EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 4.384
Ling-Yang Wang,Fan-Zhi Bu,Yue-Ming Yu,Yuan-Yuan Niu,Yan-Tuan Li,Cui-Wei Yan,Zhi-Yong Wu
In order to exploit the advantages to the full of multidrug salification strategy in amending the pharmaceutical properties of drugs both in vitro and in vivo , and further to open up a new way for its applications in bacteria-virus mixed cross-infection drugs, a novel dual-drug crystalline molecular salt hybridizing antibacterial drug sulfamethoxazole (SFM) with antiviral ingredient amantadine (ATE), namely SFM-ATE, is successfully designed and synthesized via multidrug salification strategy oriented by proton exchange reaction. The crystal structure of the firstly obtained molecular salt is precisely identified by employing single-crystal X-ray diffraction and multiple other techniques. The results show that, in the crystal lattice of molecular salt SFM-ATE, the classical hydrogen bonds together with charge-assisted hydrogen bonds contribute to two- dimensional networks, between which the hydrophobic interaction plays an important role. The relevant in vitro/vivo pharmaceutical properties of the dual-drug molecular salt are carried out through a comparative investigation of theoretical and experimental methods. It has been found that SFM displays concurrent improvements over the bulk drug in its permeability and dissolution after forming the molecular salt, which is supported by the molecular electrostatic potential calculation and Hirshfeld surface analysis. Encouragingly, the perfected in vitro biopharmaceutical properties can effectually turn into the in vivo pharmacokinetic preponderances with the expedited peak plasma concentration, lengthened half-life and enhanced bioavailability. Better yet, the antibacterial activities of SFM from the molecular salt get stronger with enlargement in inhibition areas and reduction in values of minimum inhibitory concentrations against the tested bacterial strains. Consequently, the present contribution not only supplies an opportunity for widening applications for classical sulfa drugs via dual-drug salification strategy, but also offers an alternative approach in dealing with viral-bacterial coinfection even other complex diseases by drugs’ hybridization at the molecular level.
研究领域:
药学
·
生物化学
·
传染病学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2021
·
IF 6.53
Mariana Carolina Di Santo,Cecilia Luciana D’ Antoni,Ana Paula Domínguez Rubio,Agustina Alaimo,Oscar Edgardo Pérez
Plant-based polyphenols are natural compounds, present in fruits and vegetables. During recent years, polyphenols have gained special attention due to their nutraceutical and pharmacological activities for the prevention and treatment of human diseases. Nevertheless, their photosensitivity and low bioavailability, rapid metabolism and short biological half-life represent the major limitations for their use, which could be overcome by polyphenols encapsulation (flavonoids and non-flavonoids) into chitosan (CS)-tripolyphosphate (TPP) based nanoparticles (NP). In this review, we particularly focused on the ionic gelation method for the NP design. This contribution exhaustively discusses and compares results of scientific reports published in the last decade referring to ionic gelation applied for the protection, controlled and site-directed delivery of polyphenols. As a consequence, CS-TPP NP would constitute true platforms to transport polyphenols, or a combination of them, to be used for the designing of a new generation of drugs or nutraceuticals.
研究领域:
药剂学
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生物技术
·
纳米技术
·
食品科学
·
药理学
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DOI
PubMed
高影响因子
JOURNAL OF ALLOYS AND COMPOUNDS
·
2023
·
IF 6.2
Weiqiang Li,Qixiu You,Jingjing Zhang,Wen Li,Hengyi Xu
Green synthesis of antibacterial metal oxide nanoparticles is attractive for develop novel antibacterial agents. In this study, probiotic strain Lactobacillus plantarum ZDY2013 fermentation liquid (LFL) was utilized for the synthesis of zinc oxide nanoparticles (called as LFL-ZnO) via an ultrasound-microwave-facilitated procedure. SEM and TEM show the synthesized LFL-ZnO with a spherical morphology that are surrounded by LFL. Zeta potential and hydrodynamic sizes were − 25.533 ± 0.205 mV and 537.5 nm by dynamic light scattering (DLS) analyzer, respectively. X-ray diffraction (XRD) results revealed the hexagonal wurtzite structure of LFL-ZnO with a crystallite size of 41 nm. Fourier transform infrared (FTIR) spectrum and thermal gravimetric (TG) curve showed the structure differences between H-ZnO (synthesized by ddH 2 O instead of LFL) and LFL-ZnO. In addition, LFL-ZnO significantly inhibited the growth of methicillin-resistant Staphylococcus aureus (MRSA) with MIC = 100 μg/mL. The possible antibacterial mechanisms may be attributed to LFL-ZnO release a high concentration of Zn 2+ inducing the destruction of bacterial cell integrity resulting in the leakage of protein and reducing sugars. Meanwhile, CLSM results demonstrate the generation of reactive oxygen species (ROS) by LFL-ZnO is another important antibacterial mechanism. The synthesized LFL-ZnO has broad potential to be developed in pharmaceutics as an effective antimicrobial nanomaterial .
研究领域:
纳米技术
·
微生物学
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材料科学
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药学
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产品关联
DOI
高影响因子
Carbohydrate Polymer Technologies and Applications
·
2025
·
IF 6.5
Yao Fu,Shuwen Tan,Xiaojia Xu,Wenlong Xing,Qi He,Yi Lu,Jia Tang,Xiaoyan Liu,Yu Fang
Natural polysaccharides are widely used in biomedical and pharmaceutical applications due to their biocompatibility and biodegradability. In this study, alginate-based Poly( N -vinylcaprolactam)- co -sodium alginate (P(VCL- co -SA)) microgel particles with different mass ratios of VCL/SA were synthesized and employed as stabilizers for curcumin-loaded Pickering emulsions. The obtained P(VCL- co -SA) microgels display a uniform, spherical morphology with low polydispersity. Moreover, the microgels demonstrated high interfacial activity at the dodecane/water interface, enabling the stabilization of dodecane-in-water emulsions across a broad pH range (3–9) at 25°C. At an elevated temperature (55°C), the emulsions remained stable at pH 6 and 9 (above the p K a of alginate, ∼3.5), while phase separation was observed at pH 3 below the p K a . The emulsion stability was further enhanced by optimizing Ca 2+ ion concentration. Furthermore, high internal phase soybean oil-in-water emulsions stabilized by P(VCL 83 - co -SA 17 ) microgels were successfully developed for curcumin encapsulation. The emulsions provided excellent protection for curcumin at room temperature. When incubated at 37°C, curcumin retention was significantly enhanced after the addition of Ca 2+ ions. Compared to previously reported systems that encapsulate curcumin in emulsions, the present approach exhibits superior performance, such as, encapsulation efficiency and retention rate. These findings provide insights into the development of high-performance Pickering emulsions that are stabilized by natural products and highlight their potential applications in food technology and the pharmaceutical industry.
研究领域:
食品科学与技术
·
药学
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胶体与界面化学
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高分子材料
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药物递送系统
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产品关联
DOI
高影响因子
CRYSTAL GROWTH & DESIGN
·
2025
·
IF 3.4
Ling Chen,Xiao-Qin Ma,Hai-Li Wu,Shun Zhang,Jie-Feng Chen,Ning Lin,Qing Chen
Glioblastoma is a highly aggressive brain tumor with a poor prognosis and limited treatment options. Resveratrol (RES) and temozolomide (TMZ) both showed significant antitumor activity in GBM therapy. However, they are limited by poor solubility and stability, respectively. This study reports the first successful development of a resveratrol–temozolomide (RES–TMZ) cocrystal. The cocrystal significantly improved the solubility of RES and stability of TMZ, while it exhibited enhanced oral bioavailability in rats. In vitro cytotoxicity assays revealed that the RES–TMZ cocrystal showed superior inhibitory effects on U87 glioma cell proliferation and induced a higher apoptosis rate compared to that of monotherapy or physical mixtures. Mechanistic studies further demonstrated that the cocrystal exerts its effects through the mitochondrial-dependent apoptotic pathway, characterized by the upregulation of the proapoptotic protein Bax, downregulation of the antiapoptotic protein Bcl-2, activation of the caspase-3 pathway, and collapse of mitochondrial membrane potential coupled with a burst of intracellular reactive oxygen species. This work establishes pharmaceutical cocrystallization as a viable strategy to develop improved combination therapies for glioblastoma by overcoming drug limitations while potentiating therapeutic effects.
研究领域:
药学
·
肿瘤学
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药物递送
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晶体工程
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凋亡研究
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产品关联
DOI
高影响因子
Acta Pharmaceutica Sinica B
·
2025
·
IF 14.6
Haiyan Wang,Zhichao Sun,Chunlei Dai,Ran Liao,Ran Lin,Liying Wang,Wenjun Fu,Ruhe Zhang,Danwen Zheng,Zhongde Zhang,Jun Wu,Yuntao Liu
Acute respiratory distress syndrome (ARDS) is a life-threatening disease. In the clinical management of ARDS, current treatments such as glucocorticoids and protease inhibitors encounter significant challenges due to their high toxicity, limited administration routes, or poor targeting. These limitations highlight the urgent need for innovative therapeutic strategies. Songorine (Son), a compound derived from the herb Aconitum carmichaelii Debeaux, possesses good antioxidant and anti-inflammatory properties, exhibiting great potential for treating ARDS. However, its clinical application is partially constrained by low aqueous solubility and uncertain efficacy for ARDS. In this study, we developed a lung-targeted lipid nanomedicine by encapsulating Son in dipalmitoyl phosphatidylcholine (DPPC) liposomes (Son@liposome, Son-lipo). In a lipopolysaccharide-induced ARDS mouse model, we demonstrated that Son-lipo effectively targeted inflamed lung tissues with commendable biocompatibility. Further, Son-lipo significantly alleviated multiple ARDS phenotypes such as endothelial barrier damage, lung edema, pulmonary dysfunction, and alveolar lesion, which involved uncontrolled inflammation, oxidative stress, and cell apoptosis. RNA sequencing and Western blotting analyses revealed that Son-lipo inhibited the activation of the TLR4/NF- κ B/NLRP3 pathway responsible for ARDS. In conclusion, our study successfully developed an inhalable lipid-nanomedicine (Son-lipo) as a novel therapeutic strategy for ARDS. It elucidates the compound's ability to mitigate ARDS by repairing the endothelial barrier and reversing the inflammatory microenvironment, thereby providing a promising candidate drug for improving clinical management of ARDS.
研究领域:
纳米医学
·
呼吸系统疾病
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药学
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炎症研究
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药物递送
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2025
·
IF 4.7
Yusong Zhang,Wei Shi,Huanlin Li,Lei Yang,Lei Hou,Cheng Ma
Enantiomers often exhibit significant differences or even diametrically opposed effects in pharmacological activity, toxicological properties, and metabolic behavior. Single-enantiomer drugs frequently demonstrate distinct advantages over the racemate. Therefore, accurately distinguishing between enantiomers and racemate is particularly crucial in the fields of chemistry and biomedicine. Racemates, as mixtures of equal amounts of the enantiomers (levorotating and dextrorotating), exist in two forms: racemic mixtures and racemic compounds. Racemic compounds exhibit differences from their enantiomers in absorption spectra, whereas racemic mixtures do not. This study investigates the absorption spectra of ( S )-(+)-2-phenylpropionic acid, ( R )-(-)-2-phenylpropionic acid, and their racemates using terahertz time-domain spectroscopy technology. Experimental results indicate that the enantiomer exhibits absorption peaks similar to those of the racemic mixture, but with a significant difference in absorption intensity. Further combined with density functional theory (DFT), theoretical spectral calculations were performed on the solid state and solution enantiomers based on single molecule and unit cell models respectively. It was found that the enantiomeric simulation spectra were highly consistent. After the sample transitioned from solid to solution state, changes in hydrogen bonds would change its molecular vibration characteristics and intermolecular interaction patterns.
研究领域:
物理化学
·
光谱学
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手性化学
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药学
·
计算化学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Man Zhang,Yuanpeng Wang
Transdermal insulin delivery using microneedle (MN) systems provides a promising, patient-friendly alternative to conventional subcutaneous injections. In this study, we developed a citric acid crosslinked carboxymethyl cellulose hydrogel microneedle (CMC-CA HMN) system capable of efficient insulin loading and rapid, pH-triggered release. Thermal esterification produced a CMC-CA hydrogel enriched with abundant carboxyl groups, facilitating electrostatic insulin loading under acidic conditions and immediate release at physiological pH. Fourier transform infrared (FTIR) spectroscopy confirmed successful ester crosslinking. The optimized hydrogel exhibited a high insulin loading capacity (8.7 mg g −1 ) driven primarily by electrostatic interactions. Mechanical tests demonstrated sufficient needle strength for reliable skin penetration, and ex vivo tests on porcine skin verified effective insertion and rapid insulin diffusion into dermal layers. In diabetic rats, a 0.6 IU insulin‑loaded HMN patch yielded glucose‑lowering and pharmacokinetic profiles closely matching those of a 0.2 IU subcutaneous injection, while 0.3 IU produced a smaller effect. Histological analyses further confirmed excellent biocompatibility. The developed CMC-CA HMN platform thus represents a scalable, safe, and efficient strategy for transdermal insulin delivery, substantially advancing the clinical potential of microneedle-mediated protein therapies.
研究领域:
药学
·
药物递送
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生物材料
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纳米医学
·
糖尿病研究
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产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2025
·
IF 5.4
Yu Sun,Li Cui,Wanqiu Peng,Rong Chen,Xueneng Guan,Jiangyun Liu
Parkinson’s disease (PD) is difficult to treat clinically and lacks an effective treatment. The aim of this study was to synthesize and characterize butyrate-modified hyaluronic acid (HA-But), validate its therapeutic efficacy, and elucidate its mechanisms of action in PD. Behavioral tests, including the open field test, Y-maze, and elevated plus maze test, demonstrated that HA-But significantly alleviated motor dysfunction in PD mice. ELISA results indicated a marked reduction in pro-inflammatory cytokine levels following the HA-But treatment. In addition, immunohistochemistry, immunofluorescence, and Western blot analyses revealed that HA-But improved dopaminergic neuron survival and reduced α-synuclein aggregation. Furthermore, HA-But activated PINK1/Parkin-mediated mitophagy, modulated gut microbiota composition, and increased short-chain fatty acid (SCFA) levels, especially butyric acid. Combining HA-But with gastrodin further improved the PD symptoms in mice. These findings suggested the potential of HA-But as a novel approach for PD treatment.
研究领域:
神经科学
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药学
·
分子生物学
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肠脑轴
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神经退行性疾病
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产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2025
·
IF 8.1
Yang Wang,Yanan Fu,Meiying Wu,Haoqiang Wan,Xinchun Chen,Lanlan Ge,Chenyan Shi,Yangfan Li,Xiaobin Zeng,Tianqi Wang
The chemotherapeutic drug doxorubicin (DOX) has been demonstrated to trigger pyroptosis in tumor cells at exceptionally high concentrations. Nevertheless, the administration of DOX at suprapharmacological doses could cause acute off-target cytotoxicity and severe adverse effects. Herein, a biflavonoid derivative, F24, was found to improve the sensitivity of hepatocellular carcinoma (HCC) cells to low-dose DOX and reduce the adverse effects of DOX. We demonstrated that F24 synergized with low-dose DOX to increase pyroptosis and autophagy in HCC cells through dual-target CDK6 inhibition/p53 activation at a proper ratio. To achieve this synergistic effect, nanodiscs with large hydrophobic cavities were selected to codeliver the low-dose hydrophobic drugs DOX and F24 (DOX-F24@Nanodisc, DF@N), which improved the tumor accumulation of the two drugs and ensured precise drug ratio integrity within the tumor cells. DF@N can trigger gasdermin-E (GSDME)-based pyroptosis in tumor cells, accompanied by the cleavage of caspase-3. Strikingly, knocking out GSDME or caspase-3 redirected DF@N-driven cellular death from the pyroptosis pathway to the apoptotic pathway. Furthermore, DF@N administration suppressed tumor growth and activated pyroptosis in a Huh7 mouse xenograft tumor model. Overall, F24 was found to induce autophagy by targeting CDK6 and had a synergistic effect on DOX-induced pyroptosis. These results indicate that the pyroptosis-induced DF@N nanodisc system provides an effective and secure therapeutic strategy for treating HCC.
研究领域:
肿瘤学
·
药学
·
分子生物学
·
纳米医学
·
癌症治疗
·
细胞死亡机制
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD SCIENCE
·
2025
·Vol. 90
·期 12
·e70725
·
IF 3.4
Jing Jing,Huizhen Li,Cheng Li,Mengjie Xu,Yana Zhao,Jianlan Cui,Zhijun Zhang
The leaves of Hemerocallis citrina Baroni ( H. citrina Baroni) are a promising source of bioactive polysaccharides (HCLP). However, the presence of abundant pigments in crude HCLP complicates subsequent purification and analysis, making an effective decolorization step essential. A model of decolorization conditions of HCLP was established using single factor and response surface methodology (RSM), and the optimal decolorization conditions were obtained. Subsequently, the HCLP-0.1 was successfully isolated via DEAE-52 cellulose column. Structural characterization revealed that HCLP-0.1 has a molecular weight ( M w ) of 8317.64 Da, composed of Man, GlcN, Rha, GlcA, GalA, Glc, Gal, Xyl, and Ara. Furthermore, HCLP-0.1 was characterized by α- and β-pyranose configurations, crystallinity, and an irregular triple-helical structure. Thermal analysis demonstrated excellent thermal stability. Antioxidant assays revealed that HCLP-0.1 possesses significant concentration-dependent (0.1–2.0 mg/mL) scavenging capacity against ABTS, hydroxyl, and DPPH radicals. These results support the potential of HCLP as a natural antioxidant, providing a solid basis for its future application in functional foods or pharmaceuticals.
研究领域:
生物化学
·
天然产物化学
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食品科学与技术
·
药学
·
多糖研究
·
抗氧化研究
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Shiting Xu,Wenhao Gao,Shuang Lin,Bingkun Kang,Xiaoting Shi,Da Zheng,Longyun Xiao,Lingjun Zeng,Qian Zhang,Wenjun Tian,Hongtao Song
Ferroptosis, a newly recognized mode of regulated cell death characterized by iron-mediated accumulation of lipid peroxides, represents a viable treatment strategy for metastatic colorectal cancer (CRC). Nonetheless, the clinical effectiveness of single-agent ferroptosis inducers is constrained by the adaptive and self-repair capabilities of tumor cells. To address this limitation, this study proposes a self-amplifying ferroptosis nanodrug SOR/QUE@HSA, which is engineered by coencapsulating sorafenib (SOR) and quercetin (QUE) within human serum albumin (HSA). SOR/QUE@HSA offers a uniform structure, improved stability, and enhanced drug delivery efficiency. The released SOR and QUE impeded the uptake of glutamine (Gln) and cysteine (Cys) by targeting solute carrier family 7 member 11 (SLC7A11) and solute carrier family 1 member 5 (SLC1A5), respectively. This dual inhibition consequently disrupts the synthesis of glutathione (GSH), resulting in a marked downregulation of glutathione peroxidase 4 (GPX4), ultimately enhancing ferroptosis in CRC. Additionally, QUE inhibits hexokinase-II (HK-II), which results in decreased ATP production and lactate (LA) generation, thereby impeding tumor metastasis. In summary, our findings unveil a plausible role for the therapeutic potential of QUE as a ferroptosis-inducing anticancer agent, and the synergistic combination of QUE and SOR within this nanoplatform presents an option for treating metastatic CRC.
研究领域:
肿瘤学
·
纳米医学
·
分子生物学
·
药学
·
细胞死亡研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）