F, while the number of interconnected porous structures was enhanced in SCT-CF20-PF. Furthermore, a high level of SK-MEL-2 cells viability was observed in SCT-CF20-PN and SCT-CF20-PF cultured group. These results show that SCT-CF may have high absorption and biocompatibility when prepared from SCT cellulose solution dissolved at 80°C for 20min after addition of porogen and then subjected to freeze drying.

Study for Biodegradability of Cellulose Derived from Styela clava tunics

To investigate the biodegradation of the cellulose powder(CP) derived from Styela clava tunics(SCT), some physico-chemical properties and biodegradability of SCT-CP were measured after the incubation for 45 days. The particles size of SCT-CP prepared with washing, bleaching, drying, and grinding processes was 150-400μm although most of particles (70%) was more than 400μm. The cellulose structures of SCT-CP detected using the X-ray diffraction and DSC analysis was very similar with that of wood pulp powder(WP-CP). The glass transition temperature was not detected in both samples. Furthermore, more than 90% of the SCT-CP was degraded, whereas only over 70% of the WP-CP was degraded after the incubation for 45 days. Therefore, these results suggest the possibility that SCT-CP is particularly applicable to prepare medical fiber and film for disease treatment.

Advances in medical adhesives inspired by aquatic organisms’ adhesion

In biomedicine, adhesives for hard and soft tissues are crucial for various clinical purposes. However, compared with that under dry conditions, adhesion performance in the presence of water or moisture is dramatically reduced. In this review, representative types of medical adhesives and the challenging aspects of wet adhesion are introduced. The adhesion mechanisms of marine mussels, sandcastle worms, and endoparasitic worms are described, and stemming from the insights gained, designs based on the chemistry of molecules like catechol and on coacervation and mechanical interlocking platforms are introduced in the viewpoint of translating these natural adhesion mechanisms into synthetic approaches.

Intracutaneous delivery of gelatins induces lipolysis and suppresses lipogenesis of adipocytes

Due to growing interest in cosmetics and medical applications, therapeutic medications that reduce the amount of local subcutaneous adipose tissue have potential for obesity treatment. However, conventional methods such as surgical operation are restricted due to risk of complications. Here, we report a simple and effective method for local reduction of subcutaneous adipose tissue (AT) by using microneedle-assisted transdermal delivery of natural polymers. After in vitro screening tests, gelatin was selected as a therapeutic polymer to reduce accumulation of AT. An in vitro study showed that the level of released glycerol as an indicator of lipolysis was elevated in isolated adipocytes after gelatin treatment. In addition, gelatins suppressed expression levels of lipogenesis-associated genes. Following application of gelatin microneedle (GMN) patches to high-fat diet (HD)-induced obese rats, the amount of subcutaneous AT at the site of GMN application was significantly reduced, which was also confirmed by histological analysis and micro-computed tomography scanning. In addition, lipogenesis-associated genes were down-regulated in GMN-treated subcutaneous AT. These findings suggest that GMN patches induce lipolysis and simultaneously inhibit lipogenesis, thereby reducing deposition of subcutaneous AT. This platform using GMNs may provide a new strategy to treat excess subcutaneous AT with minimal complications. STATEMENT OF SIGNIFICANCE: (1) Significance This work reports a new approach for the local reduction of subcutaneous adipose tissue using a dissolving microneedle patch prepared using gelatin to enable suppression of lipogenesis and acceleration of lipolysis in adipocytes. The gelatin microneedle patch exhibited a significant reduction of local subcutaneous fat up to 60% compared to control groups without any change in total weight. (2) Scientific impact This is the first report demonstrating the direct anti-obesity effects of gelatin administrated in a transdermal route and the feasibility of natural polymer therapeutics for regional reduction of subcutaneous fat. We believe that our work will excite interdisciplinary readers of Acta Biomaterialia, those who are interested in the natural polymers, drug delivery, and obesity.

Design of a microneedles array with swellable tips for mechanical interlocking with soft tissues

Tissue adhesive has received great attention due to an increasing clinical need. It has been widely used for wound closure, hemostasis, and fixation of tissues. Moreover, since tissue adhesion is essential for the application of drug delivery patches or medical devices, many research efforts have been devoted to the development of adhesives enabling long-term tissue adhesion in clinical setting. However, it is still challenging to achieve a significant adhesion to soft tissues while minimizing tissue damage. Here we have developed a double-layered microneedle array consisting of a poly(styrene)-block-poly(acrylic acid) swellable tip and non-swellable polystyrene core, achieving mechanical interlocking with tissues. With optimum swellable tip height, the patch-type microneedle adhesive showed enhanced adhesion strength to wet skin compared to a flat patch.