Current treatments for ulcerative colitis (UC) often fail to adequately address its multifactorial pathogenesis, involving oxidative stress, barrier dysfunction, and gut microbiota dysbiosis. This study evaluated the therapeutic potential and multi-targeting mechanism of a ginseng, salvia root, and notoginseng oral solution (GSNS) in a DSS-induced mouse colitis model. Based on HPLC-MS/MS technology, 24 major bioactive components were identified. Following the induction of UC with 3.5% dextran sulfate sodium (DSS) in C57BL/6J mice, the animals were treated with GSNS (40, 80, or 160 mg/kg/day) or 5-Amino Salicylic Acid (5-ASA). The therapeutic efficacy was assessed via disease activity, histopathological staining, cytokines, and oxidative stress analysis, and barrier integrity test. Combined data from Western blot, qPCR, immunohistochemistry, electron microscopy, and 16S rRNA sequencing indicate that the therapeutic effect of GSNS against colitis is attributable to its dual role in dampening pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and potentiating antioxidant defenses via the Nrf2/HO-1 signaling pathway. It also upregulated Occludin expression, repaired tight junctions, and beneficially reshaped the gut microbiota by increasing Prevotellaceae and suppressing Escherichia-Shigella. These findings demonstrated that GSNS exerts a multi-target effect against colitis by synergistically enhancing antioxidant defense, repairing the intestinal barrier, and modulating microbial ecology, supporting its potential as a promising natural compound-based candidate for UC treatment.

Ulcerative colitis (UC) is an inflammatory bowel disease associated with oxidative stress. Pogostemon oil (PO) exhibits potent antioxidant and anti-inflammatory activities but is limited by high volatility and poor gastrointestinal stability. In this study, sporopollenin exine capsules (SECs) were engineered as natural micro-carriers for PO, achieving efficient encapsulation (η > 69%) and a high adsorption capacity (27.64 g/g). A pH-sensitive calcium alginate shell was subsequently applied to construct colon-targeted microspheres (Ca-Alg@PO-SECs). The resulting system improved the thermal and photostability of PO. In vitro dissolution assays confirmed the system's pH-responsiveness, maintaining integrity under simulated gastric conditions while enabling localized release at intestinal pH. In a DSS-induced acute UC mouse model, Ca-Alg@PO-SECs effectively alleviated clinical symptoms, as evidenced by improved body weight, colon length, and disease activity index. At the inflammatory level, the formulation modulated key cytokines (IL-1β, IL-6, and IL-10). Overall, Ca-Alg@PO-SECs provides a biocompatible, colon-targeted delivery strategy that preserves the bioactivity of essential oils and offers a promising preclinical approach for localized UC therapy.

Our previous research identified that an oral mPEG-b-PCL polymeric micelle (PM) maintained satisfactory integrity but exhibited limited transcytosis efficiency. To enhance transcytosis and enable ROS-responsive release, we developed a series of hybrid PMs by blending a synthesized L-carnitine-grafted, thioketal-linked LC-PEG5k-TK-PCL7k polymer with mPEG5k-PCL7k. These hybrid PMs, similar in particle size (120 nm) and drug loading (10

Current treatments for ulcerative colitis (UC) often fail to adequately address its multifactorial pathogenesis, which involves oxidative stress, barrier dysfunction, and gut microbiota dysbiosis. This study evaluated the therapeutic potential and multi-targeting mechanism of a ginseng, salvia root, and notoginseng oral solution (GSNS) in a mouse model of colitis induced by dextran sulfate sodium (DSS). Based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) technology, 25 major bioactive components were identified. Following the induction of colitis with 3.5% DSS in C57BL/6J mice, the animals were treated with the GSNS (40, 80, or 160 mg/kg/day) or 5-Amino Salicylic Acid (5-ASA). The therapeutic efficacy was assessed via disease activity, histopathological staining, cytokines and oxidative stress analysis, and a barrier integrity test. Combined data from Western blot, qPCR, immunohistochemistry, electron microscopy, and 16S rRNA sequencing indicate that the therapeutic effect of the GSNS against colitis is attributable to its dual role in dampening pro-inflammatory cytokines and potentiating antioxidant defenses via the Nrf2/HO-1 signaling pathway. It also upregulated Occludin expression, repaired tight junctions, and was associated with beneficial alterations in the gut microbiota, as evidenced by increased Prevotellaceae and suppressing Escherichia-Shigella. These findings demonstrated that the GSNS exerts a multi-target effect against colitis by synergistically enhancing antioxidant defense, repairing the intestinal barrier, and modulating microbial ecology, supporting its potential as a promising natural compound-based candidate for DSS-induced colitis treatment.

Disulfiram (DSF), an FDA-approved anti-alcoholism drug, has demonstrated potent anticancer activity against peritoneal carcinomatosis. However, its therapeutic potential is severely hampered by poor aqueous solubility and instability. Nanoemulsion system provides a promising platform to overcome these challenges. Herein, this study developed and optimized a DSF-loaded nanoemulsions (DSF-NE) to enhance the therapeutic efficacy of DSF in peritoneal carcinomatosis. The optimized DSF-NE exhibited several formulation advantages, including a small particle size (similar to 84 nm), narrow size distribution (similar to 0.1), high encapsulation efficiency (>90 %) and sustained-release behavior. Subsequently, cytotoxicity assays against MGC-803, SKOV-3 and Caco-2 cells revealed that DSF-NE significantly enhanced cytotoxic effects compared to DSF, with IC50 values reduced by 74 %, 62 % and 56 %, respectively. Consistently, DSF-NE achieved a tumor inhibition rate 108.57 % higher than that of DSF in a murine peritoneal carcinomatosis model. The main mechanism involves enhanced cellular uptake of DSF-NE, which promotes ROS generation and subsequently triggers apoptosis. Collectively, these findings highlight DSF-NE as a nanoformulation strategy that not only improves the therapeutic performance of DSF in peritoneal carcinomatosis but also offers broader implications in the development of effective delivery systems for poorly soluble and unstable drugs.

Colitis is considered a significant risk factor for the development and progression of colorectal cancer due to excessive inflammation formed as a result of inflammatory bowel disease (IBD), which is linked to colorectal cancer development. Colorectal cancer often lacks overt symptoms in its early stages, leading to late-stage diagnosis in most patients. Therefore, timely diagnosis and differentiation of colitis and colorectal cancer are crucial. This study introduces a novel activatable carboxylesterase 2 (CES2) fluorescent probe, DBF-CES2, consisting of a cationic indolium fluorophore and a CES2-specific benzyl ester recognition group. The probe operates via the intramolecular charge transfer (ICT) mechanism. Upon binding and hydrolysis by CES2, a potent electron- donating hydroxyl group is released, enhancing the ICT effect and increasing fluorescence intensity, emitting red fluorescence light (lambda em = 680 nm). The probe had a large Stokes shift of 167 nm and a detection limit as low as 0.70 ng/mL. It also had high selectivity, sensitivity, and biocompatibility. Cellular imaging experiments demonstrated that CES2 expression levels in colorectal cancer cells were higher than those in normal cells. The DBF-CES2 probe specifically recognized endogenous CES2 in colorectal cancer cells, promptly distinguishing them from normal cells. In vivo imaging in mice confirmed that the probe could differentiate between colitis and colorectal cancer, allowing for the assessment of the therapeutic effects of two drugs. The synthesized CES2targeting organic small molecule fluorescent probe DBF-CES2 is a new molecular tool for the early diagnosis of colitis and colorectal cancer-related diseases, holding significant potential in clinical diagnostics.

This study comprehensively investigated the effect of structural integrity on the oral delivery efficacy of mPEG-b-PCL polymeric micelles (PMs) using fluorescence resonance energy transfer (FRET) technology. During mucus penetration, the integrity loss of PMs resulted from the "hydration effect" of mucins and the "solubilization effect" of bile salts. Increasing surface PEG density or decreasing particle size <50 nm resisted the "hydration effect", while shortening PCL chain or increasing aggregation number alleviated the "solubilization effect". Fluorescence colocalization studies demonstrated that low surface PEG density and small particle size enhanced the cellular uptake of PMs, but high surface PEG density preserved the intracellular integrity of PMs. Approximately 30 %-60 % of endocytosed PMs were expelled within 4 h, correlating with their cellular uptake efficiency. Transcellular transport results indicated that 5 %-25 % of PMs underwent transcytosis within 4 h, 0.5 %-10 % of initial PMs remained intact. In situ intestine perfusion data confirmed the consistency between the in vitro findings and the actual performance of PMs in vivo. Two types of PMs were selected to encapsulate cyclosporine A (CyA) based on their enhanced integrity and transcytosis efficiency. The PM with a short amphiphilic block and loose structure exhibited comparable in vitro release and in vivo performance to Neoral®, with a Cmax of 1356.28 ± 170.01 ng/mL, a Tmax of 2 h, and an AUC0-t of 16,408.92 ± 1166.78 ng/mL*h. However, the PM with a long amphiphilic block and ordered core PCL arrangement exhibited sustained release of CyA both in vitro and in vivo, decreasing CyA accumulation in major organs and improving the oral bioavailability of CyA, with a Cmax of 757.07 ± 66.19 ng/mL, a Tmax of 9.33 ± 2.31 h, and an AUC0-t of 21,938.44 ± 2183.59 ng/mL*h.

Safe and effective Cu 2+ supplementation in local lesion is crucial for minimizing toxicity of DSF-based chemotherapy. Targeted delivery of Cu 2+ appears more promising. Intraperitoneal chemotherapy for peritoneal carcinoma (PC) establishes "face-to-face " contact between targeted nanocarriers and tumor tissue. Herein, this study developed a biodegradable, injectable thermosensitive hydrogel that coencapsulating DSF submicroemulsion (DSF-SE) and folate-modified liposome loading glycyrrhizic acid -Cu (FCDL). FCDL acted as 'beneficial horse ' to target the tumor -localized folate receptor, thus liberating Cu 2+ in tumor nidus. The prepared FCDL and DSF-SE were found with uniform sizes (160.2 nm, 175.4 nm), low surface charge (-25.77 mV, -16.40 mV) and high encapsulation efficiency (97.93 %, 90.08 %). In vitro drug release profile of FCDL, DSF-SE and FCDL &DSF-SE@G followed a sustained release pattern. And the release behavior of Cu 2+ from FCDL was pH -related, i.e., Cu 2+ was released faster under acidic condition. When FCDL and DSF-SE were loaded into an PLGA-PEG-PLGA-based hydrogel system, FCDL &DSF-SE@G was formed to ensure separated delivery of Cu 2+ and DSF in space but synchronized release over time. The rheology experiment showed a satisfactory gelling temperature of 32.7 degrees C. In vitro cytotoxicity study demonstrated that FCDL &DSF-SE@G significantly lowered the IC 50 of free Cu 2+ /DSF, Cu 2+ /DSF hydrogel and non -targeted analogue by almost 70 %, 65 % and 32 %, respectively. Accordingly, in tumor -bearing mice, FCDL &DSF-SE@G augmented the tumor inhibition rates for the same formulations by 352 %, 145 % and 44 %, respectively. The main mechanism was attributed to higher uptake of FCDL and DSF-SE, resulting in increased Cu(DDTC) 2 formation, ROS production and cell apoptosis. In conclusion, this targeted nanotherapy approach with dual-nanocarriers loaded hydrogel system, with its focus on face-to-face contact between nanocarriers and tumor tissues in the peritoneal cavity, holds significant promise for intraperitoneal chemotherapy in PC.

Curcumin, a naturally occurring poorly water-soluble polyphenol with a broad spectrum, is a typical BCS IV drug. The objective of this study was to develop curcumin nanocrystals liposomes with the aim of improving bioavailability. In this study, we prepared cationic curcumin nanocrystals with a particle size of only 29.42 nm; such a phenomenal range of particle sizes is very rare. Moreover, we summarized and evaluated the parameters of the nanocrystal preparation process, including methods, formulations, etc., and the rules we concluded can be generalized to other nanocrystal preparation processes. To counteract the instability of the nanocrystals in the digestive tract, cationic curcumin nanocrystals were loaded into negatively charged liposomes through gravitational force between different charges. Unexpectedly, chitosan oligosaccharide was found to promote the self-assembly process of curcumin nanocrystal liposomes. In vitro and in vivo experiments demonstrated that chitosan-modified curcumin nanocrystal liposomes exhibited enhanced resistance to enzyme barriers, mucus barriers, and cellular barriers, resulting in a 5.4-fold increase in bioavailability compared to crude powder formulations. It can be concluded that cationic nanocrystals liposomes represent an appropriate novel strategy for improving the dissolution rate and bioavailability of poorly soluble natural products such as curcumin.

To improve the oral absorption and anticancer efficacy of the BCS-IV drug etoposide (ETO), oral nanocrystal-loaded lipid carriers (Lipo@NCs) were developed in this study by modifying the BCS-IV drug nanocrystal with the lipid bilayer. The ETO-Lipo@NCs were prepared by the thin film hydration high-pressure homogenization method, and the core of positively charged ETO nanocrystals was prepared by the sonoprecipitation-high pressure homogenization method. The optimized ETO-Lipo@NCs were spherical particles with an average particle size of 220.3 ± 14.2 nm and a zeta potential of −9.95 ± 0.81 mV, respectively. The successful coating of a lipid bilayer on the surface of nanocrystals in ETO-Lipo@NCs was confirmed by several characterization methods. Compared to nanocrystals, the release rate and degree of Lipo@NCs in SIF were significantly decreased, indicating that the lipid bilayer can effectively prevent the rapid dissolution of core nanocrystals. ETO-Lipo@NCs demonstrated a significant improvement in the intestinal permeability and absorption of ETO in a single intestinal perfusion experiment. In the cells, ETO-Lipo@NCs showed enhanced cellular uptake and transepithelial transport compared with ETO nanocrystals. Pharmacokinetic analysis indicated that ETO-Lipo@NCs had a longer plasma half-life than ETO solution, and the oral bioavailability of ETO-Lipo@NCs was 1.96- and 10.92-fold higher than that of ETO nanocrystals and ETO coarse crystals, respectively. Moreover, the ETO-Lipo@NCs orally dosed at 10 mg/kg exhibited an excellent inhibitory effect against tumors in a subcutaneous Lewis lung carcinoma (LLC) xenograft model compared with other preparations. These results indicate that the Lipo@NCs formulation has an oral absorption-promoting effect of the BCS-IV drug ETO, which could warrant further application in the oral delivery of other poorly bioavailable drugs.

本试验旨在对院内制剂清胃片中挥发油的提取工艺进行研究,使清胃片挥发性成分提取完全,从而更好地发挥药物治疗作用.采用水蒸汽蒸馏法提取清胃片中的挥发油组分(木香、丁香和薄荷),以挥发油提取量、木香烃内酯和去氢木香内酯含量为指标,通过单因素考察、响应面设计试验确定药材中挥发油组分的最佳提取工艺.试验最终得到清胃片中挥发油的最佳提取工艺:药材加8倍量水,浸泡2 h,水蒸气蒸馏法提取7 h得挥发油组分.挥发油提取工艺准确、稳定、可靠,为清胃片中挥发油提取工艺的优化完善提供参考,可用于清胃片的批量生产,为其进一步开发利用提供有力支撑和理论依据.

本研究旨在提升元和正胃片的质量标准.采用TLC法对甘草进行鉴别;采用HPLC法测定甘草苷、甘草酸的含量,色谱条件如下,色谱柱:InertSustainSwift-C18;流动相:乙腈-0.05％磷酸,梯度洗脱;流速:1.0 mL/min;检测波长:237 nm;柱温:25℃.在TLC鉴别时,对照药材、对照品和样品图谱在对应位置显示相同的斑点,分离效果良好,对阴性样品无影响.甘草苷、甘草酸分别在0.003～0.024 mg/mL(R2=0.999 6)、0.012 49～0.099 93 mg/mL(R2=0.999 7)范围内与峰面积呈良好的线性关系,平均加样回收率分别为99.01％(RSD=1.53％)、99.16％(RSD=0.93％).薄层鉴别和含量测定方法简单、精确、专属性强、重现性好,可为元和正胃片质量标准的完善提供参考.

本研究采用高效液相色谱法(HPLC)建立了沙棘雨生红球藻胶囊中异鼠李素的含量测定方法.沙棘雨生红球藻胶囊内容物经95％乙醇提取后进行酸处理,使苷元充分水解为苷,采用InertSustainSwift-C18(4.6 mm×250 mm,5 μm)柱作为固定相;甲醇-0.4％磷酸溶液(56:44)作为流动相;流速为1.0 mL/min;检测波长为370 nm;柱温25℃;进样体积10μL.结果显示异鼠李素在0.004 38～0.011 68 mg/mL的质量浓度范围内线性关系良好(R2=0.999 4),回收率在96.43％～98.98％范围内,RSD=0.89％(n=6).该方法测得3批产品中异鼠李素的含量均值为45.26mg/100g(n=9).该测定方法准确高效、简单易行,可为沙棘雨生红球藻胶囊中异鼠李素的含量测定提供参考.

本研究优选降血脂片成型工艺,以成型率、脆碎度及崩解时间为评价标准,在单指标试验后,采用星点设计-效应面法优选辅料配比、崩解剂用量等参数,结果显示降血脂片的最佳成型工艺为辅料玉米淀粉、聚乙二醇6000按1.5∶1配比,辅料干浸膏粉、辅料按1.2∶1配比,乙醇体积分数70％,羧甲基淀粉钠用量3.8％,交联羧甲基纤维素钠用量2％,总评"归一值"为0.851 4.采用星点设计-效应面法优选的成型工艺合理可行,具有很好的实用性和预测性,可为制剂后续质量研究提供依据.

本研究优化了黄芪丹香颗粒的成型工艺.以稀释剂用量比例、润湿剂浓度和润湿剂用量作为考察因素,以成型率、吸湿率和休止角作为评价指标,在单因素考察试验的基础上,应用Box-Behnken响应面设计结合G1-熵权法优选黄芪丹香颗粒的成型工艺.结果得到最优成型工艺为糊精与干膏粉的比例是0.8∶1,以90.5％的乙醇溶液作润湿剂,用量为混合粉重量的22％.验证试验中颗粒的成型率、吸湿率和休止角分别为92.41％、9.93％和29.7°,综合评分为95.69,与预测值接近.结果表明优选的成型工艺稳定可行,可为黄芪丹香颗粒的工业化生产提供依据.

以教学内容为载体,开展药剂学课程思政探索.深入挖掘药剂学课程蕴含的思政元素及两者间的融合点,建立有助于培养学生爱岗敬业、科学精神、科学思维、职业道德和工匠精神的思政案例库,使学生掌握药剂学基本知识和基本技能,引导学生形成良好的职业素养.

Purpose: Non-small cell lung cancer (NSCLC) is an aggressive tumor with high mortality and poor prognosis. In this study, we designed a liposome encapsulating polymeric micelles (PMs) loaded with vinorelbine (NVB) and cis-diamminedichloroplatinum (II) (cisplatin or CDDP) for the treatment of NSCLC. Materials and Methods: Sodium poly(alpha-L-glutamic acid)-graft-methoxy-polyethylene glycol (PLG-G-PEG 5K ) was used to prepare NVB-loaded NVB-PMs and CDDP-loaded CDDP-PMs that were co-encapsulated into liposomes by a reverse evaporation method, yielding NVB and CDDP co-delivery liposomes (CoNP-lips) composed of egg phosphatidyl lipid-80/ cholesterol/DPPG/DSPE-mPEG(2000) at a molar ratio of 52:32:14:2. The CoNP-lips were characterized in terms of particle size, zeta potential, drug content, encapsulation efficiency, and structural properties. Drug release by the CoNP-lips as well as their stability and cytotoxicity was evaluated in vitro, and their antitumor efficacy was assessed in a mouse xenograft model of Lewis lung carcinoma cell-derived tumors. Results: CoNP-lips had a spherical shape with uniform size distribution; the average particle size was 162.97 +/- 9.06 nm, and the average zeta potential was -13.02 +/- 0.22 mV. In vitro cytotoxicity analysis and the combination index demonstrated that the CoNP-lips achieved a synergistic cytotoxic effect at an NVB:CDDP weight ratio of 2:1 in an NSCLC cell line. There was sustained release of both drugs from CoNP-lips. The pharmacokinetic analysis showed that CoNP-lips had a higher plasma half-life than NP solution, with 6.52- and 8.03-fold larger areas under the receiver operating characteristic curves of NVB and CDDP. CoNP-lips showed antitumor efficacy in tumor-bearing C57BL/6 mice and drug accumulation in tumors via the enhanced permeability and retention effect. Conclusion: CoNP-lips are a promising formulation for targeted therapy in NSCLC.

Introduction: Etoposide refers to a derivative of podophyllotoxin, which plays an impor-tant role in the treatment of cancer due to its prominent anti-tumor effect. As a BCS IV drug, etoposide exhibits insufficient aqueous solubility and permeability, thereby limiting its oral absorption. To enhance the oral bioavailability of etoposide, this study developed an amorphous nanopowder. Methods: Based on preliminary screening and experimental design, the stabilizer and preparation process of etoposide nanosuspension were explored. Subsequently, using a Box-Behnken design, the effects of independent factors (ultrasonication time, ratio of two phases and stabilizer concentration) on response variables (particle size and polydispersity index) were studied, and then the formulation was optimized. Finally, nanosuspension was further freeze dried with 1% of mannitol resulting in the formation of etoposide amorphous nanopowder. Results: The optimized etoposide nanopowder showed as spherical particles with an average particle size and polydispersity index of 211.7 +/- 10.4 nm and 0.125 +/- 0.028. X-ray powder diffraction and differential scanning calorimetry confirmed the ETO in the nanopowder was amorphous. Compared with coarse powder and physical mixture, etoposide nanopowder achieved significantly enhanced saturated solubility and dissolution in various pH environments. The C-max and AUC(0-t) of etoposide nanopowder after oral administration in rats were respectively 2.21 and 2.13 times higher than the crude etoposide suspension. Additionally, the T-max value of nanopowder was 0.25 h, compared with 0.5 h of reference group. Discussion: In the present study, the optimized amorphous nanopowder could significantly facilitate the dissolution and oral absorption of etoposide and might act as an effective delivery method to enhance its oral bioavailability.

主要探究五味子酸枣仁软胶囊对改善动物睡眠功能的影响.选取SPF级KM雌性小鼠48只(体重18.00～22.00 g).试验设4组,包括高、中、低3个剂量组和1个阴性对照组,高剂量组为1.00 g/kg(相当于成人每日用量的30倍)、中剂量组为0.33 g/kg(相当于成人每日用量的10倍)、低剂量组为0.17 g/kg(相当于成人每日用量的5倍)、阴性对照组为玉米胚芽油.小鼠每日灌胃给予受试样品1次,灌胃用量20 mL/kg,连续30d.通过直接睡眠试验、延长戊巴比妥钠睡眠时间试验、戊巴比妥钠阈下剂量睡眠试验、巴比妥钠睡眠潜伏期试验,探究该样品对改善动物睡眠功能的影响.结果 表明,在该试验条件下,延长戊巴比妥钠睡眠时间试验、戊巴比妥钠阈下计量睡眠时间试验、巴比妥钠睡眠潜伏期3项试验中两项呈阳性,且无明显直接睡眠作用.根据《保健食品检验与评价技术规范》中改善睡眠功能检验方法,可判定该样品具有改善睡眠功能.

研究保肝软胶囊对化学性肝损伤小鼠体重变化以及相关生化指标的影响.采用酒精肝损伤模型,选取SPF ICR级雄性小鼠(体重18～22g),分别经口给予相当于成人摄入量5、10、30倍的保肝软胶囊即0.25、0.50、1.50g/(kg·d),连续灌胃30d,进行各项生化指标检测及组织病理学检查.结果 显示,高剂量组具有降低肝组织中丙二醛、甘油三酯,升高还原型谷胱甘肽含量的作用;高剂量组脂肪变性评分低于模型对照组,而且样品对实验动物体重未见明显影响.试验结果表明,保肝软胶囊对化学性肝损伤具有辅助保护功能.