Electrolyte Design for High-Voltage Lithium-Metal Batteries with Synthetic Sulfonamide-Based Solvent and Electrochemically Active Additives.

Considering practical viability, Li-metal battery electrolytes should be formulated by tuning solvent composition similar to electrolyte systems for Li-ion batteries to enable the facile salt-dissociation, ion-conduction, and introduction of sacrificial additives for building stable electrode-electrolyte interfaces. Although 1,2-dimethoxyethane with a high-donor number enables the implementation of ionic compounds as effective interface modifiers, its ubiquitous usage is limited by its low-oxidation durability and high-volatility. Regulation of the solvation structure and construction of well-structured interfacial layers ensure the potential strength of electrolytes in both Li-metal and LiNi0.8Co0.1Mn0.1O2 (NCM811). This study reports the build-up of multilayer solid-electrolyte interphase by utilizing different electron-accepting tendencies of lithium difluoro(bisoxalato) phosphate (LiDFBP), lithium nitrate, and synthetic 1-((trifluoromethyl)sulfonyl)piperidine. Furthermore, a well-structured cathode-electrolyte interface from LiDFBP effectively addresses the issues with NCM811. The developed electrolyte based on a framework of highly- and weakly-solvating solvents with interface modifiers enables the operation of Li|NCM811 cells with a high areal capacity cathode (4.3 mAh cm-2) at 4.4 V versus Li/Li+.

Acid- and Gas-Scavenging Electrolyte Additive Improving the Electrochemical Reversibility of Ni-Rich Cathodes in Li-Ion Batteries.

In view of their high theoretical capacities, nickel-rich layered oxides are promising cathode materials for high-energy Li-ion batteries. However, the practical applications of these oxides are hindered by transition metal dissolution, microcracking, and gas/reactive compound formation due to the undesired reactions of residual lithium species. Herein, we show that the interfacial degradation of the LiNi0.9CoxMnyAlzO2 (NCMA, x + y + z = 0.1) cathode and the graphite (Gr) anode of a representative Li-ion battery by HF can be hindered by supplementing the electrolyte with tert-butyldimethylsilyl glycidyl ether (tBS-GE). The silyl ether moiety of tBS-GE scavenges HF and PF5, thus stabilizing the interfacial layers on both electrodes, while the epoxide moiety reacts with CO2 released by the parasitic reaction between HF and Li2CO3 on the NCMA surface to afford cyclic carbonates and thus suppresses battery swelling. NCMA/Gr full cells fabricated by supplementing the baseline electrolyte with 0.1 wt % tBS-GE feature an increased capacity retention of 85.5% and deliver a high discharge capacity of 162.9 mAh/g after 500 cycles at 1 C and 25 °C. Thus, our results reveal that the molecular aspect-based design of electrolyte additives can be efficiently used to eliminate reactive species and gas components from Li-ion batteries and increase their performance.

Paclitaxel-incorporated nanoparticles of hydrophobized polysaccharide and their antitumor activity.

The aim of this study was to characterize paclitaxel-incorporated polysaccharide nanoparticles and evaluate their antitumor activity in vitro and in vivo. Pullulan was hydrophobically modified using acetic anhydride to make the paclitaxel-incorporated nanoparticles. Pullulan acetate (PA) was used to encapsulate paclitaxel using the nanoprecipitation method. The particles had spherical shapes under electron microscopy with sizes <100 nm. The sizes of paclitaxel-incorporated nanoparticles increased to >100 nm, and higher drug feeding induced higher particle size and drug content. Initial drug burst release was observed until 2 days and then the drug was continuously released over 1 week. Intrinsic cytotoxicity of empty PA nanoparticles was tested with RAW264.7 macrophage cells for biocompatibilty. The viability of RAW264.7 cells was >93% at all concentrations of empty PA nanoparticles, indicating that the PA nanoparticles are not acutely cytotoxic to normal human cells. The nanoparticles showed lower antitumor activity in vitro against HCT116 human colon carcinoma cells than that of paclitaxel itself, indicating the sustained release properties of nanoparticles. An in vivo study using HCT116 human colon carcinoma-bearing mice showed that paclitaxel-incorporated PA nanoparticles reduced tumor growth more than that of paclitaxel itself. These results indicate that PA paclitaxel-incorporated nanoparticles are a promising candidate for antitumor drug delivery.

Antitumor effect of adriamycin-encapsulated nanoparticles of poly(DL-lactide-co-glycolide)-grafted dextran.

In this study, we prepared adriamycin (ADR)-encapsulated core-shell type nanoparticles of a poly(DL-lactide-co-glycolide) (PLGA) grafted-dextran (DexLG) copolymer and evaluated its antitumor activity in vitro and in vivo. The particle size of ADR-encapsulated DexLG nanoparticles was around 50-200 nm and the morphology was spherical shapes at transmission electron microscopy (TEM) observation. Since reconstitution of lyophilized nanoparticles is essential to practical use in vivo, ADR-encapsulated DexLG nanoparticles were lyophilized and reconstituted them into deionized water. Although reconstitution process caused increase of particle size, drug release behavior of nanoparticles was not significantly changed before and after reconstitution process. The ADR-encapsulated DexLG nanoparticles were less cytotoxic than free ADR plus empty nanoparticles at in vitro, while empty DexLG nanoparticles did not significantly affect cell viability. Even if free ADR plus empty nanoparticles are most effective to inhibit tumor growth at tumor-induced animal model using CT-26 cells, ADR-encapsulated DexLG nanoparticles showed increased survivability of mice. These results indicated that ADR-encapsulated DexLG nanoparticles are promising vehicles for antitumor drug delivery.

Cytotoxicity of amphotericin B-incorporated polymeric micelles composed of poly(DL-lactide-co-glycolide)/dextran graft copolymer.

In this study, we prepared amphotericin B (AmpB)-encapsulated polymeric micelle of poly(DL-lactideco-glycolide) (PLGA) grafted-dextran (DexLG) copolymer for the cytotoxicity test. The average particle size of AmpB-encapsulated DexLG polymeric micelles was around 30 approximately 70 nm and their morphology showed spherical shapes. Since aggregation states of AmpB are related to intrinsic cytotoxicity, prevention of AmpB aggregation in aqueous solution will provide low cytotoxicity and increased antimicrobial activity for the infectious disease. At UV/VIS spectrum measurement, polymeric micelle prepared from methanol/water mixture (method B) showed a monomeric state of AmpB while polymeric micelle prepared from DMSO (method A) showed an aggregated state. During the hemolysis activity test, polymeric micelle from method B showed reduced hemolysis activity compared to AmpB itself and polymeric micelle from method A. These results indicated that AmpB-incorporated polymeric micelle prepared from methanol/water mixture has low cytotoxicity and favorable antimicrobial activity.

Amphotericin B-incorporated polymeric micelles composed of poly(d,l-lactide-co-glycolide)/dextran graft copolymer.

In this study, we prepared amphotericin B (AmpB)-encapsulated polymeric micelle of poly(d,l-lactide-co-glycolide) (PLGA) grafted-dextran (DexLG) copolymer and characterized its physicochemical properties in vitro. The average particle size of AmpB-encpasulated DexLG polymeric micelles was around 30-150nm while particle size of empty polymeric micelles was below 100nm according to the copolymer composition. The morphology of AmpB-encapsulated polymeric micelle of DexLG copolymer was spherical shapes at transmission electron microscopy (TEM) observation. At 1H NMR study, specific peaks of AmpB and DexLG copolymer was obtained at DMSO but specific peaks characterized to AmpB and PLGA was disappeared at D2O environment. These results indicated that AmpB was encapsulated into the micellar core of polymeric micelle. XRD results also support these results, indicating that specific crystal peaks of AmpB and broad peaks of DexLG copolymer were obtained but specific peaks of AmpB was disappeared at polymeric micelles while physical mixture of AmpB/empty polymeric micelles showed both specific peaks. Drug release rate was decreased according to the increase of drug contents and increase of PLGA component of DexLG copolymer. At the minimal inhibition concentration (MIC) study using Candida albicans, AmpB-encapsulated polymeric micelle showed almost similar effectives on the growth inhibition of microorganisms. These showed that AmpB-encapsulated polymeric micelle of DexLG copolymer can be considered to potential antifungal agent carriers.

Doxorubicin release from core-shell type nanoparticles of poly(DL-lactide-co-glycolide)-grafted dextran.

In this study, we prepared core-shell type nanoparticles of a poly(DL-lactide-co-glycolide) (PLGA) grafted-dextran (DexLG) copolymer with varying graft ratio of PLGA. The synthesis of the DexLG copolymer was confirmed by 1H nuclear magnetic resonance (NMR) spectroscopy. The DexLG copolymer was able to form nanoparticles in water by self-aggregating process, and their particle size was around 50 nm approximately 300 nm according to the graft ratio of PLGA. Morphological observations using a transmission electron microscope (TEM) showed that the nanoparticles of the DexLG copolymer have uniformly spherical shapes. From fluorescence probe study using pyrene as a hydrophobic probe, critical association concentration (CAC) values determined from the fluorescence excitation spectra were increased as increase of DS of PLGA. 1H-NMR spectroscopy using D2O and DMSO approved that DexLG nanoparticles have core-shell structure, i.e. hydrophobic block PLGA consisted inner-core as a drug-incorporating domain and dextran consisted as a hydrated outershell. Drug release rate from DexLG nano-particles became faster in the presence of dextranase in spite of the release rate not being significantly changed at high graft ratio of PLGA. Core-shell type nanoparticles of DexLG copolymer can be used as a colonic drug carrier. In conclusion, size, morphology, and molecular structure of DexLG nanoparticles are available to consider as an oral drug targeting nanoparticles.

Adriamycin release from self-assembling nanospheres of poly(DL-lactide-co-glycolide)-grafted pullulan.

Poly(DL-lactide-co-glycolide)-graft pullulan (PuLG) was synthesized to produce a hydrophobically modified polysaccharide. Specific pullulan and poly(DL-lactide-co-glycolide) (PLGA) (abbreviated as PuLG) appeared in the peaks of the PuLG spectra on (1)H NMR spectroscopy, suggesting that PLGA was successively grafted to the pullulan backbone. PuLG nanospheres have a round shape with a particle size of about 75-150 nm. From the fluorescence excitation spectra in a fluorescence probe study, the critical association concentration (CAC) values were determined to be 0.017 g/l for PuLG-1, 0.0054 g/l for PuLG-2, and 0.0047 g/l for PuLG-3. The drug contents of the PuLG nanospheres were approximately 20-30% (w/w). As the drug contents of PuLG nanospheres increased, the drug release rate from nanospheres decreased. The drug release rate from PuLG nanospheres was delayed as the molecular weight of PuLG increased. PuLG copolymer with higher graft ratio of PLGA showed slower degradation rate rather than that with lower graft ratio. Since degradation rate of PuLG was taken over 1 month, drug release was governed by diffusion mechanism rather than degradation mechanism.