2D Metal-Oxide Nanosheets as a Homogeneous Li-Ion Flux Regulator for High-Performance Anodeless Lithium Metal Batteries.

The anodeless battery design has recently gained significant interest by eliminating the direct use of a thick lithium (Li) foil. However, it suffers from inhomogeneous Li+ flux, resulting in dendrite growth and a short cycling life. To address this, the exfoliation of layered-structure titanium oxide to 2D nanosheets (2DTiOx) is proposed to precisely control Li+ flux at the atomic scale by maximizing Li+ affinitive Ti sites. Compared to cells without these nanosheets, the Li|2DTiOx|Cu half-cell demonstrates stable cyclability over 900 cycles, with a Coulombic efficiency (CE) over 99% at 0.5 mA cm-2 and 0.5 mAh cm-2. Similarly, a long stable cycling life over 1500 h at 1.0-3.0 mA cm-2 is observed for a 2DTiOx-based symmetric cell containing a limited Li amount from electrodeposited Li metal (e-Li|2DTiOx|e-Li). The full cells (e-Li|2DTiOx||NCM811 and e-Li|2DTiOx||LFP) coupled with NCM811 and LFP cathodes showed a long cycle life of 400 cycles at 1.0 C and 0.5 C, respectively. The exceptional battery performance is attributed to the uniform Li disposition on the 2DTiOx electrode, emphasizing the crucial role of the exposed basal plane in 2DTiOx as an efficient atomic scale Li+ flux regulator. This strategy is expected to advance next-generation lithium metal batteries (LMBs) by highlighting the significance of Li+ affinity at the Ti sites of 2DTiOx nanosheets.

Construction and characterization of the Korean whole saliva proteome to determine ethnic differences in human saliva proteome.

As the first step to discover protein disease biomarkers from saliva, global analyses of the saliva proteome have been carried out since the early 2000s, and more than 3,000 proteins have been identified in human saliva. Recently, ethnic differences in the human plasma proteome have been reported, but such corresponding studies on human saliva in this aspect have not been previously reported. Thus, here, in order to determine ethnic differences in the human saliva proteome, a Korean whole saliva (WS) proteome catalogue indexing 480 proteins was built and characterized through nLC-Q-IMS-TOF analyses of WS samples collected from eleven healthy South Korean male adult volunteers for the first time. Identification of 226 distinct Korean WS proteins, not observed in the integrated human saliva protein dataset, and significant gene ontology distribution differences in the Korean WS proteome compared to the integrated human saliva proteome strongly support ethnic differences in the human saliva proteome. Additionally, the potential value of ethnicity-specific human saliva proteins as biomarkers for diseases highly prevalent in that ethnic group was confirmed by finding 35 distinct Korean WS proteins likely to be associated with the top 10 deadliest diseases in South Korea. Finally, the present Korean WS protein list can serve as the first level reference for future proteomic studies including disease biomarker studies on Korean saliva.

Enhanced dissolution and oral absorption of tacrolimus by supersaturable self-emulsifying drug delivery system.

A new Soluplus (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer)-based supersaturable self-emulsifying drug delivery system (S-SEDDS) was formulated to enhance oral absorption of tacrolimus (FK506) with minimal use of oil, surfactant, and cosurfactant. A high payload supersaturable system (S-SEDDS) was prepared by incorporating Soluplus, as a precipitation inhibitor, to SEDDS consisting of Capmul MCM, Cremophor EL, and Transcutol (FK506:vehicle:Soluplus =1:15:1). In vitro dissolution profile and in vitro pharmacokinetic aspect of S-SEDDS in rats were comparatively evaluated with those of conventional SEDDS formulas containing four times greater content of vehicle components (FK506:vehicle =1:60). Both formulations formed spherical drug-loaded microemulsion <70 nm in size when in contact with aqueous medium. In an in vitro dissolution test in a nonsink condition, the amphiphilic polymer noticeably retarded drug precipitation and maintained >80% of accumulated dissolution rate for 24 hours, analogous to that from conventional SEDDS. Moreover, pharmacokinetic parameters of the maximum blood concentration and area under the curve from S-SEDDS formula in rats were not statistically different (P>0.05) than those of conventional SEDDS. The results suggest that the Soluplus-based supersaturable system can be an alternative to achieve a comparable in vitro dissolution profile and in vivo oral absorption with conventional SEDDS, with minimal use of vehicle ingredients.

A rapid and sensitive method to determine tacrolimus in rat whole blood using liquid-liquid extraction with mild temperature ultrasonication and LC-MS/MS.

Tacrolimus (TAC) is an immunosuppressant widely used in organ transplantation, but its extremely low aqueous solubility causes poor intestinal absorption. There have been efforts to develop an alternative TAC formulation with an improved dissolution rate and oral bioavailability (BA), and the development of a rapid and sensitive analytical method for its in vivo pharmacokinetic study is an essential prerequisite. Thus, here, we develop a novel method to determine TAC in rat whole blood based on liquid chromatography and tandem mass spectrometry, and liquid-liquid extraction (LLE) with mild temperature ultrasonication. For rapid and efficient separation of TAC from other hydrophobic compounds, a C8 column was chosen with isocratic mobile phase elution. With the help of the high specificity and the high sensitivity of multiple reaction monitoring in positive ion mode, the present method showed good performance including specificity, linearity (r(2) ≥ 0.996 within 1-200 ng/mL), sensitivity (the lower limit of quantitation at 1 ng/mL), intra- and inter-day accuracy (88.7-104.5 %) and precision (≤10.3 %), and recovery (94.7-102.6 %). Also, the stability of TAC and ascomycin, the internal standard, in rat whole blood was confirmed before and after the sample preparation. The validated method was satisfactorily applied to a pharmacokinetic study to determine TAC in rat whole blood following oral administration of the marketed product (Prograf(®), Astellas Pharma). In the present study, LLE with mild temperature ultrasonication was successfully expanded to the determination of a drug from whole blood or plasma for the first time. Therefore, the present method can contribute to the rapid in vivo evaluation of novel TAC formulations, and will be able to contribute to the development of TAC formulations with a higher dissolution rate and a higher BA.

Improved oral absorption of tacrolimus by a solid dispersion with hypromellose and sodium lauryl sulfate.

A novel surfactant-incorporated hydroxypropyl methylcellulose (HPMC) solid dispersion (SD) system was constructed in order to facilitate the release rate and oral absorption of tacrolimus (FK506), a poorly water-soluble immunosuppressant. Several emulsifiers including sodium lauryl sulfate (SLS), as drug release promotors, were employed with HPMC to fabricate SD using the solvent wetting method. The solid state characteristics using differential scanning calorimetry and X-ray powder diffraction, revealed that FK506 was molecularly distributed within all dispersions in amorphous form. The dissolution rates of FK506 in SLS-incorporated SDs were much higher than those in SDs prepared with HPMC alone, and even with stearoyl polyoxyl-32 glycerides or tocopheryl polyethylene glycol 1000 succinate. In particular, the greatest dissolution enhancement was obtained from the SD consisting of the drug, HPMC, and SLS in a weight ratio of 1:1:3, providing a 50-fold higher drug concentration within 15 min, compared with HPMC SD. In vivo absorption study in rats demonstrates that the optimized formula remarkably increased the oral absorption of FK506, providing about 4.0-fold greater bioavailability (p<0.05) compared with the marketed product (Prograf®, Astellas Pharma). These data suggest that a novel SLS/HPMC SD may be an advantageous dosage form of FK506, boosting the dissolution and absorption in gastrointestinal tract.

Multiresidue method for the quantitation of 20 pesticides in aquatic products.

As the consumption of aquatic products increased, the need for regulation of pesticide residues in aquatic products also emerged. Thus, in this study, a scheduled multiple reaction monitoring (sMRM) method employing a novel extraction and purification step based on QuEChERS with EDTA was developed for the simultaneous quantitation of 20 pesticides (alachlor, aldicarb, carbofuran, diazinon, dimethoate, dimethomorph, ethoprophos, ferimzone, fluridone, hexaconazole, iprobenfos, malathion, methidathion, methiocarb, phenthoate, phosalone, phosmet, phosphamidon, pirimicarb, and simazine) in aquatic products. Additionally, the present method was validated in the aspects of specificity, linearity (r ≥ 0.980), sensitivity (the limit of quantitation (LOQ) ≤ 5 ng/g), relative standard deviation, RSD (1.0% ≤ RSD ≤ 19.4%), and recovery (60.1% ≤ recovery ≤ 117.9%). Finally, the validated method was applied for the determination of the 20 pesticide residues in eel and shrimp purchased from local food markets. In the present study, QuEChERS with EDTA was successfully expanded to residual pesticide analysis for the first time. The present method could contribute to the rapid and successful establishment of the positive list system in South Korea.

Porous core/sheath composite nanofibers fabricated by coaxial electrospinning as a potential mat for drug release system.

This study focused on fabrication and characterization of porous core/sheath structured composite nanofibers with a core of blended salicylic acid (SA) and poly(ethylene glycol) (PEG) and a sheath of poly(lactic acid) (PLA) using a dual-capillary electrospinning system. Results of water contact angle measurements, field-emission scanning electron microscopy, and transmission electron microscopy indicated that feed rates of the core and sheath strongly affect the stability of the core/sheath structure and porous density of the composite nanofibers obtained, significantly influencing their SA release characteristics. At a lower ratio of feed rates of the core and the sheath, better stable core/sheath structures of nanofibers with higher porous density on the surface were formed resulting in a sustained release of SA over 5 days. Non-porous fibers showed a lower amount of drug release because the drug was embedded inside the core layer of the non-porous sheath layer. SA release from porous core/sheath nanofibers was described based on a one-dimensional Fickian diffusion mechanism, indicating that drug diffusion is a predominant factor in drug release. A cytotoxicity test suggested that the porous core/sheath nanofibers are non-toxic and support cell attachment. Therefore, this fiber mat may find application in the design of wound-healing patches with long-term activity.

Effect of electrospun non-woven mats of dibutyryl chitin/poly(lactic acid) blends on wound healing in hairless mice.

The aim of this study was to examine the proliferative ability of dibutyryl chitin (DBC) on scratch wounds in HaCaT keratinocytes and to evaluate the effect of nanoporous non-woven mat (DBCNFM) on skin wound healing in hairless mice using the advantages of DBCNFM, such as high porosity and high surface area to volume. The cell spreading activity of DBC was verified through a cell spreading assay in scratched human HaCaT keratinocytes. Scratch wound experiments showed that DBC notably accelerates the spreading rate of HaCaT keratinocytes in a dose dependent manner. The molecular aspects of the healing process were also investigated by hematoxylin & eosin staining of the healed skin, displaying the degrees of reepithelialization and immunostaining on extracellular matrix synthesis and remodeling of the skin. Topical application of DBCNFM significantly reduced skin wound rank scores and increased the skin remodeling of the wounded hairless mice in a dose dependent way. Furthermore, DBCNFM notably increased the expression of the type 1 collagen and filaggrin. These results demonstrate that DBC efficiently accelerates the proliferation of HaCaT keratinocytes and DBCNFM notably increases extracellular matrix synthesis on remodeling of the skin, and these materials are a good candidate for further evaluation as an effective wound healing agent.