Rhabdomyolysis-induced acute kidney injury (RM-AKI) is a life-threatening clinical condition characterized by excessive myoglobin release, leading to kidney tubular obstruction, oxidative stress, and iron-mediated lipid peroxidation. However, current therapies fail to effectively suppress oxidative stress cascades and lack kidney targeting. Herein, we developed a kidney-targeted nanodrug delivery system with multimodal antioxidant functionality (DFO@SOC) for RM-AKI therapy. Using antioxidant capacity as the decisive screening criterion, Se/S co-doped onion-derived carbon dots (SOC) were identified as the optimal nanocarrier through systematic natural polyphenol precursor selection and heteroatom-doping optimization. SOC exhibited pronounced superoxide dismutase-like and catalase-like activities. The iron chelator deferoxamine (DFO) was subsequently loaded onto SOC, yielding uniformly sized, negatively charged DFO@SOC nanoparticles. In vitro studies demonstrated efficient cellular uptake, robust intracellular scavenging of reactive oxygen species (ROS) and iron ions, and negligible cytotoxicity. In an RM-AKI mouse model, DFO@SOC selectively accumulated in injured kidneys. Notably, Sound Touch Visco-elastography (STVi) and Quantitative Tissue Scattering Coefficient (QTSC) enabled noninvasive and real-time evaluation of therapeutic efficacy with kidney stiffness decreasing significantly from ∼14 to 7 kPa. Combined biochemical and histopathological analyses, DFO@SOC treatment significantly reduced Scr from ∼193.31 to ∼93.82 μmol/L and blood urea nitrogen (BUN) from ∼52.99 to ∼30.68 mmol/L compared to the model group. In summary, the synergistic antioxidant and iron-chelation effects of DFO and SOC, establishing DFO@SOC as a promising nanotherapeutic strategy for RM-AKI.

BackgroundTitanium dioxide (TiO2) is widely used as a white additive in food and pharmaceuticals, but its safety has raised increasing concerns. Currently, calcium carbonate is commonly used as an alternative to TiO2 in white film coatings, although it provides inferior whiteness. With the development of the health industry, TiO2-free and pigment-free white tablet coatings are becoming more desirable.MethodsInspired by white beetle scales, porous films were fabricated via phase separation between polyvinyl alcohol (PVA) and polyethylene glycol (PEG). The refractive index difference between polymer and air generated strong light scattering. Light-shielding effect of calcium carbonate of different morphologies was further investigated.ResultsUnder the same type of calcium carbonate as the opacifier, porous PVA/PEG films showed CIELab whiteness all above 80 (up to 87), much higher than the dense films using lipid plasticizers. With the same porous structure, quasi-rhombohedral calcium carbonate increased whiteness by 8.2% compared with spindle aggregates.ConclusionsPorous structures dominated whiteness improvement. Bioinspired porous films via polymer-polymer phase separation represented a novel strategy for TiO2-free white tablet coating, and could guide the screening of other phase-separating polymers to further improve the film whiteness and properties.

Oxidative stress triggered by excessive accumulation of reactive oxygen species (ROS) in vivo represents a common pathological basis for various diseases. Therefore, the development of safe and efficient antioxidants to eliminate excess ROS and counteract oxidative stress holds significant research potential. In recent years, carbon dots (CDs) have emerged as a novel class of carbon-based nanomaterials whose antioxidant activity has attracted widespread attention due to their excellent biocompatibility, low toxicity, and ease of functionalization, offering new strategies to combat oxidative stress. Although numerous excellent reviews on CDs have been published, there is still a lack of systematic review specifically focused on antioxidant CDs. This article summarizes the primary antioxidant mechanisms of CDs, including free radical scavenging, enzyme-like activities, and regulation of cellular signaling pathways. Furthermore, strategies for enhancing the antioxidant activity of CDs are discussed from the perspectives of synthesis process optimization, functional design, selective radical scavenging, and stimulus-responsive regulation, providing new insights for the design of more effective antioxidant CDs. Recent advances in the biomedical applications of antioxidant CDs are reviewed. Additionally, the in vivo metabolism, biodegradation, and biosafety of CDs are discussed. Finally, current challenges in this field are addressed, and future development prospects are outlined

Background: Although peptides are widely used in the clinical treatment of various diseases due to their strong biological activity, they usually require frequent injections owing to their poor in vivo half-life. Therefore, there is a strong clinical need for sustained peptide formulations. Methods: In this study, liraglutide (Lir) and biocompatible multivesicular liposomes (MVLs) were utilized as the model drug and sustained-release carriers, respectively. The drug release rate of Lir-MVLs was controlled by changing the ratio of SPC and DEPC with different phase transition temperatures (PTT, PTTSPC = −20 °C, PTTDEPC = 13 °C). Results: As the SPC ratio increased, Lir-MVLs had more flexible lipid membranes, poorer structural stabilization, and fewer internal vesicles with larger particle sizes, contributing to faster release of Lir. After subcutaneous injection of Lir-MVLs, the blood glucose concentration (BGC) of db/db mice decreased to different levels. When the SPC-DEPC ratio was greater than 85:15, the drug release rate was too fast; the BGC remained below 16 mM for only 2–4 days, while when the drug release rate was too slow, was the case when the SPC-DEPC ratio was less than 50:50, the BGC also remained below 16 mM for only 2–3 days. However, when the SPC-DEPC ratio was 75:25, the BGC could be maintained below 16 mM for 8 days, indicating that the release properties of this ratio best met the pharmacological requirements of Lir. Conclusions: This study investigated the effects of phospholipids with different PTT on the release characteristics of Lir-MVLs, and provided ideas for the design of sustained-release peptide preparations.

为了提高植物甾醇在体内的生物利用度,促进其在医药中的广泛应用,在制备的植物甾醇液体自微乳基础上,进一步利用喷雾干燥制备固体自微乳,以提高其长期储存稳定性.首先筛选了载体材料的种类和用量,然后以集粉率为考察指标,在单因素实验的基础上进行响应面优化,确定喷雾干燥的最优工艺参数.结果表明,最优载体为胶体二氧化硅,在载体与自微乳的质量比为1:1、喷雾干燥的进风温度为120℃、进料速度10mL/min、进风流量540L/h,此时得到的集粉率为49.36％,与理论预测值基本一致.制得的S-SMEDDS为白色粉末,平均载药量为1.00％,重新分散在水中能形成淡蓝色澄清透明的乳液,再分散粒径为27.20±1.15nm,多分散系数为0.137±0.010.药物以无定形的状态被吸附在胶体二氧化硅的孔径中,在不同的pH条件下,释放度有所不同,但与原料药相比,释放效果有了很大改善.

The application of saponins has been restricted by problems such as hemolysis, low bioavailability, and poor solubility. So it is imperative to find a strategy to deliver saponins safely and efficiently. Here, through bottom-up technique, we design and prepare two saponin-cholesterol (Cho) nano-complex: dioscin (Dio, steroid saponin)-Cho nanofibers (NFs) and escin Ia (EIa, triterpene saponin)-Cho nanoparticles (NPs). It is found that the hydrophobic force and hydrogen bonding drive the two pairs of molecules to bind in different directions (the 3β-OH of Cho face the sugar chain of EIa and the 22α-O of Dio, respectively) and finally show spherical NPs (EIa-Cho) and fibrous NFs (Dio-Cho). The equimolar saponin-Cho complex, Dio NFs and EIa NPs, reveal potent cytotoxicities against mouse breast cancer cells (4T1) in vitro. In vivo results confirm the antitumor (4T1 mice model) efficacy of PEGylation Dio NFs (10 mg/kg, i.v.) with a tumor inhibition rate of 61%, meanwhile, it does not cause extreme irritation and pain as free Dio does to mice. Moreover, compared with the free drug, the prepared nano-complex can significantly reduce hemolysis and organ toxicity. Our research reduces the toxicity of saponins while retaining their antitumor activity, providing a new strategy for the delivery of saponins.

Thermo-chemotherapy could improve the therapeutic effects of single chemotherapy with the help of cytotoxic heat produced by the PTT (photothermal therapy). The photothermal conversion property of material needs to be preferentially considered in the design the drug delivery in the thermo-chemotherapy. Therefore, in this work, mesoporous carbon nanoparticles (MCN) with excellent heat generating efficiency and high surface area was designed. And the NIR absorbing dye cypate was conjugated on the surface of MCN by the cleavable disulfide bonds to hinder the premature release of doxorubicin (DOX) and enhance the photothermal properties of MCN-based delivery systems. And then TPGS was further covered on the surface of MCN by hydrophobic force to prolong circulation time and improve the biocompatibility and dispersion stability of MCN-CyT in physiological environment. The release of DOX accelerated obviously in the presence of glutathione (GSH), acidic condition and NIR irradiation, indicating that DOX/MCN-CyT exhibited redox/pH/NIR triple-triggered drug release. The anti-tumor experiment indicated that DOX/MCN-CyT showed a synergistic thermo-chemotherapy effect for cancer. Thus, the present research provides huge potential in multi-triggered drug delivery and thermochemotherapy for combination therapy.

为顺应时代发展,满足药企对复合应用型人才的需求,沈阳药科大学对新工科背景下药学综合实践教学活动进行了改革.实践教学是培养药学人才的工程实践能力和创新能力的重要环节.但是由于制药行业的特殊性,学生在生产实习过程中进入核心车间学习的时间较短,多属于认识性实习,难以满足实践教学的需要,也无法达到制药工业对工程人才实践能力的要求.因此发展GMP实训教育势在必行.文章旨在探讨新工科背景下,依托于GMP实训中心的药学工程类实践课程的改革和规范化管理方式.通过构建多层次GMP实训教学体系、虚拟仿真教学平台、增设劳动课、开展多元化实践教学活动,培养学生实践创新能力和优良品性.实践课程的规范化管理要通过建立科学的课程考核制度和合理的课堂管理制度实现,同时要配合建立完善的中心管理制度,保障中心高效、有序运转,进而全面提升教学质量.

对纳米胶束聚合物载体进行结构修饰,不仅可以使难溶药物增溶,还可以使载药载体在肿瘤组织聚集.本文以紫杉醇(PTX)为模型药物,合成了以二硫键(-S-S-)和油酸(OA)修饰后的聚乙二醇1 000维生素E琥珀酸酯(TPGS)与脱氧胆酸钠(NADC)按不同摩尔比制成混合胶束,并合成了以硫醚键修饰的TPGS与NADC混合胶束进行对比研究.主要考察了修饰后聚合物的临界胶束浓度(CMC)值,TPGS-OA与NADC不同摩尔比对胶束的理化性质的影响,对比二硫键和硫醚键氧化还原敏感释药的能力.结果 表明,当TPGS-OA与NADC的摩尔比减小,载药量增加,但稳定性降低;当摩尔比为3∶1时,TPGS-S-S-OA/NADC混合胶束的粒径、电位和包封率分别为96.24±2.42 nm、-24.4 mV和(98.7±0.08)％,混合胶束的溶血率在2％以下;二硫键修饰的混合胶束中PTX在10 mmol·L-1 H2O2介质(pH 7.4)5 h内释放96％,其与硫醚键修饰后的释药能力相当,但在低pH值(pH 5.5)介质中胶束的稳定性降低.所有动物实验均符合伦理学标准,并获得沈阳药科大学动物实验中心批准(No.211002300032403).本研究制备的稳定纳米胶束载体可在肿瘤异质环境中靶向释药.

目前我国制药技术处于高速发展的态势,制药行业对人才的要求也在不断提高,作为培养精通药学、化学、工程学多学科复合实践型人才的制药工程专业也面临着一系列挑战.文章结合沈阳药科大学及其他高校现状,对展现制药工程专业特色的实践教学进行分析,以期能够从实践教学角度为制药工程专业发展提供借鉴和启示.

Glutamic acid modified Pluronic P123 (P123-G) was synthesized to coat hydrophobic mesoporous silica nanoparticles (PGMSN) aiming to target large amino acid transporter 1 (LAT1) overexpressed cancer cells. We discovered that, once internalized, PGMSN could be transported out of the cells with their cargo, and the exported nanoparticles were then taken up by neighboring cells. This intercellular delivery of particles led to a deeper tumor penetration, presumably through tandem cycles of LAT1 mediated endocytosis and exocytosis. Taking advantage of high drug loading capability of MSN, a kind of cyanine dye Cypate acting as a photothermal converting agent was loaded into MSN along with the chemotherapeutic drug doxorubicin hydrochloride (DOX) to improve the anti-cancer effect by the combination of chemotherapy and photothermal therapy (PTT). Both DOX and Cypate stably dispersed in the pores of MSN, and the coating of P123-G serving as diffusion barrier blocked drug preleakage. The system possessed pH and near-infrared (NIR) light dual-responsive DOX release property. Additionally, PGMSN exhibited targeted PTT effect which strengthened cytotoxic activity of the system due to the enhanced endocytosis. So the deep tumor penetration and targeted PTT effect made PGMSN especially suitable for cancers overexpressing LAT1 receptors.

Barrigenol-like triterpenoids (BATs) showed promising anti-tumor, anti-inflammatory and anti-Alzheimer's activities, while, the inhibitory strength was usually affected by their states with aglycones or glycosides. In order to find more BATs as new anti-tumor agents with much more efficiency, the chemical and pharmaceutical studies were carried out on the acid hydrolysate product (AHP) of Semen Aesculi crude extract. Thirteen BATs, including three new aglycones (1-3), two new glycosides (4, 5) and eight known glycosides (6-13) were obtained. Compound 1, as the main product in AHP, with a tigloyl unit linked at the C-16 position was an unusual aglycone. All compounds exhibited various degrees of inhibitory activity against human breast cell line (MCF-7) and cervical cancer cell line (HeLa) growth, moreover, new aglycones 1 and 2, and the known glycoside 6 (escin Ia) and 9 were found to exhibit potent inhibitory activity which were similar to the positive control (doxorubicin hydrochloride). Compound 1, named 16-tigloyl-O-protoaescigenin, could suppress tumor progression and decreased lung metastasis focuses in mice, and no pathological change was observed at the end of the treatment course. Besides that, the hemolysis experiment between 1 and 6 revealed that the hemolysis toxicity of 1 was much less than that of 6. According to these results, 16-tigloyl-O-protoaescigenin, with the powerful anti-tumor activity and cancer cell apoptosis induction, might be considered as a new promising anti-tumor agent.

Cassane diterpenoids (CA) are considered as the main active constituents of medicinal plants belonging to the Caesalpinia genus. Three cassane derivatives, bonducellpin G (BG), 7-O-acetyl-bonducellpin C (7-O-AC) and caesalmin E (CE), isolated from Caesalpinia minax Hance seeds, showed strong anti-inflammatory activity. In this paper, pharmacokinetics (BG, 7-O-AC, CE) and tissue distribution (7-O-AC, CE) properties were studied for the first time using a reliable, sensitive and rapid UHPLC-Q-Orbitrap HR-MS to develop new anti-inflammatory agents. A novel quantitative method with full scan in positive ion mode was used to determine the contents of compounds. They were separated using acetonitrile-water (0.1% formic acid) as gradient mobile phase. The calibration curve displayed good linearity and the lower limit of quantitation was 0.005-0.02 μg/mL for all analytes. Meanwhile, the absorption, distribution, metabolism, excretion (ADME) property was predicted using PreADMET web. The pharmacokinetic parameters indicated that they were absorbed quickly, eliminated rapidly together with high blood concentration. The results of tissue distribution demonstrated that CE was distributed rapidly and widely among tissues, and stomach was the main tissue site of CE and 7-O-AC, followed by small intestine/liver. This study indicates that the structures and dosages of active CA should be modified to help improve the absorption rate and residence time, and the findings are helpful for the pharmaceutical design of CA derivatives.

In this research, a novel method was used to successfully stably coat Pluronic P123 on mesoporous silica nanoparticles (MSNs). Co-constructing a drug delivery system (DDS) with P123 and MSNs has not been previously reported. In this DDS, the coating of P123 was realized through a hydrophobic interaction with octadecyl chain-modified MSNs. The experiments found only Pluronic with an appropriate ratio of hydrophilic and lipophilic segments could keep the nanoassemblies stable. For comparison, nanoassemblies consisting of P123 and octadecyl chain-modified MSNs with or without a disulfide bond were prepared, which were denoted as PSMSNs and PMSNs, respectively. The disulfide bond was expected to endow the system with redox-responsiveness to enhance the therapeutic effect meanwhile decreasing the toxicity. A series of experiments including characterization of the nanoparticles, in vitro drug release, cell uptake and cellular drug release, in vitro cytotoxicity, cell migration and biodistribution of the nanoparticles were carried out. Compared with the PMSNs, PSMSNs displayed a redox-responsive drug release property not only in in vitro release text, but also on the cellular level. In addition, the cell migration experiments proved that the coating of P123 endowed the system with the ability of anti-metastasis. The accumulation of P123 in the tumor was enhanced after coating the MSNs by virtue of the 'EPR' effect of nanoparticles compared with the solution form.

"Gate" engineered mesoporous silica nanoparticles (MSN) have been extensively applied in cancer theranostics. Due to the complexity of tumor development and progression, with chemotherapy alone, it has often been difficult to achieve a good therapeutic effect. Currently, it has been shown that the combination with photothermal therapy overcomes the shortcoming of chemotherapy. In most studies, the photothermal effect has proven to accelerate drug release from nanocarriers and ablate malignant cells directly, but the influence on the intracellular fate of nanocarriers remains unknown. Herein, a lipophilic cyanine dye Cypate acting as a photothermal converting agent was conjugated on the external surface of MSN through a disulfide bond (MSN-Cy) and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) was coated on the outside of the MSN-Cy via a hydrophobic interaction (TCMSN) to cover the pores, preventing drug preleakage in the circulation. The TCMSN underwent exocytosis through the lysosome-mediated pathway. Moderate heat induced by near-infrared light promoted lysosome disruption, which thus partly inhibited lysosome-mediated particle exocytosis. In the meantime, TPGS, as a P-glycoprotein inhibitor, blocked the drug efflux. This research elaborated the photothermal effect from a new perspective-inhibiting particle exocytosis. The as-designed "gate" engineered MSN realized a double inhibition of drug efflux and particle exocytosis from cancer cells, thus sustaining the drug action time and enhancing the antitumor activity.

Thermochemotherapy exhibits a synergistic therapeutic efficiency for cancer, and the sensitivity of cancer cells to chemical drugs could be increased to a large extent at elevated temperature. In this work, a biocompatible nanocomposite thermosensitive mesoporous carbon nanoparticles (TSMCN) was prepared by covering a liposome on mesoporous carbon nanoparticles (MCN). The TSMCN had good photothermal efficiency and photostability. The doxorubicin (DOX)-loaded TSMCN (DOX/TSMCN) showed a slower release than the DOX-loaded MCN-COOH (DOX/MCN-COOH) both in simulated tumor environment and physiological environment. And release curves of DOX/TSMCN exposed to NIR laser exhibited the fast release property. The confocal laser scanning microscopy results illustrated that cellular uptake of DOX for DOX/TSMCN can be enhanced by NIR laser. The temperature of the tumor site reached up to 51.9 °C within 3 min after exposure to laser at 1.25 W/cm2 power density, which is above the phase transition temperature ( Tm) of liposome (40.7 °C). The biodistribution of DOX in vivo indicated that NIR laser can prolong the retardation time of DOX in the tumor site. The results of both 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and antitumor efficiency elucidated that the DOX/TSMCN under NIR irradiation had a synergistic therapeutic effect for cancer. Thus, the TSMCN could be explored as a powerful nanoplatform that shows great prospect in thermochemotherapy of tumor therapy.