Corrigendum: Biosynthesis, characterization, and antifungal activity of plant-mediated silver nanoparticles using Cnidium monnieri fruit extract.

[This corrects the article DOI: 10.3389/fmicb.2023.1291030.].

Biosynthesis, characterization, and antifungal activity of plant-mediated silver nanoparticles using Cnidium monnieri fruit extract.

The present study describes a novel method for green synthesis of silver nanoparticles using Cnidium monnieri (CM-AgNPs). Cnidium monnieri fruit is an excellent anti tinea drug that can be used externally to treat superficial fungal infections in the human body. The aqueous ethanolic extract of Cnidium monnieri fruit was prepared and employed in the synthesis of stable silver nanoparticles via biological reduction method. The synthesis conditions of CM-AgNPs was systematically optimized using Box-Behnken design. CM-AgNPs were well characterized by UV-spectroscopy and X-ray powder diffraction (XRD), and it was confirmed that the synthesized particles were AgNPs. The possible functional groups required for the reduction and stabilization of CM-AgNPs in the extract were identified through FTIR spectrum. The size of CM-AgNPs structure was confirmed to be approximately 44.6 nm in polydisperse spherical shape through scanning electron microscopy (SEM), transmission electron microscopy (TEM), and laser dynamic light scattering (DLS). Further, the minimum inhibitory concentration 90% (MIC90) ratios values of Cm-AgNPs against Trichophyton rubrum (7 d), T. mentagrophytes (7 d) and Candida albicans (24 h) were 3.125, 3.125, and 0.78125 µg/mL, respectively, determined by the broth micro dilution method. Finally, the result was concluded that the synthesized AgNPs could be further evaluated in large scale as a potential human topical antifungal agent.

A comparative study on the preparation and evaluation of solubilizing systems for silymarin.

Silymarin (SM) exhibits clinical efficacy in treating liver injuries, cirrhosis, and chronic hepatitis. However, its limited water solubility and low bioavailability hinder its therapeutic potential. The primary objective of this study was to compare the in vitro and in vivo characteristics of the four distinct SM solubilization systems, namely SM solid dispersion (SM-SD), SM phospholipid complex (SM-PC), SM sulfobutyl ether-ß-cyclodextrin inclusion complex (SM-SBE-ß-CDIC) and SM self-microemulsifying drug delivery system (SM-SMEDDS) to provide further insights into their potential for enhancing the solubility and bioavailability of SM. The formation of SM-SD, SM-PC, and SM-SBE-ß-CDIC was thoroughly characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and powder X-ray diffractometry (PXRD) techniques to analyze the changes in their microscopic structure, molecular structure, and crystalline state. The particle size and polydispersity index (PDI) of SM-SMEDDS were 71.6 ± 1.57 nm, and 0.13 ± 0.03, respectively. The self-emulsifying time of SM-SMEDDS was 3.0 ± 0.3 min. SM-SMEDDS exhibited an improved in vitro dissolution rate and demonstrated the highest relative bioavailability compared to pure SM, SM-SD, SM-PC, SM-SBE-ß-CDIC, and Legalon®. Consequently, SMEDDS shows promise as a drug delivery system for orally administered SM, offering enhanced solubility and bioavailability.

Synergy of Paired Brønsted-Lewis Acid Sites on Defects of Zr-MIL-140A for Methanol Dehydration.

As a common defect-capping ligand in metal-organic frameworks (MOFs), the hydroxyl group normally exhibits Brønsted acidity or basicity, but the presence of inherent hydroxyl groups in the MOF structure makes it a great challenge to identify the exact role of defect-capping hydroxyl groups in catalysis. Herein, we used hydroxyl-free MIL-140A as the platform to generate terminal hydroxyl groups on defect sites via a continuous post-synthetic treatment. The structure and acidity of MIL-140A were properly characterized. The hydroxyl-contained MIL-140A-OH exhibited 4.6-fold higher activity than the pristine MIL-140A in methanol dehydration. Spectroscopic and computational investigations demonstrated that the reaction was initiated by the respective adsorption of two methanol molecules on the terminal-OH and the adjacent Zr vacancy. The dehydration of the adsorbed methanol molecules then occurred in the Brønsted-Lewis acid site co-participated associative pathway with the lowest energy barrier.

Preparation and curing behaviour of microencapsulated curing agents for cold-mixed epoxy asphalt.

This study aimed to improve control over the curing behaviour of cold-mixed epoxy asphalt by using a microencapsulated curing agent (2-PZ@PC). Prepared through solvent evaporation, the 2-PZ@PC microcapsules had 2-phenylimidazole as the core material and polycarbonate as the shell material. The research examined the impact of core-shell mass ratio on microcapsule morphology and composition. Various equations, including the kinetics equation, Kissinger equation, Flynn-Wall-Ozawa, and Crane equations, were employed to assess the sustained release effect of 2-PZ@PC microcapsules on epoxy resin curing behaviour. Fluorescence microscopy and viscosity experiments were used to observe the release state of microcapsules and confirm the retardation phenomenon during construction. Optimal 2-PZ@PC microcapsules displayed a smooth spherical morphology and a maximum encapsulation rate of 32 wt% at a 1:1 core-shell ratio. The microencapsulated curing agent effectively regulated cold-mixed epoxy asphalt's curing behaviour, enhancing retention time control and application reliability.

Population pharmacokinetics and dosing optimization of unbound teicoplanin in Chinese adult patients.

Objectives: To develop a population pharmacokinetic (PopPK) model describing unbound teicoplanin concentrations in Chinese adult patients and perform Monte Carlo simulations to optimize the dosing regimens. Methods: The raw data for PopPK analysis in this study were collected from Chinese adult patients. A PopPK model of unbound teicoplanin was developed and Monte Carlo simulations were used to optimize the dosing regimens. The trough concentrations of unbound teicoplanin were targeted at 0.75 mg/L and 1.13 mg/L for most infection induced by Gram-positive bacteria and endocarditis or severe infections, respectively. Results: A total of 103 teicoplanin unbound concentrations were collected from 72 Chinese adult patients. A one-compartment pharmacokinetic model with first-order elimination was established. The typical values of clearance and the volume of distribution were 11.7 L/h and 811 L, respectively. The clearance and volume of distribution of unbound teicoplanin were positively correlated with estimated glomerular filtration rate (eGFR) and serum albumin concentrations, respectively. Dosing simulation results showed that standard dosing regimens were unable to meet the treatment needs of all patients, and the dosing regimen need optimize based on eGFR and serum albumin concentrations. The high eGFR and serum albumin concentration were associated with reduced probability of achieving target unbound trough concentrations. Conclusion: We successfully characterized the pharmacokinetics of unbound teicoplanin in Chinese adult patients. Importantly, we further highlight the importance of guiding dosing through unbound drugs. To achieve safe and effective treatment, the dosing regimens need to be adjusted according to eGFR and serum albumin concentrations.

Investigation of the soft carbon microstructure in silicon/carbon anodes for superior lithium storage.

It is essential to consider the controllable microstructure of soft carbon and its enhancement effect on the electrochemical performance of silicon (Si) active materials. In this study, a series of Si@mesocarbon microbead (Si@MCMB) composites were prepared using mesophase pitch as the soft carbon source to coat nano-Si. The results showed that the ordered carbon layer stacking of soft carbon increased slightly with increasing heat treatment temperature in the range of 800-1400 °C. The Si@MCMB composites at higher temperature had a turbostratic carbon layer texture with rich porosity and smaller specific surface area, and had good cycle stability and high rate performance. These results highlighted that the co-existing structure of turbostratic carbon arrays with abundant porosity from soft carbon, provided the electron/ion transfer channels, underwent Si alloy volume change and enhanced the mechanical stability. Importantly, the relationship between the capacity retention rate of the Si@MCMB anodes and the microstructural characteristics (carbon layer and porosity) of soft carbon was established, which provided effective guidance for the design of high-performance silicon/carbon (Si/C) anode materials.

Population pharmacokinetics and model-informed precision dosing of lamivudine in Chinese HIV-infected patients with mild and moderate impaired renal function.

BACKGROUND: Lamivudine is a first-line medication used for human immunodeficiency virus (HIV) treatment. To date, the population pharmacokinetics of lamivudine in Chinese HIV-infected adults have not been assessed. This study aimed to develop a population pharmacokinetic model for oral lamivudine in Chinese HIV-infected adults and to determine the optimal lamivudine dosage regimens. RESEARCH DESIGN AND METHODS: A total of 1113 samples, from 828 Chinese HIV-infected patients treated with lamivudine 300 mg every 24 hours, were pooled from two open-label, prospective clinical trials. A population pharmacokinetics analysis was performed using a nonlinear mixed-effects modeling method. A Monte Carlo simulation was conducted to optimize lamivudine dosing. RESULTS: A two-compartment model adequately described the population pharmacokinetics of lamivudine. The typical population estimate for apparent clearance was 28.3 L/h. Creatinine clearance was identified as a significant factor influencing apparent clearance. According to the Monte Carlo simulation, patients with creatinine clearance between 50 and 70 mL/min should receive lamivudine 200 mg every 24 h or 300 mg every 36 h, to achieve optimal lamivudine exposure. CONCLUSIONS: No obvious ethnic differences were observed in lamivudine pharmacokinetics between Chinese and Caucasian populations. Additionally, a model-informed dosage regimen is recommended for patients with impaired renal function.

Effect of Surface Property on the Release and Oral Absorption of Solid Sirolimus-Containing Self-microemulsifying Drug Delivery System.

The combination of self-microemulsifying drug delivery system (SMEDDS) and mesoporous silica materials favors the oral delivery of poorly water-soluble drugs (PWSD). However, the influence of the surface property of the mesopores towards the drug release and in vivo pharmacokinetics is still unknown. In this study, SBA-15 with hydroxyl groups (SBA-15-H), methyl groups (SBA-15-M), amino groups (SBA-15-A), or carboxyl groups (SBA-15-C) was combined with SMEDDS containing sirolimus (SRL). The diffusion and self-emulsifying of SMEDDS greatly improved the drug release over the raw SRL and SRL-SBA-15-R (R referred to as the functional groups). Results of drug absorption and X-ray photoelectron spectroscopy (XPS) showed strong hydrogen binding between SRL and the amino groups of SBA-15-A, which hindered the drug release and oral bioavailability of SRL-SMEDDS-SBA-15-A. The favorable release of SRL-SMEDDS-SBA-15-C (91.31 ± 0.57%) and SRL-SMEDDS-SBA-15-M (91.76 ± 3.72%) contributed to enhancing the maximum blood concentration (Cmax) and the area under the concentration-time curve (AUC0→48). In conclusion, the release of SRL-SMEDDS-SBA-15-R was determined by the surface affinity of the SBA-15-R and the interaction between the SRL molecules and the surface of SBA-15-R. This study suggested that the SMEDDS-SBA-15 was a favorable carrier for PWSD, and the surface property of the mesopores should be considered for the optimization of the SMEDDS-SBA-15.

Correction to: Preparation and Evaluation of Cubic Nanoparticles for Improved Transdermal Delivery of Propranolol Hydrochloride.

Xin Zhou is a co-corresponding author of this published article and the affiliation should read "Xin Zhou1, 3".

Preparation and Evaluation of Cubic Nanoparticles for Improved Transdermal Delivery of Propranolol Hydrochloride.

Transdermal drug delivery of propranolol hydrochloride (PRH) is promising for the treatment of infantile hemangioma (IH). Clinically used PRH hydrogel fails to reach the deep IH for complete recovery. In this study, the PRH-loaded cubic nanoparticles (CNPs) were prepared to promote the transdermal effect of PRH. A remote drug loading method was developed to prepare the PRH-CNPs. For the traditional passive drug loading method, the largest encapsulation efficiency (EE%) was around 50%. The remote drug loading was performed by increasing the pH of the mixture of blank CNPs and PRH solution. The optimal PRH-CNPs showed an EE% of 90.15 ± 2.44% at pH 8.5. The permeation of the PRH solution was poor while the PRH-CNPs showed greatly enhanced skin permeation. It was found that smaller-sized PRH-CNPs contributed to increased skin permeation and retention. In addition, the PRH-CNPs had higher cytotoxicity towards the EOMA cells when compared with the PRH solution. During storage for 1 month, the PRH-CNPs kept stable size distribution, pH, and EE%. In conclusion, results of this study suggested that the PRH-CNPs could be a potential candidate for the treatment of the IH by transdermal delivery.

Light-triggered OVA release based on CuS@poly(lactide-co-glycolide acid) nanoparticles for synergistic photothermal-immunotherapy of tumor.

The immunotherapy played a vital role in the treatment of metastatic tumor. To further enhance the effect of the immunotherapy, the combination of photothermal effect can not only eradicate the tumor cells by hyperthermia, but also improved the antigen release in vivo to achieve enhanced immune responses. In this study, a core-shell structured nanocomplex was developed by loading of ovalbumin (OVA) and copper sulfide nanoparticles (CuS-NPs) into the poly(lactide-co-glycolide acid) nanoparticles (PLGA-NPs). The CuS-NPs exhibited favorable photothermal effect, which significantly kill the 4T1 tumor cells in vitro. The photothermal effect of the CuS-NPs accelerated the OVA release, which led to higher levels of IL-6, IL-12 and TNF-α, and activation of CD8+ T cells. Both of the OVA-PLGA-NPs and CuS-NPs with NIR light irradiation contributed inhibited primary tumor while the growth of the distant tumors was not hindered. The irradiated CuS@OVA-PLGA-NPs exhibited a minimal primary tumor because of the combined effect of photothermal therapy and immunotherapy. Moreover, the irradiated CuS@OVA-PLGA-NPs showed the most extensive distribution of CD8+ T cells in the primary and distant tumor, which blocked the rise of the distant tumor. In conclusion, the CuS@OVA-PLGA-NPs presented as a promising strategy for metastatic tumor therapy.

Cationic nanoemulsions with prolonged retention time as promising carriers for ophthalmic delivery of tacrolimus.

Tacrolimus, also known as FK506, is a first-line drug for the topical treatment of immune-mediated inflammatory anterior ocular diseases (IIAODs). However, due to its limited water solubility, hydrophobic nature and relatively high molecular weight, topical application of FK506 features poor bioavailability. Numbers of formulations have been attempted to enhance the erratic bioavailability of FK506 through various techniques. But until now, none of them could satisfy the clinical needs completely. Here, a novel formulation of FK506, FK506-loaded cationic nanoemulsions (FK506 CNE), was developed to prolong the precorneal residence time of FK506, thereby enhancing the bioavailability of FK506 for IIAODs therapy. FK506 CNE was prepared by high-pressure homogenization, and its composition was screened and optimized by single-factor experiments. The FK506 CNE showed spherical morphology with a mean diameter of 178.8 ± 2.7 nm and a zeta potential of +25.6 ± 0.6 mV. Results from in vivo gamma scintigraphy studies proved that the precorneal residence time of FK506 CNE was significantly increased, compared with FK506-loaded neutral nanoemulsions (FK506 NE) and saline. The data of aqueous humor pharmacokinetic study in rabbits showed that the relative bioavailability of FK506 CNE was 1.68-fold and 1.77-fold of FK506 NE and the marketed FK506 eye drops (Talymus®), respectively. Finally, hematoxylin and eosin staining images and in vitro cytotoxicity data confirmed the safety of the FK506 CNE. Taking all these into consideration, we propose that FK506 CNE is a promising topical ophthalmic nanoformulation for the management of IIAODs.

Quantifying Land Use/Land Cover and Landscape Pattern Changes and Impacts on Ecosystem Services.

Based on satellite remote sensing image, GIS and Fragstats, this study modeled and calculated the dynamic changes of land use, land cover and landscape patterns in Guizhou Province, China, and calculated the changes of ecosystem service values (ESVs). The impacts of the evolution of landscape patterns on the ESVs were analyzed, and reasonable policy recommendations were made. The findings are as follows: (1) In the past two decades, the area of cropland and grassland has decreased; the area of water bodies, urban and rural, industrial and mining, and residential areas has increased; the area of forestland has increased first and then decreased. (2) The two major types of landscapes, cropland and grassland, are clearly being replaced by two land types, forest land and water bodies. (3) Overall, the degree of landscape aggregation and adjacency has decreased, and the landscape heterogeneity has increased. (4) The total amount of ESV in 2000, 2008, 2013 and 2017 was 2574 × 108 Yuan RMB, 2605 × 108 Yuan RMB, 2618 × 108 Yuan RMB and 2612 × 108 Yuan RMB, respectively. The changes of landscape patterns had important impacts on the ESVs. In order to solve the problems caused by the increasingly prominent changes in the landscape patterns and improve the ESVs, it is necessary to rationally plan and allocate land resources, optimize the industrial structures, and develop effective regulatory policies.

Preparation and comparison of tacrolimus-loaded solid dispersion and self-microemulsifying drug delivery system by in vitro/in vivo evaluation.

This study aimed to compare the dissolution and the intestinal absorption of tacrolimus in self-microemulsifying drug delivery system (SMEDDS) and solid dispersion (SD). Poloxamer 188 SD was prepared by the combination of the solvent evaporation method and the freeze drying method. Hydroxypropyl methylcellulose (HPMC) SD was prepared by the solvent evaporation method combined with the vacuum drying method. The formation of SD was confirmed by SEM images which showed new solid phases. The SMEDDS was composed of oil (Labrafil M1944 CS 28%), surfactant (Cremophor EL 48%) and co-surfactant (Transcutol P 24%). The self microemulsion formed by the SMEDDS upon aqueous media had spherical droplets with a hydrodynamic size of 46.0±3.2nm. The dissolution of tacrolimus from SD and SMEDDS was performed in sink and non-sink conditions with various pH. As revealed by the DSC and FT-IR, the tacrolimus was molecularly or amorphously dispersed in the SMEDDS and SD. The in vivo intestinal absorption study in rats showed that both SMEDDS and SD improved the absorption of tacrolimus over the raw tacrolimus while the SMEDDS exhibited lower absorption rate constant (Ka) and apparent permeability coefficients (Papp) than the SD. The self-prepared SD with poloxamer 188 or HPMC had comparable intestinal absorption as compared with Prograf®. The tacrolimus-loaded SMEDDS and SD would be further compared by in vivo pharmacokinetic study.

Effect of CYP3A4 and CYP3A5 Genetic Polymorphisms on the Pharmacokinetics of Sirolimus in Healthy Chinese Volunteers.

BACKGROUND: Sirolimus is a promising immunosuppressive drug for preventing the rejection of organ transplants. However, inter-individual variability in sirolimus pharmacokinetics causes adverse drug reactions, compromising therapeutic efficacy. Sirolimus is primarily metabolized by cytochrome CYP3A4 and CYP3A5. This study aimed to clarify the effect of CYP3A genetic polymorphisms, including the CYP3A4*1G and CYP3A5*3 polymorphisms, on the pharmacokinetics of sirolimus. METHODS: Thirty-one healthy Chinese volunteers were included in this study. Their genotypes were determined using the Sequenom MassARRAY iPLEX platform, and blood sirolimus concentrations at different time points were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters were calculated using WinNonlin version 5.2 software. RESULTS: The allele frequencies of CYP3A4*1G and CYP3A5*3 were 25.8% and 71.0%, respectively. In CYP3A4*1G carriers (n = 13), the area under the curve AUC0-144, AUC0-∞, and Cmax were significantly lower (P < 0.05) than CYP3A4*1/*1 homozygous subjects (n = 18). Briefly, the AUC0-144, AUC0-∞, and Cmax of *1G/*1G carrier were 315.2 ± 91.5, 372.0 ± 108.2, and 10.2 ± 1.6 ng/mL, respectively, and those of *1/*1 G*1/*1 G carrier were 440.8 ± 130.6, 537.4 ± 167.5, and 13.7 ± 4.3, respectively, whereas those of CYP3A4*1/*1 homozygous subjects were 540.2 ± 150.6, 626.6 ± 166.9, and 19.8 ± 7.5 ng/mL, respectively. In CYP3A5-nonexpressing subjects (*3/*3 homozygous carriers, n = 15), the AUC0-144 and Cmax were 549.6 ± 137.9 and 19.9 ± 7.9 ng/mL, respectively, and were significantly higher (P < 0.05) than the values in CYP3A5-expressing subjects (*1/*1homozygous carrier, n = 2; 314.2 ± 129.3 and 10.3 ± 2.2 ng/mL; *1/*3 heterozygous carrier, n = 15; 440.2 ± 146.3 and 14.6 ± 5.1 ng/mL, respectively). CONCLUSIONS: CYP3A4 and CYP3A5 genetic polymorphisms are important factors affecting pharmacokinetic parameters of sirolimus. Our data support the monitoring of blood sirolimus concentrations, especially in CYP3A5*1 and CYP3A4*1 G carriers, to ensure accurate dosing in the clinical setting.

Development of solidified self-microemulsifying delivery systems with enhanced stability of sirolimus and extended release.

The application of sirolimus (SRL) as immunosuppressive agent is hampered by its poor water solubility and narrow therapeutic range. The self-microemulsifying drug delivery system (SMEDDS) succeeded in improving the solubility of SRL in our previous work. In this study, the formulation of the SMEDDS was further optimized by investigating the influence of the excipients including the media, antioxidant and organic acid. It was demonstrated that addition of 0.20% of citric acid in SMEDDS most efficiently promoted the stability of SRL under high temperature (40±2°C), high humidity (relative humidity 90±5%) or strong light irradiation (4500±500lx). SMEDDS absorbed by microcrystalline cellulose (MCC) was mixed with hydroxypropyl methylcellulose (HPMC) to prepare tablets. The optimal formulation composed of 15% of HPMC 100 LV with hardness of 120N, which had a sustained release of 12h. Results of X-ray powder diffraction and differential scanning calorimetry demonstrated that SRL in the tablets was in amorphous or molecularly dispersed state. The SMEDDS-tablets presented as promising substrates for water insoluble drugs with enhanced stability and extended release.

[Effect of propranolol gel on infantile hemangiomas].

OBJECTIVE: To evaluate the efficacy and security of propranolol gel in treatment of Infantile hemangiomas. METHODS: 51 consecutive infants with hemangiomas from October 2010 to September 2011 in Department of General Surgery Fuzhou General Hospital of Nanjing Military Command were treated with propranolol hydrochloride 3% gel. Changes in hemangioma size, texture, color, tumor blood flow peak were recorded. RESULTS: The results were evaluated using Achauer system, responses of IHs to propranolol were considered scale I (poor) in 4 patient (17.24%), scale II (moderate) in 18 patients (24.14%), scale III (good) in 22 patients (44.83%) and scale IV (excellent) in 7 patients (13.79%). The response of superficial hemangiomas was significantly better than other hemangiomas (P < 0.05), and no significant differences in response among different primary sites (P > 0.05). CONCLUSIONS: Topical use of propranolol hydrochloride 3% gel is an effective option for superficial hemangiomas.