Junoh Kim

Effect of the layer-by-layer (LbL) deposition method on the surface morphology and wetting behavior of hydrophobically modified PEO and PAA LbL films.

We demonstrate that the surface morphology and surface-wetting behavior of layer-by-layer (LbL) films can be controlled using different deposition methods. Multilayer films based upon hydrogen-bonding interactions between hydrophobically modified poly(ethylene oxide) (HM-PEO) and poly(acrylic acid) (PAA) have been prepared using the dip- and spin-assisted LbL methods. A three-dimensional surface structure in the dip-assisted multilayer films appeared above a critical number of layer pairs owing to the formation of micelles of HM-PEO in its aqueous dipping solution. In the case of spin-assisted HM-PEO/PAA multilayer films, no such surface morphology development was observed, regardless of the layer pair number, owing to the limited rearrangement and aggregation of HM-PEO micelles during spin deposition. The contrasting surface morphologies of the dip- and spin-assisted LbL films have a remarkable effect on the wetting behavior of water droplets. The water contact angle of the dip-assisted HM-PEO/PAA LbL films reaches a maximum at an intermediate layer pair number, coinciding with the critical number of layer pairs for surface morphology development, and then decreases rapidly as the surface structure is evolved and amplified. In contrast, spin-assisted HM-PEO/PAA LbL films yield a nearly constant water contact angle due to the surface chemical composition and roughness that is uniform independent of layer pair number. We also demonstrate that the multilayer samples prepared using both the dip- and spin-assisted LbL methods were easily peeled away from any type of substrate to yield free-standing films; spin-assisted LbL films appeared transparent, while dip-assisted LbL films were translucent.

Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects.

Pharmacokinetic and pharmacodynamic profiles of lorazepam and valproate were analyzed according to uridine 5′‐diphosphate‐glucuronosyltransferase (UGT)2B7 genotype in 14 healthy subjects with UGT2B15*2/*2 genotype. Systemic clearance of lorazepam (2 mg intravenously) and area under the concentration–time curve (AUC) of valproate (600 mg once daily for 4 days) were analyzed as pharmacokinetic parameters, and area under the effect–time curve (AUEC) of psychomotor coordination tests (Vienna) was used for pharmacodynamic parameter. No significant differences were found in systemic clearances of lorazepam by UGT2B7 genotype. AUCs of valproate showed an increasing tendency as the number of UGT2B7*2 alleles increased, but the difference was insignificant. Psychometric results were significant among the UGT2B7 genotype group (AUEC_tracking 261.5±298.9 in *1/*1, and 3,396.8±947 in *2/*2, P=0.047) when the two drugs were coadministered. Our study suggests that the UGT2B7 genotype probably affects lorazepam–valproate pharmacodynamic interaction, especially in subjects who have homovariant genotypes of UGT2B7 and UGT2B15, although the effects on the pharmacokinetics are less significant.

Inhibition effect of Gynura procumbens extract on UV-B-induced matrix-metalloproteinase expression in human dermal fibroblasts

ETHNOPHARMACOLOGICAL RELEVANCEnGynura procumbens Merr. (Asteraceae) has been used as a traditional remedy for various skin diseases in certain areas of Southeast Asia.nnnAIM OF THE STUDYnIn order to evaluate the protective activity of Gynura procumbens extract on skin photoaging and elucidate its mode of action.nnnMATERIALS AND METHODSnMatrix-metalloproteinase (MMP)-1 and -9 expressions were induced by UV-B irradiation in human primary dermal fibroblasts. MMP-1 expression level was measured by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Zymography was employed for evaluating the enzymatic activity of MMP-9. Anti-inflammatory activity and anti-oxidative capacity of the extract were evaluated by ELISA and dichlorodihydrofluorescein diacetate (DCF-DA) assay.nnnRESULTSnThe ethanolic extract of Gynura procumbens inhibited MMP-1 expression up to 70% compare to negative control group. The enzymatic activity of MMP-9 was inhibited around 73% by the treatment of 20μg/mL of the extract. The extract markedly reduced the production of reactive oxygen species (ROS). Gynura procumbens extract showed an inhibitory effect on releasing pro-inflammatory cytokines (IL-6 and IL-8) in human HaCat keratinocyte.nnnCONCLUSIONnThe ethanolic extract of Gynura procumbens inhibited MMP-1 and MMP-9 expressions induced by UV-B irradiation via inhibition of pro-inflammatory cytokine mediator release and ROS production.

Polymer-associated liposomes as a novel delivery system for cyclodextrin-bound drugs.

It is known that cyclodextrins (CDs) extract lipid components from bilayer of liposomes. This could undermine the potential benefits of liposomes as drug carriers. In this study, we demonstrated that PC-Chol liposomes with various CDs or rhapontin (Rh)-hydroxypropyl betaCD (HPbetaCD) complexes could be stabilized by association with the amphiphilic polyelectrolyte, poly(methacrylic acid-co-stearyl methacrylate). Based on the results of differential scanning calorimetry, photocorrelation spectroscopy and transmission electron microscopy, the polymer-associated liposomes had the same vesicular form as liposome with clear boundaries and retained structural integrity for at least 1 month. In addition, the polymer-associated structure was unaffected by the type of CD, the composition and concentration of lipid components, and the concentration of the Rh-HPbetaCD complex. This contrasted with PC-Chol liposomes, whose structure was dependent on these factors. Using structurally different polymer-associated liposomes and PC-Chol liposomes containing the Rh-HPbetaCD complex, we also showed that the stability of vesicles could influence the skin permeability of CD-drug complexes.

The Design of Polymer‐based Nanocarriers for Effective Transdermal Delivery

This study reports a facile and practical means to non-invasively deliver biologically active ingredients through the skin using polymer-based nanocarriers. For this, polymer nanocapsules were fabricated with different surface charges as well as glass transition temperatures and we observed their ability to deliver the encapsulated active ingredient, coenzyme Q10, through the skin layer. Direct imaging of a probe molecule, Nile Red, and a matrix polymer labeled with fluorescence moiety, Lucifer Yellow, allowed us to demonstrate that the probe molecule readily permeates into the deep skin, while the matrix polymer stays in the stratum corneum layer due to electrostatic interactions. Quantitative characterization of the penetrating amount of coenzyme Q10 using the Frantz cell method proved that, to achieve improved delivery efficiency, the nanocapsule should have a low glass transition temperature as well as positive surface charges.

Non‐invasive Transdermal Delivery Route Using Electrostatically Interactive Biocompatible Nanocapsules

This study was supported by a grant of the Korea nHealth 21 R&D Project, Ministry of Health & Welfare, Republic of Korea n(03-PJ1-PG1-CH14-0001).

Template-free uniform-sized hollow hydrogel capsules with controlled shell permeation and optical responsiveness.

This study has established a robust and straightforward method for the fabrication of uniform poly(vinylamine) hydrogel capsules without using templates that combines the dispersion polymerization and the sequential hydrolysis/cross-linking. The particle sizes are determined by the degree of cross-linking as well as by the cross-linking reaction time, while the shell thickness is independent of these variables. Diffusion-limited reactions occur at the periphery of the particles, leading to the formation of hydrogel shells with a constant thickness. The treatment of the surfaces of hollow hydrogel capsules with oppositely charged biopolymers limits the permeability through the shell of species even with low molecular weights less than 400 g/mol. Furthermore, we demonstrated that the hydrogel shell phase decorated with Au nanoparticles can be optically ruptured by exposure to laser pulse, a feature that has potential uses in optically responsive drug delivery.

Quantitative characterization of degradation behaviors of antioxidants stabilized in lipid particles

This study describes a flexible approach that allows us to characterize the long-term stability of antioxidants by using a thermodynamically extended Arrhenius equation. We use retinol, Vitamin A, as a model antioxidant and its degradation behaviors are characterized for both stabilized and non-stabilized systems; in this study, by using a fluid bed technique, we immobilize the retinol in lipid particles, thus increasing its thermal stability in complex formulations, such as aqueous polymer gels and emulsions. Our approach demonstrates that the degradation behaviors of the retinol show a functional relationship with temperature and time, which makes it possible to use the Arrhenius approach. This result allows us to precisely characterize the stability of antioxidants in complex formulations for long time.

Fabrication of microgel-in-liposome particles with improved water retention.

Corneocytes represents the main water reservoir of stratum corneum, and that ability intimately arises from their architecture and total composition. Here we describe a novel method for fabricating a microgel-in-liposome (M-i-L) structure consisting of a sodium hyaluronate microgel and a lipid membrane envelop in order to mimic corneocyte cell structures. The essence of our approach is to use a lecithin-based microemulsion with a very low interfacial tension between the water droplet and oil continuous phase. Using this emulsion enables us to stabilize a dispersion of microgel particles without phase separation or aggregation. The addition of excess water produced single-core or multicore microgel particles enveloped in a lipid layer. To demonstrate the applicability of this unique vesicle system, we encapsulated a high concentration of natural moisturizing factor (NMF) in the microgel core and investigated how the M-i-L structure affected the water retention in comparison with other control systems. We have observed that our M-i-L particles with the NMF in the core, which mimicked the corneocyte cell structure, showed an excellent ability to retain water in the system. This experimental result inspired us to investigate how corneocyte cells, which feature a lipid-enveloped hydrogel structure, provide such long-lasting hydration to the skin.

The mutant a allele function in exon 21 G2677T/A of human MDR1 gene

There are still contradictory reports on the relationship between the MDR1 genotype and disposition of the PGP substrates. The allele frequency for the mutant A allele of the exon 21 G2677T/A (Ala 893Ser/Thr) is about 20% in Asian groups but the frequencies are negligible in the Caucasian and African populations. We hypothesized that as yet unknown A allele function was the one of reasons of contradictory results. This study was performed to clarify the effects of the major MDR1 gene polymorphisms including a mutant A allele in exon 21 on the fexofenadine pharmacokinetics. A single oral dose of 180 mg fexofenadine HCl was administered in 33 healthy Korean male volunteers, who were divided into 6 groups on the basis of the MDR1 haplotype for G2677T/A and C3435T polymorphism. A significant relationship was observed between genotypes and AUCs (p<0.05). 2677AA/3435CC subject group (n=3) showed significant lower AUC(0–24) values than those of other 5 groups (2677/3435: GG/CC, GT/CT, TT/TT, GA/CC, TA/CT). Homozygous 3435TT subjects had significant higher AUC(0–24) and Cmax values than CC subjects who were stratified for genotypes at position 3435 [AUC(0–24) 5934 +/‐ 2064 ng*hr/mL vs 3998 +/‐ 1241 ng*hr/mL, Cmax 958 +/‐ 408 ng/mL vs 673 +/‐ 242 ng/mL; mean +/‐ SD]. It was thought that the A allele variant in exon 21 had more powerful efflux function of PGP than wild type or T allele variant.