Salt Effect Engineering Single Fe-N2P2-Cl Sites on Interlinked Porous Carbon Nanosheets for Superior Oxygen Reduction Reaction and Zn-Air Batteries.

Developing efficient metal-nitrogen-carbon (M-N-C) single-atom catalysts for oxygen reduction reaction (ORR) is significant for the widespread implementation of Zn-air batteries, while the synergic design of the matrix microstructure and coordination environment of metal centers remains challenges. Herein, a novel salt effect-induced strategy is proposed to engineer N and P coordinated atomically dispersed Fe atoms with extra-axial Cl on interlinked porous carbon nanosheets, achieving a superior single-atom Fe catalyst (denoted as Fe-NP-Cl-C) for ORR and Zn-air batteries. The hierarchical porous nanosheet architecture can provide rapid mass/electron transfer channels and facilitate the exposure of active sites. Experiments and density functional theory (DFT) calculations reveal the distinctive Fe-N2P2-Cl active sites afford significantly reduced energy barriers and promoted reaction kinetics for ORR. Consequently, the Fe-NP-Cl-C catalyst exhibits distinguished ORR performance with a half-wave potential (E1/2) of 0.92 V and excellent stability. Remarkably, the assembled Zn-air battery based on Fe-NP-Cl-C delivers an extremely high peak power density of 260 mW cm-2 and a large specific capacity of 812 mA h g-1, outperforming the commercial Pt/C and most reported congeneric catalysts. This study offers a new perspective on structural optimization and coordination engineering of single-atom catalysts for efficient oxygen electrocatalysis and energy conversion devices.

Carbon-Based Electron Buffer Layer on ZnOx -Fe5 C2 -Fe3 O4 Boosts Ethanol Synthesis from CO2 Hydrogenation.

The conversion of CO2 into ethanol with renewable H2 has attracted tremendous attention due to its integrated functions of carbon elimination and chemical synthesis, but remains challenging. The electronic properties of a catalyst are essential to determine the adsorption strength and configuration of the key intermediates, therefore altering the reaction network for targeted synthesis. Herein, we describe a catalytic system in which a carbon buffer layer is employed to tailor the electronic properties of the ternary ZnOx -Fe5 C2 -Fe3 O4 , in which the electron-transfer pathway (ZnOx →Fe species or carbon layer) ensures the appropriate adsorption strength of -CO* on the catalytic interface, facilitating C-C coupling between -CHx * and -CO* for ethanol synthesis. Benefiting from this unique electron-transfer buffering effect, an extremely high ethanol yield of 366.6 gEtOH kgcat -1 h-1 (with CO of 10 vol % co-feeding) is achieved from CO2 hydrogenation. This work provides a powerful electronic modulation strategy for catalyst design in terms of highly oriented synthesis.

Reinforced atomically dispersed FeNC catalysts derived from petroleum asphalt for oxygen reduction reaction.

Massive production of efficient, durable, and low-cost electrocatalysts toward oxygen reduction reaction (ORR) is urgently desired for the development of energy storage and conversion devices. In this study, a facile and cost-effective strategy is proposed for the scalable synthesis of atomically dispersed FeNC derived from petroleum asphalt (FeNC@PA) as a reinforced catalyst for ORR. The FeNC@PA is fabricated through a layer-by-layer cladding template and subsequent pyrolysis method. Intercalating appropriate amount of petroleum asphalt not only improves the graphitic degree to reinforce the atomic Fe-Nx active sites, but also increases mass yield of the catalyst (~220%) compared with the FeNC counterpart. Serving as an ORR electrocatalyst, the optimized FeNC@PA-1:4 provides almost a four-electron transfer pathway (3.96) and exhibits superior electrocatalytic activity with a half-wave potential (E1/2) of 0.90 V to the commercial Pt/C catalyst (E1/2 = 0.86 V), as well as promoted durability and methanol tolerance in alkaline medium. Moreover, the zinc-air battery based on FeNC@PA-1:4 cathode delivers a high power density of 166.7 mW cm-2. This work may help the massive production of robust atomically dispersed non-noble metal catalysts for ORR and provide a new avenue for the high value-added utilization of petroleum asphalt.

Curcumin loaded mixed micelles composed of Pluronic P123 and F68: preparation, optimization and in vitro characterization.

In this study, curcumin (Cur) loaded mixed micelles (Cur-PF), composed of Pluronic P123 (P123) and Pluronic F68 (F68), was prepared using the thin-film hydration method and evaluated in vitro. The preparation process was optimized with a central composite design (CCD). The average size of the mixed micelles was 68.2 nm, and the encapsulating efficiency for Cur was 86.93%, and 6.996% for drug-loading. Compared with the Cur propylene glycol solution, the in vitro release of Cur from Cur-PF presented the sustained-release property. The in vitro cytotoxicity assay showed that the IC(50) values on MCF-7 cells for Cur-PF and free Cur in DMSO solution were 5.04 µg/mL and 8.35 µg/mL, while 2.52 µg/mL and 8.27 µg/mL on MCF-7/ADR cells. It could be concluded from the results that P123/F68 mixed micelles might serve as a potential nanocarrier to improve the solubility and biological activity of Cur.

N-trimethyl chitosan chloride-coated liposomes for the oral delivery of curcumin.

The aims of this study were to design the formulation of curcumin (CUR) liposomes coated with N-trimethyl chitosan chloride (TMC) and to evaluate in vitro release characteristics and in vivo pharmacokinetics and bioavailability of TMC-coated CUR liposomes in rats. The structure of synthesized TMC was examined by infrared spectroscopy, with the presence of trimethyl groups, and by proton nuclear magnetic resonance spectroscopy, indicating the high degree of substitution quaternization (65.6%). Liposomes, composed of soybean phosphotidylcholine, cholestrol, and D-α-tocopheryl polyethylene glycol 1000 succinate, were prepared by a thin-film dispersion method. Characteristics of the CUR liposomes, including entrapment efficiency (86.67%), drug-loading efficiency (2.33%), morphology, particle size (221.4 nm for uncoated liposomes and 657.7 nm for TMC-coated liposomes), and zeta potential (-9.63 mV for uncoated liposomes and +15.64 mV for TMC-coated liposomes) were investigated. Uncoated CUR liposomes and TMC-coated CUR liposomes showed a similar in vitro release profile. Nearly 50% of CUR was released from liposomes, whereas 80% of CUR was released from CUR propylene glycol solution. CUR incorporated into TMC-coated liposomes exhibited different pharmacokinetic parameters and enhanced bioavailability (C(max) = 46.13 µg/L, t(1/2) = 12.05 hours, AUC = 416.58 µg/L·h), compared with CUR encapsulated by uncoated liposomes (C(max) = 32.12 µg/L, t(1/2) = 9.79 hours, AUC = 263.77 µg/L·h) and CUR suspension (C(max) = 35.46 µg/L, t(1/2) = 3.85 hours, AUC = 244.77 µg/L·h). In conclusion, oral delivery of coated CUR liposomes is a promising strategy for poorly water-soluble CUR.

Lung-targeted delivery system of curcumin loaded gelatin microspheres.

The purpose of the study is to design and evaluate curcumin loaded gelatin microspheres (C-GMS) for effective drug delivery to the lung. C-GMS was prepared by the emulsification-linkage technique and the formulation was optimized by orthogonal design. The mean encapsulation efficiency and drug loading of the optimal C-GMS were 75.5 ± 3.82 % and 6.15 ± 0.44%, respectively. The C-GMS presented a spherical shape and smooth surface with a mean particle diameter of 18.9 µm. The in vitro drug release behavior of C-GMS followed the first-order kinetics. The tissue distribution showed that the drug concentrations at lung tissue for the C-GMS suspension were significantly higher than those for the curcumin solution, and the Ce for lung was 36.19. Histopathological studies proved C-GMS was efficient and safe to be used as a passive targeted drug delivery system to the lung. Hence, C-GMS has a great potential for the targeted delivery of curcumin to the lung.

Eudragit® S100 coated calcium pectinate microspheres of curcumin for colon targeting.

Currently, colon-specific drug delivery systems have been investigated for drugs that can exert their bioactivities in the colon. In this study, Eudragit® S100 coated calcium pectinate microsphere, a pH-dependent and enzyme-dependent system, as colon-specific delivery carrier for curcumin was investigated. Curcumin-loaded calcium pectinate microspheres were prepared by emulsification-linkage method, and the preparation technology was optimised by uniform experimental design. The morphology of microspheres was observed under scanning electron microscopy. Interactions between drug and polymers were investigated with differential scanning calorimetry (DSC) and X-ray diffraction. In vitro drug release studies were performed in simulated colonic fluid in the presence of Pectinex Ultra SP-L or 1% (w/v) rat caecal content, and the results indicated that the release of curcumin was significantly increased in the presence of 1% (w/v) rat caecal contents. It could be concluded that Eudragit® S100 coated calcium pectinate microsphere was a potential carrier for colon delivery of curcumin.

Formulation optimization and bioavailability after oral and nasal administration in rabbits of puerarin-loaded microemulsion.

The main objective of the study was to investigate the efficacy of microemulsion (ME) to facilitate bioavailability of puerarin (PUE) after oral and nasal administration. The pseudo-ternary phase diagrams were constructed to screen the ME components and optimize the ME formulation. The optimized formulation for bioavailability assessment consisted of 20% Tween 80, 20% glycerin, and 1.6% ethyl oleate. The solubility (27.8 mg/mL) of PUE in ME was significantly improved compared to that (4.58 mg/mL) of crude PUE in water. The ME droplets were spherical with a mean particle diameter of 23.4 nm. After nasal (5 mg/kg) and oral (20 mg/kg) administration of a single dose of PUE as ME to fasted rabbits, the absolute bioavailability was 34.58% and 13.54%, respectively. It showed a shorter T(max) (0.75 h) for nasal administration than that (1.0 h) for oral administration of PUE-loaded ME. The C(max) of PUE-loaded ME was 0.55 µg/mL after nasal administration and 0.64 µg/mL after oral administration, respectively. The results showed that nasal administration might be a promising route to enhance the absorption of PUE in the form of ME.

Design and evaluation of osmotic pump-based controlled release system of Ambroxol Hydrochloride.

The purpose of the present study was to design and evaluate an osmotic pump-based drug delivery system for controlling the release of Ambroxol Hydrochloride (Amb). Citric acid, lactose and polyethylene glycol 6000 (PEG 6000) were employed as osmotic agents. Surelease EC containing polyethylene glycol 400 (PEG 400) controlling the membrane porosity was used as semi-permeable membrane. The formulation of tablet core was optimized by orthogonal design and evaluated by weighted mark method. The influences of the amount of PEG 400 and membrane thickness on Amb release were investigated. The optimal osmotic pump tablet (OPT) was evaluated in different release media and at different stirring rates. The major release power confirmed was osmotic pressure. The release of Amb from OPT was verified at a rate of approximately zero-order, and cumulative release percentage at 12?h was 92.6%. The relative bioavailability of Amb OPT in rabbits relative to the commercial sustained capsule was 109.6%. Our results showed that Amb OPT could be a practical preparation with a good prospect.

Lyotropic liquid crystal systems in drug delivery.

Lyotropic liquid crystal systems, such as reversed bicontinuous cubic and hexagonal mesophases, are attracting more and more attention because of their unique microstructures and physicochemical properties. Various bioactive molecules such as chemical drugs, peptides and proteins can be solubilized in either aqueous or oil phase and be protected from hydrolysis or oxidation. Furthermore, several studies have demonstrated sustained release of bioactive molecules from reversed cubic and hexagonal mesophases. This article gives an overview of recent advances and current status of reversed cubic and hexagonal mesophases, especially with respect to their preparation methods and applications in the field of drug delivery. In addition, potential problems and possible future research directions are highlighted.

Skin irritation and the inhibition effect on HSV-1 in vivo of penciclovir-loaded microemulsion.

The purpose of the present study was to investigate the skin irritation and pharmacodynamics of penciclovir-loaded microemulsion (PCV-ME). The formulation of PCV-ME was comprised of oleic acid (OA) (5%, w/w), Cremorphor EL (20%, w/w), ethanol (30%, w/w) and water (45%, w/w). PCV-ME presented as spherically shaped under transmission electron microscopy with an average diameter of 36.5 nm, and the solubility of PCV in microemulsion (ME) was 7.41 mg/g, almost 6 times that in water. Skin irritation test was performed in male guinea pigs, which demonstrated that no irritation effect was caused after single or multiple applications of PCV-ME. Likewise, male guinea pigs were employed as animal models which were infected with herpes simplex virus type 1 (HSV-1) in pharmacodynamics study. Real-time PCR was utilized to investigate the inhibition effect on HSV-1 exerted by commercial PCV-cream and PCV-ME. The results indicated that compared with commercial PCV-cream, PCV-ME could significantly inhibit the replication of HSV-1 in skin. In conclusion, PCV-ME could be a promising formulation which possessed the virtues of low irritation and high effectiveness.

Preparation, characterization, pharmacokinetics, and tissue distribution of curcumin nanosuspension with TPGS as stabilizer.

BACKGROUND: CUR is a promising drug candidate based on its good bioactivity, but use of CUR is potentially restricted because of its poor solubility and bioavailability. AIM: The aim of this study was to prepare an aqueous formulation of curcumin nanosuspension (CUR-NS) to improve its solubility and change its in vivo behavior. METHODS: CUR-NS was prepared by high-pressure homogenization method. Drug state in CUR-NS was evaluated by powder X-ray diffraction. Pharmacokinetics and biodistribution of CUR-NS after intravenous administration in rabbits and mice were studied. RESULTS: The solubility and dissolution of CUR in the form of CUR-NS were significantly higher than those of crude CUR. X-ray crystallography diffraction indicated that the crystalline state of CUR in nanosuspension was preserved. Pharmacokinetics and biodistribution results of CUR-NS after intravenous administration in rabbits and mice showed that CUR-NS presented a markedly different pharmacokinetic property as compared to the CUR solution. AUC(0-infinity) of CUR-NS (700.43 +/- 281.53 microg/mL, min) in plasma was approximately 3.8-fold greater than CUR solution (145.42 +/- 9.29 microg/mL min), and the mean residence time (194.57 +/- 32.18 versus 15.88 +/- 3.56 minutes) was 11.2-fold longer. CONCLUSION: Nanosuspension could serve as a promising intravenous drug-delivery system for curcumin.

Development of nanosuspension formulation for oral delivery of quercetin.

With the aim to enhance dissolution rate and oral bioavailability of quercetin, a poorly water-soluble drug, quercetin loaded nanosuspension (QT-NS) was fabricated by a tandem of nano-precipitation (NP) and high pressure homogenization (HPH) method. The formulation of nanosuspension was optimized by screening different stabilizers. Characterization of the original QT powder and QT-NS was carried out by transmission electron microscopy and scanning electron microscopy, X-ray diffraction (XRD) and dissolution tests. QT-NS presented a sphere-like shape under transmission electron microscopy with an average diameter of 393.5 nm and the zeta potential of -35.75 mV. XRD study suggested that QT was maintained in the state of crystalline during the fabrication process. The solubility of QT in nanosuspension was about 70-fold that of crude QT, and the dissolution of QT from QT-NS was increased as compared to that of the original QT powder. In plasma, QT-NS exhibited a significant reduction of clearance rate (2 +/- 0.1 mL/min vs. 15 +/- 4 mL/min) and increase of AUC(0-infinity), (53995 +/- 4126 microg/mL x min versus 3470 +/- 110.1 microg/mL x min) compared with the control suspension. Our results showed that the developed nanosuspension formulation had a great potential as a possible formulation of the poorly water-soluble QT to enhance the bioavailability.

[Preparation and characterization of curcumin loaded gelatin microspheres for lung targeting].

OBJECTIVE: To study the preparation technology and physicochemical characterization of curcumin loaded gelatin microspheres for lung targeting. METHODS: Curcumin loaded gelatin microspheres for lung targeting were prepared by the emulsion crosslinking method, and the preparation technology was optimized by orthogonal experimental design with biodegradable gelatin as the carrier, liquid paraffin as the oil phase, span 80 as the emulsifier. RESULTS: The optimal curcumin loaded gelatin microspheres were global with smooth surface, 6.15% for the drug loading, 75.5% for the encapsulation efficiency. 86.6% of microspheres size was in the range of 5-30 microm. The release test in vitro showed that 50% of curcumin could release from gelatin microspheres in 22 h and 77% in 48 h. CONCLUSIONS: The preparation technology is good and stable, and the obtained microspheres can control the release of curcumin.

Microemulsion-based hydrogel formulation of penciclovir for topical delivery.

The purpose of this study was to investigate microemulsion-based hydrogel (MBH) as a topical delivery system for penciclovir. Topical delivery of penciclovir in the forms of microemulsion, MBH and the commercial cream was evaluated in vitro and in vivo. The results of permeation test in vivo in mice showed that compared with the commercial cream, MBH and microemulsion could significantly increase the permeation of penciclovir into both epidermis and dermis. Stability test showed that MBH stored at 4 degrees C for 3 months had no significant change in physicochemical properties. Skin irritation test in rabbit demonstrated that single application or multiple applications of MBH did not cause any erythema or edema, slight skin irritation for microemulsion. Microstructure changes of skins after administration observed under light microscope and scanning electron microscope (SEM) might result from the interaction of the ingredients of microemulsion with skins, which was related with the permeation enhancement of penciclovir. It can be concluded that the MBH could be a promising vehicle for topical delivery of penciclovir.

Development and evaluation of penciclovir-loaded solid lipid nanoparticles for topical delivery.

The objective of this investigation was to develop solid lipid nanoparticles (SLNs) of penciclovir and evaluate the potential of SLNs as the carrier of penciclovir for topical delivery. Penciclovir-loaded SLNs were prepared by a double (W/O/W) emulsion technique. The SLNs presented spherical with the mean diameter of 254.9 nm. The entrapment efficiency, drug loading and zeta potential were 92.40%, 4.62% and -25.0 mV, respectively. DSC study showed that penciclovir encapsulated in SLNs was in the amorphous form. The cumulative amount of penciclovir penetrated through excised rat skin from SLNs was more than 2-fold that of the commercial cream as a control at 12h after administration. There was no significant difference of penciclovir content deposited in epidermis between the cream and SLNs administrated for 2, 6 and 12h, while SLNs increased the cumulative uptake of penciclovir in dermis significantly at the same intervals. Microscopic pictures showed that the interaction between SLNs and the skin surface changed the apparent morphology of stratum corneum and broke the close conjugation of corneocyte layers, which was the possible reason that SLNs increased the permeation of penciclovir into skin dermis. It can be concluded from our study that SLNs provide a good skin targeting effect and may be a promising carrier for topical delivery of penciclovir.