JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2024
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IF 4.5
MengYing Lei,Qing Chen,Yang Wang,Gang Wang
Oral absorption of carrier-free self-assembly nanoplatform was limited by mucus barrier, p-gp efflux and liver metabolism. In this study, Pip-Cur-TA nanoparticle were constructed by co-assembly of tannic acid, curcumin and piperine via inter-molecular hydrogen-bonded and π-π interaction to improve the oral chemotherapy. The optimized Pip-Cur-TA nanoparticle showed an average diameter of 60 nm with a drug encapsulation efficiency of 67.02 % and loading capacity of 61.37 %. Pip-Cur-TA nanoparticles showed pH-dependent drug release, mucosal adhesion, inhibition of p-gp and liver metabolism and improved membrane permeability. Oral Pip-Cur-TA nanoparticle produced high oral delivery efficiency and relative oral bioavailability of 12.84 % in rats, and further showed significant tumor inhibition on PC-3 tumor cells. These findings confirmed that Pip-Cur-TA nanoparticle might be a promising oral drug formulation for chemotherapy.
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Frontiers in Pharmacology
·
2024
·
IF 4.4
Xin Qiao,Xiaojuan Cao,Shuang Xu,Cunlin Wang,Rui Guo,Xiaojuan Yao,Qiong Zhang
Background: Dysregulated and excessive inflammatory reactions can lead to tissue damage, which is the underlying cause of most human diseases. Menisoxoisoaporphine A (MA), a novel oxoisoaporphine alkaloid, was obtained from Menispermi Rhizoma, a traditional Chinese medicinal herb used in the treatment of inflammatory conditions in clinical practice. This suggests that MA has very promising potential for the development of anti-inflammatory therapeutics. Hence, this study aims to investigate the anti-inflammatory effects and underlying mechanisms of MA.Method: The anti-inflammatory effects of MA were evaluated in lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7 cells. Its underlying mechanisms were explored through RNA sequencing and Western blotting. The binding modes and interactions sites between MA and phosphodiesterase 4B (PDE4B) were predicted using molecular docking and validated by molecular dynamics simulation.Results: MA treatment significantly reduced LPS-induced morphological changes, inflammatory cytokine relesae, and proinflammatory genes expression in RAW264.7 cells compared to the LPS-induced controls. Transcriptome sequencing analysis suggested that PDE4B might be a key target for MA to exert its therapeutic effect. Mechanismly, MA directly acted on Tyr405 site of PDE4B, thus leading to a sustained elevation of the cyclic adenosine monophosphate (cAMP) levels, which subsequently inactivated NF-κB signaling pathway by phosphorylating protein kinase A (PKA). MA inhibited the NF-κB-mediated inflammatory response depending on PDE4B.Conclusion: MA, a natural and novel compound, exerted anti-inflammatory effects in LPS-induced RAW264.7 macrophage cells. It demonstrated a strong binding ability to the Tyr405 sites of PDE4B, thereby inhibiting NF-κB signaling pathway by regulating the cAMP-PKA axis. Elucidating the interaction between MA and PDE4B holds significant potential for the advancement of innovative therapeutic strategies aimed at inflammatory diseases. By strategically modulating this interaction, it may be feasible to achieve more precise regulation of inflammatory responses, thereby offering promising therapeutic benefits for conditions such as rheumatoid arthritis, asthma, and inflammatory bowel disease.
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BIOMACROMOLECULES
·
2024
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IF 5.5
Xiangyi Liu,Lulu Du,Jia Liu,Yueting Shi,Qipeng Liu,Ying Xu,Yingying Xia,Xiaiting Wang,Dan Ding,Xingyi Li,Deqing Lin
With the advantages of less invasiveness and better shape adaptability, in situ-forming hydrogels are desired biomaterials as scaffolds, drug carriers, and so on. Herein, a negatively charged NaCl-responsive ultrashort peptide sequence (EEH) is reported whose electrostatic repulsion can be reduced through the charge-shielding effect. Under physiological conditions, its AIEgen-capped amphiphile TPE-GEEH of low concentration (1 mg/mL) presents NaCl-triggered morphological transformation from micelle to closely packed fiber with enhanced emission, which can be applied to biosense sodium ion (Na+) with high sensitivity and quick response. At a slightly acidic pH, 10 mg/mL TPE-GEEH undergoes sol–gel transition upon addition of NaCl (100 mM) with improved mechanical properties, which should be useful to develop an in situ-forming hydrogel. Overall, our report provides a simple strategy to construct NaCl-responsive assemblies for potential application in biosensors and drug delivery system.
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TALANTA
·
2018
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IF 4.244
Chaonan Huang,Yun Li,Jiajia Yang,Junyu Peng,Jun Tan,Yun Fan,Longxing Wang,Jiping Chen
This paper describes the poly(divinylbenzene) (PDVB) supported synthesis of quaternized hyperbranched macromolecules (QHMs) and its use as a highly selective, high-capacity mixed-mode anion-exchange (MAX) sorbent . In detail, the aminated PDVB support was firstly synthesized by copolymerization of divinylbenzene and 2-(diethylamino)ethyl methacrylate via Pickering emulsion polymerization . The QHMs were then grafted on PDVB by a divergent synthesis involving consecutive reactions of resorcinol diglycidyl ether with methylamine (N, N-dimethylethanolamine for terminal epoxides), which brought in a high density of quaternary ammonium functionalities. The changes of specific surface area (S BET ), pore volume and ion exchange capacity (IEC) with generation number reveal that the QHMs have been grown successfully within the large meso-channels of the porous aminated PDVB. The best compromise between the S BET , pore volume and IEC was obtained at the 4th generation (G4). Due to the highest IEC (0.47 meq/g), the G4-QHMs was successfully applied for mixed-mode solid phase extraction (SPE) of acidic non-steroidal anti-inflammatory drugs (NSAIDs). An efficient approach based on the mixed-mode SPE coupled with HPLC-UV was developed for highly selective extraction and cleanup of nine NSAIDs (tolmetin, TLM; ketoprofen , KEP; naproxen , NAP; flurbiprofen , FLB; diclofenac, DIC; indomethacin, INM; ibuprofen , IBP; mefenamic acid , MFA; tolfenamic acid , TFA) in human urine samples. Under the optimized conditions, the method exhibited satisfactory recoveries ranging from 81.9% to 104.0% with relative standard deviation (RSD) values below 8.5%, good sensitivity (0.004–0.009 μg mL −1 limit of detection) and good linearity (coefficient of determination, R 2 > 0.997, 0.01–0.2 μg mL −1 for NAP, 0.05–1.0 μg mL −1 for FLB, DIC, INM, MFA, TFA, 0.1–2.0 μg mL −1 for TLM, KEP, IBP). The hyperbranched MAX sorbent is superior to Oasis HLB and comparable to Oasis MAX in obtaining clean chromatographic profiles. Our results demonstrate the potential application of the hyperbranched MAX for complex sample analysis.
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ANALYTICA CHIMICA ACTA
·
2020
·
IF 5.977
Xiaofei Han,Jia Chen,Zhan Li,Kaijun Quan,Hongdeng Qiu
A magnetic porous carbon (Fe 3 O 4 @PC) was successfully fabricated based on combustion combined with solvothermal method , and then used as magnetic solid-phase extraction absorbent for the determination of four triazole fungicides . The porous carbon was fabricated by imperfect combustion of filter paper loaded with zinc nitrate hexahydrate, which possessed extremely abundant pores, high specific surface area (908.05 m 2 g −1 ) and large pore volume . Due to the introduction of solvothermal method used to prepare Fe 3 O 4 @PC, homogeneously distributed magnetic nanoparticles and high saturation magnetization were obtained. Compared with another magnetic porous carbon (Fe 3 O 4 @C), Fe 3 O 4 @PC obviously enhanced enrichment factors and extraction recoveries. Several key parameters influencing extraction efficiency were optimized. The satisfactory enrichment factors, low limits of detection of the method and good linearities were achieved under the optimal conditions. The relative recoveries ranged from 82.8% to 113.2% in three spiked real samples with relative standard deviations lower than 6.2%. The results indicated the great potential of the novel Fe 3 O 4 @PC as adsorbent for the extraction of triazole fungicides from complex real samples.
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CHEMISTRY & BIODIVERSITY
·
2024
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IF 2.3
Shu-Hang Li,Meng-Ying Li,Tao-Tao Yuan,Guo-Wei Wang,Jian-Bin Zeng,Zhimian Shi,Jian-Hang Liu,Jun-Cheng Su
Osthole (also known as Osthol) is the main anti-inflammatory coumarin found in Cnidium monnieri and severs as the exclusive quality-controlled component according the Chinese Pharmacopoeia. However, its underlying anti-inflammatory mechanism remains unknown. In this study, we demonstrated that Osthole treatment significantly inhibited the generation of TNF-α, but not IL-6 in the classical LPS-stimulated RAW264.7 macrophage model. In addition, LPS induced the activation of both MAPK and NF-κB signalling pathways, of which the former was dose-dependently restrained by Osthole via suppressing the phosphorylation of JNK and P38 proteins, while the phosphorylation of IκB and P65 proteins remained unaffected. Interestingly, Osthole dose-dependently up-regulated the expression of the key cholinergic anti-inflammatory pathway regulator α7nAChR, and the TNF-α inhibition effect of Osthole was also significantly alleviated by the treatment of α7nAChR antagonist methylbetaine. These results demonstrate that Osthole may regulate TNF-α by promoting the expression of α7nAChR, thereby activate the vagus nerve-dependent cholinergic anti-inflammatory pathway.
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2025
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IF 5.4
Yang Yu,Lixin Fan,Chunling Gao,Yang Ping,Liting Mu,Weitong Sun
Despite the advances made in cancer treatment, malignant tumors remain a significant threat to human health. Tumor multidrug resistance (MDR) constitutes a significant impediment to the effectiveness of chemotherapy. Thus, the reversal of MDR has become a critical research domain for medical professionals. Now, paclitaxel (PTX) is encapsulated in a reduction-sensitive polymer pre-drug micelle called mPEG-SS-IND(PSI), which reduces the MDR of PTX and enhances its anti-tumor efficacy. The PSI/PTX micelles show excellent reduction sensitivity and stability. In vitro , the harmful effect of PTX on MCF-7/PTX cells is enhanced by the PSI/PTX micelles, while its damaging effect on normal cells is decreased. Furthermore, compared to PTX solution, PTX encapsulated in PSI/PTX micelles exhibits reduced volume distribution and clearance, longer blood circulation time, and greater drug concentration area under the curve. Furthermore, in vivo studies using BALB/c subcutaneous tumor-bearing mice demonstrate decreased systemic toxicity and enhanced therapeutic effectiveness of PTX. This study proves that the potential utility of reduction-sensitive polymer pre-drug micelles as a delivery method for overcoming MDR for PTX and targeting tumors.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Yadan Zhang,Xiaoyu Zhang,Tianhan Kai,Lin Zhang,Anping Li
Plant-derived exosome-like nanovesicles (ELNs) are nano-sized vesicles extracted from edible plants. Lycium ruthenicum Murray (LRM) has been gaining increasing attention due to its nutritional and medicinal value, but the ELNs in LRM has not been reported. In this study, LRM-ELNs were obtained, and the proteins, lipids, microRNAs (miRNAs) and active components in LRM tissues and LRM-ELNs was analyzed by LC-MS/MS, LC-MS, high-throughput sequencing techniques, and physical and chemical analysis. LRM-ELNs can be uptaken by PC12 cells through macropinocytosis and caveolin-mediated endocytosis primarily. Transcriptomic and western blot experiments indicate that LRM-ELNs can inhibit Aβ-induced apoptosis in PC12 cells through the MAPK and PI3K/AKT signaling pathways, with miRNAs playing a crucial role. These results indicate that LRM-ELNs have the protection effect on PC12 cells and can be considered as dietary supplements for alleviating neurodegenerative diseases.
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ACS Sensors
·
2025
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IF 9.1
Lian Xu,Yan Xiao,Kun Yu,Hongshuo Pan,Jiayi Xu,Yiyun Guan,Mengke Wang,Xiangyu Xu,Hao Wang
The improper application of nonsteroidal anti-inflammatory drugs (NSAIDs) presents significant health hazards via vector food contamination. A critical limitation of these traditional existing approaches is their inability to concurrently discern and distinguish among diverse NSAIDs, presenting a notable gap in the analytical capabilities within this domain. Herein, a creative dual-channel fluorescence sensor array was developed for the rapid discrimination and determination of NSAIDs, utilizing complexes of cucurbit[8]uril (CB[8]) with three distinct modified poly(ethylenimines) (PEIs) to address this challenge. The array successfully differentiated and identified 19 NSAIDs with 97% accuracy at a concentration of 1 mM. In addition, it also achieved analyses of individual NSAIDs across a range of concentrations, NSAID mixtures, and impurities of aspirin using statistical analysis methods. More importantly, the approach effectively detected NSAIDs in complex matrices, such as milk and urine, demonstrating its potential for real-world applications.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
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IF 4.8
Li Guo,Sai Zhang,Cong Zhang,Shuang Ren,Zihan Zhou,Fengyuan Wang,Yuexuan Wang,Qiqi Chen,Yubing Wang,Wen-Hui Lee,Kui Zhu,Di Qin,Yuanyuan Gao,Tongyi Sun
Inflammatory pain is a chronic pain caused by peripheral tissue inflammation, seriously impacting the patient’s life quality. Cinobufacini injection, as a traditional Chinese medicine injection preparation, shows excellent efficacy in anti-inflammatory and analgesic treatment in patients with advanced tumors. In this study, a novel analgesic peptide CI5 with anti-inflammatory and analgesic bio-functions that naturally presents in Cinobufacini injection and its regulatory mechanism are reported. Our results showed that the administration of CI5 significantly relieved the pain of mice in the acetic acid twisting analgesic model and formalin inflammatory pain model. Furthermore, CI5 effectively reduced the inflammatory cytokines (IL-6, TNF-α and IL-1β) and inflammatory mediator (PGE2) expressions, and prevented the carrageenan-induced paw edema in mice. Further LC-MS/MS results showed the anti-inflammatory and analgesic bio-functions of CI5 depended on its interaction with the Rac-2 protein upstream of ERK1/2 and the inflammatory signaling pathway (ERK1/2/COX-2 axis). In summary, CI5, as a novel natural candidate identified from Cinobufacini injection, showed substantial clinical promise for inflammatory pain treatments.
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BIOMACROMOLECULES
·
2024
·
IF 5.5
Yuhan Yang,Yangyi Chen,Yue Wei,Wei Wu,Qing Wang,Tianyun Xue,Xiaoyan Zhang,Wei Chen,Wei Zhang
A drug delivery system based on silybin-conjugated chitosan (CS-SB) polymeric micelles was developed to improve the oral absorption of doxorubicin (DOX). SB was grafted to CS via succinic acid, and CS-SB was identified by 1H NMR and FT-IR. The DOX-loaded micelles were prepared by self-assembly, and the characteristics of micelles, including a small particle size of 167.8 ± 2.3 nm, a high drug loading capacity of 8.59%, and a low critical micelle concentration of 1.3 × 10–5 g/mL, were demonstrated. The micelles showed oral bioavailability of up to 193% versus DOX·HCl. The cytotoxicity test showed the biosafety of CS-SB and the potential of reductive DOX-induced cardiotoxicity. The inhibition of P-gp efflux and CYP3A4 enzyme in CS-SB micelles was confirmed by cellular uptake and enzyme activity inhibition tests. The endocytosis process of micelles was revealed by an endocytosis inhibition test. The findings exhibited the potential of CS-SB micelles in drug delivery.
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JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-19
·
IF 10.6
Tang Bo,Wang Qiuxiang,Zhang Guowei,Zhang Aiwen,Zhu Lu,Zhao Rongrong,Gu Hongwei,Meng Jie,Zhang Junfang,Fang Guihua
Traditional eye drops are administered via topical instillation. However, frequent dosing is needed due to their relatively rapid precorneal removal and low ocular bioavailability. To address these issues, stearoyl L- carnitine-modified nanoemulsions (SC-NEs) were fabricated. The physicochemical properties of SC-NEs in terms of size, morphology, zeta potential, encapsulation efficiency, and in vitro drug release behavior were characterized. The cellular uptake and mechanisms of SC-NEs were comprehensively studied in human corneal epithelial cells and the stearoyl L- carnitine ratio in SC-NEs was optimized. The optimized SC-NEs could target the novel organic cation/carnitine transporter 2 (OCTN2) and amino acid transporter B (0 +) (ATB 0,+ ) on the corneal epithelium, which led to superior corneal permeation, ocular surface retention ability, ocular bioavailability. Furthermore, SC-NEs showed excellent in vivo anti-inflammatory efficacy in a rabbit model of endotoxin-induced uveitis. The ocular safety test indicated that the SC-NEs were biocompatible. In general, the current study demonstrated that OCTN2 and ATB 0,+ -targeted nanoemulsions were promising ophthalmologic drug delivery systems that can improve ocular drug bioavailability and boost the therapeutic effects of drugs for eye diseases. Graphical Abstract
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危险品化学品经营许可证（带存储）