Gene Reprogramming Armed Macrophage Membrane-Camouflaged Nanoplatform Enhances Bionic Targeted Drug Delivery to Solid Tumor for Synergistic Therapy.

Efficient drug delivery to solid tumors remains a challenge. HER2-positive (HER2+) tumors are an aggressive cancer subtype with a resistance to therapy, high risk of relapse, and poor prognosis. Although nanomedicine technology shows obvious advantages in tumor treatment, its potential clinical translation is still impeded by the unsatisfactory delivery and therapeutic efficacy. In this study, a gene reprogramming macrophage membrane-encapsulated drug-loading nanoplatform was developed for HER2+ cancer therapy based on the co-assembly of poly (lactic-co-glycolic acid) (PLGA) nanoparticles and engineered modified macrophage membranes. In this nanoplatform, near-infrared (NIR) fluorescent dye ICG or chemotherapeutic drug doxorubicin (DOX) was loaded into the PLGA cores, and an anti-HER2 affibody was stably expressed on the membrane of macrophages. In comparison to the nanoparticles with conventional macrophage membrane coating, the ICG/DOX@AMNP nanoparticles armed with anti-HER2 affibody showed excellent HER2-targeting ability both in vitro and in vivo. Small animal imaging studies confirmed the improved pharmacokinetics of drug delivery and specific distribution of the ICG/DOX@AMNPs in HER2+ tumors. Mechanistically, compared with DOX@NPs or DOX@MNPs nanoparticles, DOX@AMNPs exhibited synergistic inhibition of HER2+ cancer cells or mice tumor growth by inducing apoptosis and blocking the PI3K/AKT signaling pathway. Altogether, this study proposes a promising biomimetic nanoplatform for the efficient targeted delivery of chemotherapeutic agents to HER2+ tumors, demonstrating its great potential for solid tumor therapy.

Carbohydrate regulation response to cold during rhizome bud dormancy release in Polygonatum kingianum.

BACKGROUND: The rhizome of Polygonatum kingianum Coll. et Hemsl (P. kingianum) is a crucial traditional Chinese medicine, but severe bud dormancy occurs during early rhizome development. Low temperature is a positive factor affecting dormancy release, whereas the variation in carbohydrates during dormancy release has not been investigated systematically. Therefore, the sugar content, related metabolic pathways and gene co-expression were analysed to elucidate the regulatory mechanism of carbohydrates during dormancy release in the P. kingianum rhizome bud. RESULTS: During dormancy transition, starch and sucrose (Suc) exhibited opposing trends in the P. kingianum rhizome bud, representing a critical indicator of dormancy release. Galactose (Gal) and raffinose (Raf) were increased in content and synthesis. Glucose (Glc), cellulose (Cel), mannose (Man), arabinose (Ara), rhamnose (Rha) and stachyose (Sta) showed various changes, indicating their different roles in breaking rhizome bud dormancy in P. kingianum. At the beginning of dormancy release, Glc metabolism may be dominated by anaerobic oxidation (glycolysis followed by ethanol fermentation). After entering the S3 stage, the tricarboxylic acid cycle (TCA) and pentose phosphate pathway (PPP) were may be more active possibly. In the gene co-expression network comprising carbohydrates and hormones, HYD1 was identified as a hub gene, and numerous interactions centred on STS/SUS were also observed, suggesting the essential role of brassinosteroids (BRs), Raf and Suc in the regulatory network. CONCLUSION: We revealed cold-responsive genes related to carbohydrate metabolism, suggesting regulatory mechanisms of sugar during dormancy release in the P. kingianum rhizome bud. Additionally, gene co-expression analysis revealed possible interactions between sugar and hormone signalling, providing new insight into the dormancy release mechanism in P. kingianum rhizome buds.

Development and validation of a PCR-free nucleic acid testing method for RNA viruses based on linear molecular beacon probes.

BACKGROUND: RNA viruses periodically trigger pandemics of severe human diseases, frequently causing enormous economic losses. Here, a nucleic acid extraction-free and amplification-free RNA virus testing probe was proposed for the sensitive and simple detection of classical swine fever virus (CSFV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), based on a double-stranded molecular beacon method. This RNA virus probe contains two base sequences-a recognition strand that binds to the specific domain of CSFV N2 or SARS-CoV-2 N, with a fluorophore (FAM) labeled at the 5' end, and a complementary strand (CSFV-Probe B or SARS-CoV-2-Probe B), combined with a quencher (BHQ2) labeled at the 3' end. RESULTS: Using linear molecular beacon probe technology, the detection limit of the RNA virus probe corresponding to CSFV and SARS-CoV-2 were as low as 0.28 nM and 0.24 nM, respectively. After CSFV E2 and SARS-CoV-2 N genes were transfected into corresponding host cells, the monitoring of RNA virus probes showed that fluorescence signals were dramatically enhanced in a concentration- and time-dependent manner. These results were supported by those of quantitative (qRT-PCR) and visualization (confocal microscopy) analyses. Furthermore, CSF-positive swine samples and simulated SARS-CoV-2 infected mouse samples were used to demonstrate their applicability for different distributions of viral nucleic acids in series tissues. CONCLUSIONS: The proposed RNA virus probe could be used as a PCR-free, cost-effective, and rapid point-of-care (POC) diagnostic platform for target RNA virus detection, holding great potential for the convenient monitoring of different RNA viruses for early mass virus screening.

Paracoccus sediminilitoris sp. nov., isolated from a tidal flat sediment.

A novel marine Gram-stain-negative, non-spore-forming, motile, aerobic, coccoid or ovoid bacterium, designated as strain DSL-16T, was isolated from a tidal flat sediment on the East China Sea and characterized phylogenetically and phenotypically. Optimal growth of the strain occurred at 35 °C (range 4-40 °C), at pH 6 (range 5-11) and with 4 % (w/v) NaCl (range 1-14 %). The nearest phylogenetic neighbour was Paracoccusseriniphilus DSM 14827T (98.2 % 16S rRNA gene sequence similarity). The digital DNA-DNA hybridization value between strain DSL-16T and P. seriniphilus DSM 14827T was 19.5±2.2 %. The average nucleotide identity value between strain DSL-16T and P. seriniphilus DSM 14827T was 83.6 %. The sole respiratory ubiquinone was Q-10. The major polar lipids were phosphatidylmonomethylethanolamine (PME), phosphatidylglycerol (PG), phosphatidylcholine (PC), phosphatidylethanolamine (PE), diphosphatidyglycerol (DPG) and glycolipid (GL). The predominant cellular fatty acids of strain DSL-16T were C18 : 1ω7c, C18 : 0 and 11-methyl C18 : 1ω7c. The G+C content of the genomic DNA was 64.5 mol%. The combined genotypic and phenotypic data indicated that strain DSL-16T represents a novel species of the genus Paracoccus, for which the name Paracoccus sediminilitoris sp. nov. is proposed. The type strain is DSL-16T (=KCTC 62644T=MCCC 1K03534T).

Algoriphagus litoralis sp. nov., isolated from the junction between the ocean and a freshwater lake.

A Gram-stain negative, non-motile and short rod shaped bacterium, designated strain DSL-12T, was isolated from seawater of the East China Sea and characterised phylogenetically and phenotypically. Optimal growth was found to occur at 28 °C (range 4-40 °C), pH 7 (range 6-12) and with 3% (w/v) NaCl (range 0-8%). Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain DSL-12T is related to members of the genus Algoriphagus and shares high sequence similarities with Algoriphagus boritolerans DSM 17298T (97.6%) and Algoriphagus alkaliphilus DSM 22703T (97.6%). The 16S rRNA gene sequence identities between strain DSL-12T and other current members of the genus Algoriphagus were below 96.4%. The digital DNA-DNA hybridization values between strain DSL-12T and the type strains A. boritolerans DSM 17298T and A. alkaliphilus DSM 22703T were found to be 21.2 ± 2.4% and 20.2 ± 2.4%, respectively. The average nucleotide identity (ANI) values between strain DSL-12T and A. boritolerans DSM 17298T and A. alkaliphilus DSM 22703T were found to be 83.2% and 82.8%, respectively. The sole respiratory quinone was identified as MK-7. The major polar lipids were identified as phosphatidylethanolamine, diphosphatidylglycerol, one unidentified phospholipid and two unidentified lipids. The major fatty acids identified as were iso-C15:0, summed feature 8 (C18:1ω7c and/or C18:1ω6c), C16:0, summed feature 3 (C16:1ω7c and/or C16:1ω6c) and iso-C17:0. The G+C content of the genomic DNA was determined to be 43.3 mol%. The combined genotypic and phenotypic data indicate that strain DSL-12T represents a novel species of the genus Algoriphagus, for which the name Algoriphagus litoralis sp. nov. is proposed, with the type strain DSL-12T (= KCTC 62647T = MCCC 1K03536T).

A High Spatial Resolution Depth Sensing Method Based on Binocular Structured Light.

Depth information has been used in many fields because of its low cost and easy availability, since the Microsoft Kinect was released. However, the Kinect and Kinect-like RGB-D sensors show limited performance in certain applications and place high demands on accuracy and robustness of depth information. In this paper, we propose a depth sensing system that contains a laser projector similar to that used in the Kinect, and two infrared cameras located on both sides of the laser projector, to obtain higher spatial resolution depth information. We apply the block-matching algorithm to estimate the disparity. To improve the spatial resolution, we reduce the size of matching blocks, but smaller matching blocks generate lower matching precision. To address this problem, we combine two matching modes (binocular mode and monocular mode) in the disparity estimation process. Experimental results show that our method can obtain higher spatial resolution depth without loss of the quality of the range image, compared with the Kinect. Furthermore, our algorithm is implemented on a low-cost hardware platform, and the system can support the resolution of 1280 × 960, and up to a speed of 60 frames per second, for depth image sequences.

Pathogenic characteristics of an aggregated diarrhea event caused by Plesiomonas shigelloides from stream.

This study aimed to investigate the cause of a foodborne disease outbreak in Huzhou on August 14, 2023. Multiple enteropathogens were detected using FilmArray, and the pathogen was subsequently isolated and cultured from anal swabs of the cases and stream water. The isolated strains were identified using VITEK MS, and antimicrobial susceptibility test, pulsed field gel electrophoresis (PFGE) molecular typing, and whole genome sequencing (WGS) were performed on the isolates of Plesiomonas shigelloides. Gene annotation and sequence alignment were used to analyze the virulence genes and drug resistance genes of the strains. A phylogenetic tree was constructed based on single nucleotide polymorphism (SNP), and homology analysis was conducted to trace the origin of P. shigelloides. A total of 7 strains of P.shigelloides were isolated, with 3 from stream water and 4 from anal swabs. All 7 strains exhibited the same PFGE pattern and showed resistance to amikacin, trimethoprim-sulfamethoxazole, chloramphenicol, tetracycline, cefazolin, streptomycin, and florfenicol. The isolated strains carried the same resistance genes and virulence factors. In the sequences of the isolated strains from this outbreak, 11 mutation sites were detected. The phylogenetic tree based on SNP sites showed that these strains were homologous. This foodborne disease outbreak caused by P.shigelloides was the first reported in Huzhou. WGS can be used as a complementary method to PFGE for epidemiological investigations of disease outbreaks.

The Effectiveness of Traditional Chinese Medicine in Treating Malignancies via Regulatory Cell Death Pathways and the Tumor Immune Microenvironment: A Review of Recent Advances.

Traditional Chinese Medicine (TCM) has achieved high clinical efficacy in treating malignancies in recent years and is thus gradually becoming an important therapy for patients with advanced tumor for its benefits in reducing side effects and improving patients' immune status. However, it has not been internationally recognized for cancer treatment because TCM's anti-tumor mechanism is not fully elucidated, limiting its clinical application and international promotion. This review traced the mechanism of the TCM-mediated tumor cell death pathway and its effect on remodeling the tumor immune microenvironment, its direct impact on the microenvironment, its anti-tumor effect in combination with immunotherapy, and the current status of clinical application of TCM on tumor treatment. TCM can induce tumor cell death in many regulatory cell death (RCD) pathways, including apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis. In addition, TCM-induced cell death could increase the immune cells' infiltration with an anti-tumor effect in the tumor tissue and elevate the proportion of these cells in the spleen or peripheral blood, enhancing the anti-tumor capacity of the tumor-bearing host. Moreover, TCM can directly affect immune function by increasing the population or activating the sub-type immune cells with an anti-tumor role. It was concluded that TCM could induce a pan-tumor death modality, remodeling the local TIME differently. It can also improve the systemic immune status of tumor-bearing hosts. This review aims to establish a theoretical basis for the clinical application of TCM in tumor treatment and to provide a reference for TCM's potential in combination with immunotherapy in cancer treatment.

Population pharmacokinetics, dosing optimization and clinical outcomes of biapenem in patients with sepsis.

Introduction: Biapenem is a carbapenem antibiotic widely used in Asia, can be used for the treatment of adults and children with infections due to susceptible bacteria. Although biapenem is utilized in the treatment of a diverse range of bacterial infections, current pharmacokinetic data in the context of septic populations remain limited. Consequently, our research aims to evaluate the pharmacokinetics and efficacy of biapenem within a septic population to optimize biapenem therapy. Methods: In this study, we characterized the pharmacokinetics of biapenem in septic patients using a population pharmacokinetic (PPK) approach. The clinical PK data to develop the PPK model were obtained from 317 septic patients admitted to Nanjing Drum Tower Hospital between 2018 and 2022. All patients were randomized to the modeling and validation cohorts at a 3:1 ratio, with PPK modeling and validation performed utilizing the NONMEM software. Results: The model found to best describe the available data was a two-compartment PPK model with first-order elimination characterized by the parameters clearance (CL), central volume (V1), peripheral volume (V2), and intercompartmental clearance (Q). A covariate analysis identified that creatinine clearance (CLCR) was a significant covariate influencing biapenem CL, while blood urea nitrogen (BUN) was a significant covariate influencing biapenem Q. Accoding to the clinical outcome analyses, 70% of the time that the free antimicrobial drug concentration exceeds the MIC (fT >MIC) is associated with favourable clinical outcomes. The PPK model was then used to perform Monte Carlo simulations to evaluate the probability of attaining 70% fT >MIC. Conclusions: A final PPK model of biapenem was established for patients with sepsis. The current daily dosage regimen of 1.2 g may insufficient to achieve 70% fT >MIC in septic patients. The dosage regimen of 600 mg every 6 h appears to be the optimal choice.

7-Ethyl-10-hydroxycamptothecin proliposomes with a novel preparation method: optimized formulation, characterization and in-vivo evaluation.

CONTEXT: The proliposomes were used to solve the stability of the ordinary liposomes. OBJECTIVE: 7-ethyl-10-hydroxycamptothecin (SN-38) proliposomes for intravenous (i.v.) administration were prepared successfully by a new method. MATERIALS AND METHODS: SN-38 liposomes solution was reconstituting automatically from proliposomes on contact with the acetic acid buffer solution (0.2 M, pH 2.6). The formulation was optimized by the Box-Behnken design. The physicochemical characteristics of the SN-38 proliposomes were studied by scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The stability studies were also carried on. The FLU-HPLC system was served to study the concentration of SN-38 in the plasma of Sprague Dawley (SD) rats. RESULTS: The optimized formulation was SN-38: 0.03 g; Soybean phospholipid (SP): 0.6 g; dextrose: 3.00 g. The entrapment efficiency of the optimized formulation was >85% and the mean particle size was about 231 nm. The stability studies showed that SN-38 proliposomes were stable in dark at 20-25°C for 6 months at least. The pharmacokinetic parameters of i.v. administration demonstrated that the half-life of SN-38 loaded in the liposomes was prolonged in vivo. DISCUSSION AND CONCLUSION: The SN-38 proliposomes was prepared successful by the analysis of TEM, SEM, DSC and XRD, and SN-38 liposomes could be reconstituted on contact with the hydration medium. SN-38 liposomes circulated for a longer time in the blood circulating system than SN-38 solution, which contributed to maintaining the drug action.

Ongoing involvers and promising therapeutic targets of hepatic fibrosis: The hepatic immune microenvironment.

Hepatic fibrosis is often secondary to chronic inflammatory liver injury. During the development of hepatic fibrosis, the damaged hepatocytes and activated hepatic stellate cells (HSCs) caused by the pathogenic injury could secrete a variety of cytokines and chemokines, which will chemotactic innate and adaptive immune cells of liver tissue and peripheral circulation infiltrating into the injury site, mediating the immune response against injury and promoting tissue reparation. However, the continuous release of persistent injurious stimulus-induced inflammatory cytokines will promote HSCs-mediated fibrous tissue hyperproliferation and excessive repair, which will cause hepatic fibrosis development and progression to cirrhosis even liver cancer. And the activated HSCs can secrete various cytokines and chemokines, which directly interact with immune cells and actively participate in liver disease progression. Therefore, analyzing the changes in local immune homeostasis caused by immune response under different pathological states will greatly enrich our understanding of liver diseases' reversal, chronicity, progression, and even deterioration of liver cancer. In this review, we summarized the critical components of the hepatic immune microenvironment (HIME), different sub-type immune cells, and their released cytokines, according to their effect on the development of progression of hepatic fibrosis. And we also reviewed and analyzed the specific changes and the related mechanisms of the immune microenvironment in different chronic liver diseases.Moreover, we retrospectively analyzed whether the progression of hepatic fibrosis could be alleviated by modulating the HIME.We aimed to elucidate the pathogenesis of hepatic fibrosis and provide the possibility for exploring the therapeutic targets for hepatic fibrosis.

Immunogenic necroptosis in liver diseases: mechanisms and therapeutic potential.

Necroptosis has received increasing attention and is extensively studied as a recently discovered mode of cell death distinct from necrosis and apoptosis. It is a programmed cell death with a necrotic morphology that occurs in various biological processes, including inflammation, immune response, embryonic development, and metabolic abnormalities. Necroptosis is indispensable in maintaining tissue homeostasis in vivo and closely correlates with the occurrence and development of various diseases. First, we outlined the etiology of necroptosis and how it affects the onset and development of prevalent liver diseases in this review. Additionally, we reviewed the therapeutic strategy by targeting the necroptosis pathway in related liver diseases. We conclude that the necroptosis signaling pathway is critical in the physiological control of liver diseases' onset, progression, and prognosis. It will likely be used as a therapeutic target in the future. Further research is required to determine the mechanisms governing the necroptosis signaling pathway and the effector molecules.

Evaluation of in vivo antibacterial drug efficacy using Caenorhabditis elegans infected with carbapenem-resistant Klebsiella pneumoniae as a model host.

Objective: This study was developed to assess the in vivo antimicrobial activity of specific drugs using a model system consisting of Caenorhabditis elegans (C. elegans) infected with Carbapenem-resistant Klebsiella pneumoniae (CRKP) in an effort to identify promising drugs for CRKP-infected patient treatment. Methods: A C. elegans-CRKP liquid assay platform was developed and used to conduct limited in vivo screening for antimicrobial agents with potential activity against CRKP. Time curves for 10 different concentrations of tested antimicrobial agents were tested in this model system at 0, 2, 6, 8, and 12 h after treatment. The protective effects of these different antimicrobial agents were compared at different time points. Furthermore, ten CRKP strains samples were isolated from clinical specimens to demonstrate the applicability of the nematode model method, and two typical clinical cases are presented. Results: CRKP bacteria were sufficient to induce C. elegans death in a dose- and time-dependent fashion, while effective antimicrobial agents improved the survival of these nematodes in a dose-dependent manner. Notably, PB and TGC exhibited robust antibacterial protection within 12 h even at low tested concentrations, and clear efficacy remained evident for high doses of CAZ at this same time point as mediators of improved nematode survival. The results of C. elegans model method were well consistent with that using the Kirby-Bauer method in 10 CRKP strains samples, and two typical clinical cases showed applicability, reliability and efficacy of C. elegans model method. Conclusion: Overall, nematode models in drug sensitivity testing have shown advantages in clinical settings. Our results highlight the value of C. elegans model systems as tools for the simultaneous screening of different agents for in vivo antibacterial efficacy and are deserved further study.

Prediction of Prognosis in Adult Patients With Carbapenem-Resistant Klebsiella pneumoniae Infection.

OBJECTIVE: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are associated with poor patient outcomes. We aimed to analyze the clinical information of adult patients with CRKP infection in order to establish a nomogram for mortality risk as well as to determine the treatment effectiveness of different antimicrobial regimens. METHODS: Adult patients diagnosed with CRKP infection in a tertiary hospital in Shanghai between September 2019 and March 2021 were included. The clinical characteristics and clinical outcomes of these patients were analyzed. RESULTS: A total of 199 cases of CRKP infection were examined. Five factors, namely age ≥65 years, respiratory failure, Sequential Organ Failure Assessment score, serum procalcitonin ≥5 ng/mL, and appropriate treatments in 3 days, were found to be associated with 30-day mortality. Upon incorporating these factors, the nomogram achieved good concordance indexes of 0.85 (95% confidence interval [CI]: 0.80-0.90) and well-fitted calibration curves. Receiver-operating characteristic curves for 7-, 15-, and 30-day survival had areas under the curve of 0.90, 0.87, and 0.88, respectively. Three-drug combination therapy was observed to be associated with lower mortality in the high-risk group (adjusted hazard ratio = 0.24, 95% CI: 0.06-0.99) but not in the low-risk group. Ceftazidime-avibactam, fosfomycin, and amikacin were effective against infections caused by CRKP. Tigecycline improved the treatment efficiency in 7 days, but a trend toward increased mortality was seen (HR, 1.69; 95% CI: 0.98-2.94; P = 0.061). CONCLUSION: The antimicrobial regimen efficacy data and the predictive nomogram established in this study can help clinicians in identifying high-risk adult patients with CRKP infection, improving the therapeutic effect, and reducing mortality.

Engineering Macrophages for Cancer Immunotherapy and Drug Delivery.

Macrophages play an important role in cancer development and metastasis. Proinflammatory M1 macrophages can phagocytose tumor cells, while anti-inflammatory M2 macrophages such as tumor-associated macrophages (TAMs) promote tumor growth and invasion. Modulating the tumor immune microenvironment through engineering macrophages is efficacious in tumor therapy. M1 macrophages target cancerous cells and, therefore, can be used as drug carriers for tumor therapy. Herein, the strategies to engineer macrophages for cancer immunotherapy, such as inhibition of macrophage recruitment, depletion of TAMs, reprograming of TAMs, and blocking of the CD47-SIRPα pathway, are discussed. Further, the recent advances in drug delivery using M1 macrophages, macrophage-derived exosomes, and macrophage-membrane-coated nanoparticles are elaborated. Overall, there is still significant room for development in macrophage-mediated immune modulation and macrophage-mediated drug delivery, which will further enhance current tumor therapies against various malignant solid tumors, including drug-resistant tumors and metastatic tumors.

AIF1 was identified as an up-regulated gene contributing to CSFV Shimen infection in porcine alveolar macrophage 3D4/21 cells.

Classical swine fever (CSF) is a disease that is characterized by diffuse hemorrhaging, high fever, and high mortality rates. The pro-inflammatory characteristics of allograft inflammatory factor 1 (AIF1) have been well documented; however, insufficient attention has been given to porcine AIF1. In the present study, AIF1 was identified as a key player contributing to CSFV Shimen infection in porcine alveolar macrophage (PAM) 3D4/21 cell line. Our evaluation showed that AIF1 mRNA and protein are expressed at a time-dependent high level in CSFV Shimen-infected PAM 3D4/21 cells. The transcription and translation of IL6 were also significantly upregulated in infected PAM 3D4/21 cells. By utilizing overexpression RNAs approach, we showed that the cellular AIF1 induced an increased IL6 in PAM 3D4/21 cells. Furthermore, silencing of AIF1 suppressed CSFV Shimen-induced IL6 production in PAM 3D4/21 cells and also inhibited CSFV replication, whereas overexpression of recombinant AIF1 was beneficial for the replication of CSFV Shimen and promoting IL6 production in CSFV Shimen-infected PAM 3D4/21 cells. It is suggested CSFV Shimen induced IL6 in PAM 3D4/21 cells via AIF1 activation, which help clarify the AIF1-related inflammatory processes that occur on CSFV Shimen infected macrophages.

Pharmacokinetic studies of meloxicam following oral and transdermal administration in Beagle dogs.

AIM: The potential for topical delivery of meloxicam was investigated by examining its pharmacokinetic profiles in plasma and synovial fluid following oral and transdermal administration in Beagle dogs. METHODS: The experiment was a two-period, crossover design using 6 Beagle dogs. Meloxicam tablets were administered orally at a dose of 0.31 mg/kg, and meloxicam gel was administered transdermally at a dose of 1.25 mg/kg. Drug concentrations in plasma and synovial fluid were determined by liquid chromatography-tandem mass spectrometry (LC/MS/MS). The pharmacokinetic parameters were calculated using the Topfit 2.0 program. RESULTS: The pharmacokinetic results showed that AUC(0-t) (23.9+/-8.26 microg.h.mL(-1)) in plasma after oral administration was significantly higher than after transdermal delivery (1.00+/-0.43 microg.h.mL(-1)). In contrast, the ratio of the average concentration in synovial fluid to that in plasma following transdermal administration was higher than that for an oral delivery. The synovial fluid concentration in the treated leg was much higher than that in the untreated leg, whereas the synovial fluid concentration in the untreated leg was similar to the plasma concentration. CONCLUSION: The high concentration ratio of synovial fluid to plasma indicates direct penetration of meloxicam following topical administration to the target tissue. This finding is further supported by the differences observed in meloxicam concentrations in synovial fluid in the treated and untreated joints at the same time point. Our results suggest that transdermal delivery of meloxicam is a promising method for decreasing its adverse systemic effects.Acta Pharmacologica Sinica (2009) 30: 1060-1064; doi: 10.1038/aps.2009.73; published online 8 June 2009.

In vivo assessment of novel furosemide gastro-mucoadhesive delivery system based on a kind of anion ion-exchange fiber.

A novel gastro-mucoadhesive delivery system based on a kind of anion ion-exchange fiber has been developed. Furosemide (FM), which is site-specifically absorbed from the upper gastrointestinal (GI) tract, was used as model drug. A novel-modified dissolution system, which can also be called "flow through diffusion cell," was used to study the drug release from the drug fibers. The GI transit studies of the FM fiber complexes in rats and gamma imaging studies in volunteers were carried out to evaluate the gastro-mucoadhesive behavior of the fiber. The pharmacokinetic profile and parameters of the FM suspension and FM fiber in fasted and fed rats were measured, respectively. Studies on rats and volunteers provided evidence for the validity of the hypothesis that the drug fiber provided better gastro-mucoadhesive properties in vivo.

Mechanism of ultrasonic impregnation on porosity of activated carbons in non-cavitation and cavitation regimes.

Ultrasonic impregnation has proven to be an effective method to improve surface area and pore volume during preparation of activated carbons. However, the mechanism by which the promotion effect of ultrasonic impregnation is still ambiguous. Fundamental wave pressure (FWP) and broadband integrated pressure (BIP) were used to estimate the non-cavitation (vibration) energy and cavitation energy, respectively. The effects of FWP and BIP on the pore volume, surface area, surface functional groups, and microcosmic morphology were investigated in non-cavitation and cavitation regimes. Ultrasonic vibration promoted the surface enlargement and pore development of activated carbons, and it mainly affected the development of mesopore volume (Vmes) in both the pore volume and the mesopore-size-distribution range. The Vmes was enhanced by 60%-100% in the non-cavitation regime. Ultrasonic cavitation also facilitated porosity development of activated carbons, and it mainly affected the development of specific surface area (SBET) and micropore volume (Vmic). The excessive cavitation led to a decrease of the porosity of activated carbons, so the BIP should be optimized during impregnation. The highest SBET, Vmic, and Vmes for activated carbons were obtained by in the presence of both FWP and BIP, which were enhanced by 29.05%, 30.23%, and 113.33%, respectively, compared with the corresponding value for the activated carbon prepared without using ultrasonic impregnation. This work provided new insight into the role of the acoustic energy present during impregnation in tuning properties of activated carbons.

Cloud point extraction-HPLC method for determination and pharmacokinetic study of flurbiprofen in rat plasma after oral and transdermal administration.

A method based on cloud-point extraction (CPE) was developed for the determination of flurbiprofen (FP) in rat plasma after oral and transdermal administration by high-performance liquid chromatography coupled with UV detection (HPLC-UV). The non-ionic surfactant Genapol X-080 was chosen as the extract solvent. Variables parameter affecting the CPE efficiency were evaluated and optimized. Chromatography separation was performed on a Diamond C(18) column (4.6 mm i.d. x 250 mm, 10 microm particle size) by isocratic elution with UV detection at 254 nm. The assay was linear over the range of 0.2-50 and 0.1-10 microg/ml for oral and transdermal administration, respectively, and the lower limit of quantification (LLOQ) was 0.1 microg/ml. The extraction recoveries were more than 84.5%, the accuracies were within +/-3.8%, and the intra- and inter-day precisions were less than 10.1% in all cases. After strict validation, the method indicated good performance in terms of reproducibility, specificity, linearity, precision and accuracy, and it was successfully applied to the pharmacokinetic study of flurbiprofen in rats after oral and transdermal administration.