Miroo Kim

Droplet-born air blowing: Novel dissolving microneedle fabrication

The microneedle-mediated drug delivery system has been developed to provide painless self-administration of drugs in a patient-friendly manner. Current dissolving microneedle fabrication methods, however, require harsh conditions for biological drugs and also have problems standardizing the drug dose. Here, we suggested the droplet-born air blowing (DAB) method, which provides gentle (4-25 °C) and fast (≤10min) microneedle fabrication conditions without drug loss. The amount of drug in the microneedle can be controlled by the pressure and time of droplet dispenser and the air blowing shapes this droplet to the microneedle, providing a force sufficient to penetrate skin. Also, the introduction of a base structure of two layered DAB-microneedle could provide complete drug delivery without wasting of drug. The DAB-based insulin loaded microneedle shows similar bioavailability (96.6±2.4%) and down regulation of glucose level compared with subcutaneous injection. We anticipate that DAB described herein will be suitable to design dissolving microneedles for use in biological drug delivery to patients.

Nanostructured lipid carrier-loaded hyaluronic acid microneedles for controlled dermal delivery of a lipophilic molecule

Nanostructured lipid carriers (NLCs) were employed to formulate a lipophilic drug into hydrophilic polymeric microneedles (MNs). Hyaluronic acid (HA) was selected as a hydrophilic and bioerodible polymer to fabricate MNs, and nile red (NR) was used as a model lipophilic molecule. NR-loaded NLCs were consolidated into the HA-based MNs to prepare NLC-loaded MNs (NLC-MNs). A dispersion of NLCs was prepared by high-pressure homogenization after dissolving NR in Labrafil and mixing with melted Compritol, resulting in 268 nm NLCs with a polydispersity index of 0.273. The NLC dispersion showed a controlled release of NR over 24 hours, following Hixson–Crowell’s cube root law. After mixing the NLC dispersion with the HA solution, the drawing lithography method was used to fabricate NLC-MNs. The length, base diameter, and tip diameter of the NLC-MNs were approximately 350, 380, and 30 μm, respectively. Fluorescence microscopic imaging of the NLC-MNs helped confirm that the NR-loaded NLCs were distributed evenly throughout the MNs. In a skin permeation study performed using a Franz diffusion cell with minipig dorsal skin, approximately 70% of NR was localized in the skin after 24-hour application of NLC-MNs. Confocal laser scanning microscopy (z-series) of the skin at different depths showed strong fluorescence intensity in the epidermal layer, which appeared to spread out radially with the passage of time. This study indicated that incorporation of drug-loaded NLCs into MNs could represent a promising strategy for controlled dermal delivery of lipophilic drugs.

Effect of preoperative prednisolone on clinical postoperative symptoms after surgical extractions of mandibular third molars.

BACKGROUND This study compared postoperative symptoms in patients treated preoperatively with a single dose of ≤20 mg oral steroid during third molar surgery. METHODS A total of 450 patients were categorized randomly into three groups containing 150 patients each. Patients were in their second or third decade and had no specific medical history and findings involving infections of the mandibular third molar area. Two groups received preoperative steroids orally one hour before the operation; one group received 10 mg prednisolone and the other received 20 mg. No steroids were administered to the control group. Patients were asked to report by questionnaire any changes in postoperative symptoms, such as pain, facial oedema, or gastrointestinal disorders, and in masticatory disorders, trismus, or swallowing discomfort. They reported daily from days 1 to 6 post-extraction by evaluating their experience over the preceding 24 hours. RESULTS A single preoperative oral administration of ≤20 mg prednisolone had no significant effect on postoperative symptoms of pain, facial oedema, or gastrointestinal upset, or on masticatory symptoms, trismus, or swallowing discomfort in mandibular third molar surgery. CONCLUSIONS A single oral dose of ≤20 mg prednisolone before third molar extraction may not be helpful for the relief of postoperative symptoms.

Rapid implantation of dissolving microneedles on an electrospun pillar array.

Dissolving microneedles (DMNs), designed to release drugs and dissolve after skin insertion, have been spotlighted as a novel transdermal delivery system due to their advantages such as minimal pain and tissue damage, ability to self-administer, and no associated hazardous residues. The drug delivery efficacy of DMNs, however, is limited by incomplete insertion and the extended period required for DMN dissolution. Here, we introduce a novel DMN delivery system, DMN on an electrospun pillar array (DEPA), which can rapidly implant DMNs into skin. DMNs were fabricated on a pillar array covered by a fibrous sheet produced by electrospinning PLGA solution (14%, w/v). DMNs were implanted into the skin by manual application (press and vibration for 10 s) by tearing of the fibers hung on the 300-μm pillars. Separation of DMNs from the fibrous sheet was dependent on both pillar height and the properties of the fibrous sheet. After evaluation of the implantation and dissolution of DMNs with diffusion of red dye by taking cross-sectional images of porcine skin, the hypoglycemic effect of insulin loaded DEPA was examined using a healthy mouse model. This DMN array overcomes critical issues associated with the low penetration efficiency of flat patch-based DMNs, and will allow realization of patient convenience with the desired drug efficacy.

4‐n‐butylresorcinol dissolving microneedle patch for skin depigmentation: a randomized, double‐blind, placebo‐controlled trial

For effective skin depigmentation, the skin depigmentation agent must be delivered to melanocytes, where melanin is synthesized. Although dissolving microneedle (DMN) is one of the best transdermal drug delivery systems to deliver the active compound, no clinical trial has been conducted in terms of safety and efficacy.

The Troy Microneedle: A Rapidly Separating, Dissolving Microneedle Formed by Cyclic Contact and Drying on the Pillar (CCDP).

In dissolving microneedle (DMN)-mediated therapy, complete and rapid delivery of DMNs is critical for the desired efficacy. Traditional patch-based DMN delivery, however, may fail due to incomplete delivery from insufficient skin insertion or rapid separation of microneedles due to their strong bond to the backing film. Here, we introduce the Troy microneedle, which was created by cyclic contact and drying on the pillar (CCDP), and which enabled simultaneous complete and rapid delivery of DMN. This CCDP process could be flexibly repeated to achieve a specific desired drug dose in a DMN. We evaluated DMN separation using agarose gel, and the Troy microneedle achieved more complete and rapid separation than other, more deeply dipped DMN, primarily because of the Troy’s minimal junction between the DMN and pillar. When Troy microneedles were applied to pig cadaver skin, it took only 15 s for over 90% of encapsulated rhodamine B to be delivered, compared to 2 h with application of a traditional DMN patch. In vivo skin penetration studies demonstrated rapid DMN-separation of Troy microneedles still in solid form before dissolution. The Troy microneedle overcomes critical issues associated with the low penetration efficiency of flat patch-based DMN and provides an innovative route for DMN-mediated therapy, combining patient convenience with the desire drug efficacy.

Effects of Fabrication Errors on the Sensitivity of Nano-Replicated Guided Mode Resonance Protein Sensors

Although an injection molding is a promising method for inexpensive mass production of nanograting substrate for disposable guided mode resonance (GMR) protein sensor, the incomplete filling of nanocavities due to the thick solidified layer in conventional injection molding process may lower the sensitivity of label-free GMR protein sensor. In this study, an instant heating method at the filling stage during the injection molding process was investigated to improve the pattern transcribability of molded nanograting and the sensitivity of fabricated GMR protein sensor. Two types of injection molded nanograting with and without instant heating method were prepared and the effects of pattern fidelity on the performance of fabricated GMR protein sensor were analyzed by theoretical and experimental methods.

Development of a quantitative method for active epidermal growth factor extracted from dissolving microneedle by solid phase extraction and liquid chromatography electrospray ionization mass spectrometry

Dissolving microneedle (DMN), a transdermal drug delivery in which biological drugs are encapsulated in biodegradable and biocompatible polymers, was fabricated using epidermal growth factor (EGF) as a model drug and hyaluronic acid (HA) as a backbone polymeric matrix. After mixing calibration and DMN samples with insulin, an internal standard, solid phase extraction (SPE) was performed to separate EGF and insulin from HA, and then liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) was conducted for microgram-scale quantitation. The method showed good linearity (R2=0.997) within a specified range (1-4μg). Additionally, the decrease in EGF levels during DMN fabrication was compared using the SPE/LC-ESI-MS and enzyme-linked immunosorbent assay (ELISA), a traditional analytical method. The ELISA method detected an EGF loss of only 3.88±4.67%, whereas SPE/LC-ESI-MS detected a loss of 16.75±4.39%. Qualitative analysis by circular dichroism showed wavelength shift and splitting after DMN fabrication indicating that EGF was denatured during DMN fabrication and cell viability test showed SPE/LC-ESI-MS is more accurate and reliable for detecting the amount of active EGF loaded into the DMN than ELISA.

Replication of label-free guided mode resonance filter for protein-sensors using UV nanoimprinting process with metallic nano stamp

Interest in protein sensors using guided-mode resonance (GMR) filters is rapidly growing as the demand for sensitive and reliable protein sensors increases in clinical diagnostic applications and pharmaceutical research. GMR filter-based protein sensors are capable of high sensitivity in the detection of molecular interactions, by measuring the movement of sharp reflectance peaks. We designed a GMR filter by computer simulation, and created a prototype by UV nanoimprinting, using a highly durable metallic nano stamp, which was fabricated by electroforming process with a polymeric master pattern. We also demonstrated the use of this GMR filter as a protein sensor by measuring the peak wavelength value (PWV) and the PWV shift.