Ih-Seop Chang

New micelle-like polymer aggregates made from PEI-PLGA diblock copolymers: micellar characteristics and cellular uptake

New amphiphilic block copolymers based on oligomeric polyethylenimine and poly(D,L-lactide-co-glycolide) (PEI-PLGA) were synthesized by directly coupling PLGA with a carboxyl terminal group to PEI. The block copolymers were prepared by varying the length of the hydrophobic PLGA block (M(n)=6, 10, and 21K), while that of the hydrophilic PEI block (M(n)=423) was fixed. PEI-PLGA block copolymers were found to be self-assembled in water by using a PLGA segment as a hydrophobic aggregate block and a PEI segment as a hydrophilic corona-forming block. The block copolymers formed micelle-like aggregates with critical association concentration (cac) in the range of 1.54-2.57x10(-3)g/l in water. It was found that the size and cac of the aggregates depended on the hydrophobic block length and the ionic state of the PEI block. The aggregate size decreased and the cac increased, when the PLGA block length decreased and the PEI block was protonated. As a general program aimed at the development of a new nanoscopic drug carrier, the cellular uptake behavior of PEI-PLGA aggregates was compared with that of plain PLGA nanoparticles by using confocal microscopy. The results showed that PEI-PLGA aggregates was readily adsorbed onto the cell surfaces and translocated into the cytoplasm, implying their versatile applicability as a drug carrier.

Zinc oxide/polymethylmethacrylate composite microspheres by in situ suspension polymerization and their morphological study

Homogenously zinc oxide (ZnO)-dispersed polymethylmethacrylate (PMMA) composite microspheres were produced considering the interfacial characteristics of ZnO and PMMA in in situ suspension polymerization. The morphological observation with electron microscopes revealed that nano-sized ZnO particles were embedded homogeneously in the inner part of PMMA microspheres. Moreover, their spherical shape could be maintained to a large amount of ZnO in the PMMA phase. From this study, it was found that one of key requirements in the synthesis of inorganic/polymer composite microspheres was the enhanced interfacial compatibility between inorganic and polymer, which was achieved by treating the surface of inorganics hydrophobically and imparting conformational anchorage factor at inorganic interfaces.

Correlation between a Cutometer® and quantitative evaluation using Moire topography in age‐related skin elasticity

Background/purpose: As aging occurs, our skin gets more wrinkles, becomes drier and loses its elasticity. Validating the evaluation of skin elasticity is especially important, because it is not as visible as other signs of aging such as wrinkles. So it is needed that the method for measuring skin elasticity is able to reflect perception about the change of the skin state.

Self-aggregates of poly(2-hydroxyethyl aspartamide) copolymers loaded with methotrexate by physical and chemical entrapments

Amphiphilic copolymers based on poly(2-hydroxyethyl aspartamide) (PHEA) formed self-aggregates for the entrapment and release of methotrexate (MTX) by physical entrapment and chemical conjugation. In physical entrapment, MTX was partitioned into hydrophobic domains in self-aggregates of PHEA grafted with octadecyl chains (PHEA-C18) and the amount of the entrapped drug increased linearly by 3.39 mg per the degree of substitution of grafted octadecyl groups. The amphiphilic nature of the drug induced a large initial release in the buffer medium, irrespective of the amount of octadecyl chains. However, PEG-grafted PHEA-C18 copolymers conjugated with MTX, ConG, formed a micelle-like structure by self-association of the conjugates and suppressed the initial large release. The alkyl grafting lowered the CAC, meaning enhancement of aqueous stability. The release was accelerated in pH 10.0 by rapid hydrolysis of ester linkage by base-catalyzed cleavage, while it was significantly reduced at pH 5.0.

Identification of Mouse Prp19p as a Lipid Droplet-associated Protein and Its Possible Involvement in the Biogenesis of Lipid Droplets

Prp19p is an integral component of the heteromeric protein complex (the NineTeen complex) in the nucleus, and it is essential for the structural integrity of NineTeen complex and its subsequent activation of the spliceosome. We identified Prp19p, which has never been reported in relation to any function outside of the nucleus, as a member of proteins associated with lipid droplets. Down-regulation of Prp19p expression with RNA interference in 3T3-L1 cells repressed lipid droplet formation with the reduction in the level of expression of perilipin and S3-12. The levels of expression of SCD1 (stearoyl-CoA desaturase-1), DGAT-1 (acyl-CoA diacylglycerol acyltransferase-1), and glycerol-3-phosphate acyltransferase were also reduced in Prp19p down-regulated cells, and a significant decrease in triglycerides was observed. Unlike perilipin, which is one of the most extensively studied lipid droplet-associated proteins, Prp19p is not essential for cAMP- and hormone-sensitive lipase-dependent lipolysis pathways, even though Prp19p is a component of the lipid droplet phospholipid monolayer, and down-regulation of Prp19p represses fat accretion significantly. These results suggest that Prp19p or Prp19-interacting proteins during lipid droplet biogenesis in adipocytes may be considered as another class of potential targets for attacking obesity and obesity-related problems.

Comparison of objective and sensory skin irritations of several cosmetic preservatives.

There are many cosmetic ingredients, such as preservatives and fragrances, known to elicit adverse effects. The aim of this study was to investigate the side‐effects of cosmetic preservatives, by evaluating objective and subjective skin irritation. The method comprised of 2 parts. In part 1, we tried to compare 24‐hr patch test results with the sensory irritation potential of several preservatives. In part 2, skin cumulative irritation test for 21 days and sensory irritation test were performed to compare various combinations of preservatives in 4 types of formulations. Our data showed that methylparaben, ethylparaben, propylparaben, butylparaben, phenoxyethanol (PE) and chlorphenesin (CPN) have similar objective skin irritation potential at the minimal inhibitory concentration of each preservative, but CPN has higher potential than other preservatives in subjective irritation. Sensory irritation of preservatives changed according to formulation type, and PE combined with CPN highly increased irritation. There was correlation between antimicrobial activity and skin objective irritation but not sensory irritation. Influence on skin sensory irritation varies with the combination of preservatives. Therefore, for the development of new preservatives and cosmetics, it is important to evaluate skin sensory irritation of preservatives used in cosmetic products according to the type of formulations.

The extract of Thujae occidentalis semen inhibited 5α-reductase and androchronogenetic alopecia of B6CBAF1/j hybrid mouse

BACKGROUND The conversion of testosterone to dihydrotestosterone; 5alpha-androstan-17beta-ol-3-one by 5alpha-reductase plays a crucial role in hair baldness and prostatomegaly. Recent approach showed specific inhibitors for 5alpha-reductase type 2 such as finasteride promoted hair growth in male pattern alopecia. OBJECTIVE In order to search for effective medicinal plant extracts applied topically for androgenetic alopecia, we screened natural plant extracts having inhibitory activities of 5alpha-reductase type 2 and demonstrated its biological function in androgen-related animal models. METHODS We evaluated the inhibition activities of numerous plant extracts by contact cell based metabolic method using a stable HEK 293 cell line expressing human 5alpha-reductase (type 2). To elucidate the biological activity in vivo, the Thujae occidentalis semen (TOS) extract was topically applied to fuzzy rat and androchronogenetic alopecia (AGA) mouse, respectively. The secreted sebum and the size of sebaceous glands of fuzzy rat were measured after 6 weeks. Also, after the topical treatment with TOS extract and androgen receptor antagonist (cyproterone acetate) simultaneously with subcutaneous injection of testosterone (1 mg/mice/day), hair loss patterns of female B6CBAF1/j hybrid mouse were observed. RESULTS TOS extract showed higher inhibition activity of 5alpha-reductase type 2(IC(50) value=2.6 microg/ml) than that of gamma-linolenic acid, but lower than that of finasteride. When applied to fuzzy rat, the amount of sebum and sebaceous gland size decreased remarkably. In AGA model, alopecia degrees of two groups, treated with TOS extract (P<0.015) or cyproterone acetate (P<0.01), were lower than that of vehicle (propylene glycol:ethanol=7:3) and there was no difference between above two groups. CONCLUSION We have demonstrated the inhibitory activity of TOS extract for 5alpha-reductase type 2 and its biological action in two animal models, suggesting that TOS extract would be used as an effective agent for male pattern baldness by modifying androgen conversion.

Intracellular drug delivery using poly(d,l-lactide-co-glycolide) nano- particles derivatized with a peptide from a transcriptional activator protein of HIV-1

Biodegradable poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles were derivatized with Tat49−57 peptide, which is the protein transduction domain from the transcriptional activator Tat protein of human immunodeficiency virus type-1 (HIV-1). The Tat49−57 peptide-modified PLGA nanoparticles, with a mean diameter of ca. 238 nm, was effectively adsorbed on to the membrane of HaCaT cells and delivered into the nuclei without cytotoxicity.

Comparison and correlation between stinging responses to lactic acid and bioengineering parameters

In evaluating the safety of a novel cosmetic product or a new chemical, it is important to assess susceptible population. One group of subjects is known to stingers who are more likely to experience sensory effects such as stinging and burning after contacting with cosmetics. The purpose of the study is to measure skin biophysical parameters noninvasively in stingers and non‐stingers and to see their correlations with stinging responses. 298 women were evaluated by modified lactic acid stinging test with 5% lactic acid solution rather than classic 10% solution because of strong reaction in Asian populations. Transepidermal water loss (TEWL), skin hydration, sebum content, and pH were measured using the bioengineering instruments in an environment‐controlled room. Correlations between stinging responses and skin biophysical parameters were statistically analysed. There was a positive correlation between stinging responses and TEWL evaluation. However, no correlations was observed between stinging responses and other parameters such as skin hydration, sebum content, and pH. Our data indicate that there is a relationship between the degree of stinging and the skin barrier function. However, we believe that various additional studies are necessary to characterize skin of stingers and the pathogenesis.

Stabilization of papain and lysozyme for application to cosmetic products

For cosmetic applications, papain or lysozyme was conjugated to a soluble biopolymer produced by Schizophyllum commune. Stability of the conjugated enzymes were significantly enhanced, such that more than 90% of the initial activity remained after a month storage at 45 °C, even in a cosmetic formulation including various oils and surfactants. Cosmetic lotion containing 1% papain conjugate was more effective in exfoliating stratum corneum of skin than the lotion containing 5% lactic acid, one of the popular exfoliating agents.