Nae-Gyu Kang

Use of hollow microneedles for targeted delivery of phenylephrine to treat fecal incontinence.

A hollow microneedle (HM) was prepared to deliver a phenylephrine (PE) solution into the anal sphincter muscle as a method for treating fecal incontinence. The goal of this study was the local targeted delivery of PE into the sphincter muscle through the perianal skin with minimal pain using hollow microneedles, resulting in the increase of resting anal sphincter pressure. PE was administered on the left and the right sides of the anus of a rat through the perianal skin using 1.5mm long HM. An in vivo imaging system study was conducted after injection of Rhodamine B, and a histological study was performed after injection of gentian violet. The resting anal sphincter pressure in response to various drug doses was measured by using an air-charged catheter. Anal pressure change produced by HM administration was compared with change produced by intravenous injection (IV), subcutaneous (SC) injection and intramuscular (IM) injection. The change in mean blood pressure produced by HM administration as a function of PE dose was compared with change produced by PBS injection. A pharmacokinetic study of the new HM administration method was performed. A model drug solution was localized in the muscle layer under the perianal skin at the injection site and then diffused out over time. HM administration of PE induced significant contraction of internal anal sphincter pressure over 12h after injection, and the maximum anal pressure was obtained between 5 and 6h. Compared to IV, SC and IM treatments, HM treatment produced greater anal pressure. There was no increase in blood pressure after HM administration of PE within the range of predetermined concentration. Administration of 800μg/kg of PE using HM produced 0.81±0.38h of tmax. Our study suggests that HM administration enables local delivery of a therapeutic dose of PE to the anal sphincter muscle layer with less pain. This new treatment has great potential as a clinical application because of the ease of the procedure, minimal pain, and dose-dependent response.

Evaluation of protein formulation and its viscosity with DSC, DLS, and microviscometer

The viscosity of highly concentrated protein solutions was evaluated using lysozyme as model protein. Viscosity profiles of lysozyme were examined with the effect of buffer and pH-value at various concentrations. The viscosity of lysozyme dissolved in water increased continuously with the concentration as the slope of shear stress against shear rate increased with the concentration. In addition, the viscosity of lysozyme was higher in histidine buffer than in acetate buffer at selected pH ranges. The effect of various excipient concentrations was also investigated in means of unfolding transition temperature (Tm), viscosity, hydrodynamic size and zeta potential by using differential scanning calorimetry (DSC), microviscometer and dynamic light scattering (DLS). The selected excipients except surfactants increased the viscosity of protein solution with their concentration. Carbohydrates increased the viscosity relatively higher than amino acids and also they increased the conformational stability (Tm) by enhancing the protein molecule more in compact form. Also amino acids increased the viscosity but decreased the conformational stability since they seemed to be only dispersed in the solution avoiding protein–protein interactions, resulting in a decrease of zeta potential. Consequently, the applied methods—DSC, DLS and microviscometer demonstrated the potential to develop a highly concentrated protein formulation to decrease the high viscosity effect with acceptable conformational stability.

Towards clinical use of a laser-induced microjet system aimed at reliable and safe drug delivery

Abstract. An Er:YAG laser with 2940-nm wavelength and 250-μs pulse duration is used to generate a microjet that is ejected at ∼50  m/s in air. The strength of the microjet depends on the bubble dynamics from the beam–water interaction within the driving chamber as well as the discharging of the drug solution underneath the elastic membrane that separates the drug from the driving liquid. The jet characteristics, such as velocity, volume, and level of atomization, are obtained by high-speed camera images taken at 42,000 fps. The enhancements in jet volume (dosage) and repeated jet generation, which are aimed at making the injector suitable for general clinical applications, are achieved. The generation of repeated microjets is achieved with the help of a stepping motor that provides a uniform pressure within the drug reservoir before an ejection occurs through a micro nozzle. Also, two types of human growth hormones are used for monitoring any potential thermal damage to the drug solution due to a repeated laser ablation when driving the microjet. We provide strong evidence to support that the drugs, as they are injected to porcine skins, are free of the damage associated with the present delivery method.

Laser-induced microjet injection into preablated skin for more effective transdermal drug delivery

Abstract. A breakthrough in the efficient transdermal delivery of drug via the laser-driven microjet is reported. A single source of laser beam is split into two: one beam ablates a targeted spot on a skin and another beam drives the injector for fast microjet ejection into a preablated spot. This combined ablation and microjet injection scheme using a beam splitter utilizes 1∶4 laser energy sharing between generation of the microhole via ablation and the microjet which is generated using the Er:YAG laser beam at a 2940-nm wavelength and 150-μs pulse duration. A careful analysis of the injection mechanism is carried out by studying the response of the elastic membrane that separates a driving water unit for bubble expansion from a drug unit for a microjet ejection. The efficiency of the present delivery scheme is evaluated by the abdominal porcine skin test using the fluorescein isothiocyanate staining and the confocal microscopy for quantitative delivery confirmation. The depth of penetration and the injected volume of the drug are also confirmed by polyacrylamide gel tests.

Stability of β-Lapachone upon Exposure to Various Stress Conditions: Resultant Efficacy and Cytotoxicity.

Even though β-lapachone is a promising compound with antitumor, antiinflammatory, antineoplastic, and wound-healing effects, there are still issues concerning its chemical stability and degradation mechanisms. The objective of this study was to obtain degradation profiles of β-lapachone and evaluate its chemical stability under various stress conditions. Moreover, the correlation between stability and efficacy was evaluated. The degradation study of β-lapachone was performed using heat, acid, base, oxidation, and light conditions. Kinetics and degradation profiles were investigated with HPLC and LC-MS. The stability indicated in the LC method was validated according to the International Conference on Harmonization guidelines. Human dermal fibroblast (HDF) cells were cultured with the standard and its degraded samples in the cellular activity and cytotoxicity test. β-Lapachone was relatively unstable upon exposure to light, and its photodegradation was accelerated with high relative humidity. Three degradants were identified, and their degradation followed zero-order kinetics. It was shown to degrade to phthalic acid under oxidative conditions, and the degradation kinetics were dependent on the concentration of hydrogen peroxide. Two degradation products were identified upon exposure to basic conditions, which followed first-order kinetics. β-Lapachone was relatively stable under acidic and thermal conditions. It increased the synthesis of collagen compared with the control. However, as the contents decreased, the synthesis of collagen also decreased in the photodegraded samples. β-Lapachone did not exert cytotoxic effects at the effective concentration in the cytotoxicity test. Therefore, in order to ensure efficacy and safety, the chemical stability of β-lapachone needs to be controlled carefully while considering instability mechanisms.

Optical clearing agent reduces scattering of light by the stratum corneum and modulates the physical properties of coenocytes via hydration

The interaction between light and the skin determine how the skin looks to the human eye. Light can be absorbed, scattered, and reflected by different components of the skin in a variety of different ways. Here, we focus on the scattering properties of the outmost layer, the stratum corneum (SC). However, we currently have limited methods with which to distinguish the scattering of light by SC from the changes due to other components of the skin.