Rheumatoid arthritis (RA) is a chronic autoimmune disease triggered by multiple factors, with a vicious cycle of "inflammation-oxidative stress-exacerbated inflammation". The use of conventional RA drugs is limited due to poor efficiency or side effect. Effective and rational treatment of RA remains a significant challenge. Based on traditional Chinese medicine experience and recent pharmacology study, it is essential to simultaneously inhibit immune-inflammatory responses and remodel the RA microenvironment. In this regard, this study developed a "carrier-free" nanocomplex (Cel@PFA NP) composed of natural-sourced celastrol (Cel) and natural-derived poly (ferulic acid) (PFA) to treat RA. PFA not only act as drug carrier, but also can exert antioxidant effect (T-AOC of 20 mg/mL PFA NP: 0.64 +/- 0.02 mM). By encapsulation, Cel@PFA NP improves Cel water solubility and reduces Cel toxicity. In addition, PFA can be degraded by enzyme in the RA microenvironment, on-demand releasing Cel and ferulic acid, exerting stronger antioxidant effects to restore endothelial dysfunction and inhibiting inflammatory cells, synergistically impeding RA progression. This study provides a novel approach for the application of natural active compounds with certain toxicity, offers new directions for the development of nanocarriers, and presents a new strategy for multi-target synergistic treatment of RA.

Arthritis is a joint inflammatory disease with multiple types that significantly compromises patients' quality of life. Current therapeutic efficiency is frequently constrained by the necessity for high dosages, the requirement for frequent administration, substantial side effects, and the risk of drug resistance. New therapeutic strategies are urgently needed. Melittin (Mel), a principal component of bee venom, has potent anti-inflammatory properties; however, its clinical application is limited by its hemolytic activity. To overcome the shortage, we developed targeted nanoparticles carrying Mel (MSC@NP-FA) with 68.3 ± 1.8% encapsulation efficiency, which were loaded within a microneedle (MN) to create MSC@NP-FA-MN. This strategy allows for precise anti-inflammatory therapy while reducing the risk of hemolysis. Both in vitro and in vivo studies demonstrated that MSC@NP-FA has lower hemolytic activity than Mel (p < 0.0001) and can target inflammatory macrophages to exert anti-inflammatory effects. In vitro transdermal test showed that more nanoparticles were delivered by the MNs (84.32 ± 6.97%) than bare nanoparticles (26.30 ± 2.55%) within 24 h. Furthermore, MSC@NP-FA-MN exhibited significant therapeutic efficacy without systemic toxicity or skin irritation in an adjuvant-induced arthritis (AIA) mouse model. Our findings highlight MSC@NP-FA-MN as a promising drug delivery system and suggest a new approach for safe and precise arthritis treatment.

CONTEXT:Chewable tablet palatability significantly impacts patient compliance, but current pharmacopeias have no standardized evaluation methods. This requires developing an objective system for assessing the palatability of chewable dosage forms, which will aid in setting quality control standards. OBJECTIVE:Using a texture analyzer, this study aimed to develop an objective, data-driven approach to evaluate chewability and grittiness in chewable tablets. METHODS:10 commercially available chewable tablet formulations were assessed, with subjective sensory evaluations supplemented by texture analysis-based measurements to quantify attributes of chewability and grittiness. To evaluate chewability, measurements of axial compression force, work, and adhesion were conducted, establishing optimal conditions of 400 N, 3 mm, and 50% strain to simulate oral chewing. For grittiness, a correlation between particle size and linear distance value was demonstrated, with Calcium carbonate used as a reference material to establish a standardized evaluation scale. RESULTS:Results indicated a strong correlation between tablet formulations and their sensory and texture analysis scores, with stickiness largely influenced by formulation ingredients such as milk powder and cacao powder. And the particle size of the insoluble material in the tablets largely influences the grit sensation. CONCLUSION:We developed a novel data-driven approach that offers a standardized assessment system to evaluate palatability characteristics in chewable tablets, facilitating more consistent formulation comparisons and potential optimization for consumer acceptability. This approach highlights the utility of texture analysis in transitioning empirical palatability assessments to objective, quantifiable methods, which may extend to other oral dosage forms.

Gels constitute a versatile class of materials with considerable potential for applications in both technical and medical domains. Physicochemical property characterization is a critical evaluation method for gels. Common characterization techniques include pH measurement, structural analysis, mechanical property assessment, rheological analysis, and phase transition studies, among others. While numerous research articles report characterization results, few reviews comprehensively summarize the appropriate numerical ranges for these properties. This lack of standardization complicates harmonized evaluation methods and hinders direct comparisons between different gels. To address this gap, it is essential to systematically investigate characterization methods and analyze data from the extensive body of literature on gels. In this review, we provide a comprehensive summary of general characterization methods and present a detailed analysis of gel characterization data to support future research and promote standardized evaluation protocols.

The underlying mechanism of how natural musk treats Bell's palsy is not clear. This study aims to reveal the potential mechanism of musk in treating peripheral nerve injury in vitro. To achieve this, an oxidative stress injury model was established in Schwann cells (SCs) using cobalt chloride (CoCl2). To assess the protective effects of Muscone (Mus) on this injury and explore its mechanism, cell viability assays, siRNA transfection, enzyme-linked immunosorbent assays (ELISA), quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting, immunofluorescence staining, and ultrastructural analysis of cells were employed. As a result, it is indicated that Mus intervention enhanced SC proliferation and S-100b mRNA under hypoxia, while also reducing reactive oxygen species (ROS) and elevating superoxide dismutase (SOD) levels. Mus ameliorated oxidative stress and inflammation in hypoxic SCs by reducing IL-1β and TNF-α. Furthermore, Mus modulated key indicators involved in oxygen metabolism, cell repair, and neurometabolism, including C-JUN and GDNF. IL-1R1, localized to the SC membrane, was upregulated by hypoxia but significantly downregulated following Mus intervention. Mus also inhibited the expression of NF-κB pathway components (IRAK1, IKK, p65, p50) and increased IκB-α. Critically, abolishing IL-1R1 expression via siRNA knockdown showed a consistent effect with Mus. It is concluded that by suppressing IL-1R1, Mus attenuated inflammation in hypoxic SCs through inhibition of the NF-κB pathway. This study indicated IL-1R1's role in hypoxia-induced SC dysfunction. Furthermore, Mus might be a potentially effective medicinal for treating Bell's palsy.

This study aims to investigate the effects of the relative humidity and formulation ratio on the hygroscopicity, tableting performance, and physical stability of polyols (mannitol and xylitol) as fillers in chewable tablets. To address the issues of hygroscopicity and sticking during tableting of chewable tablets containing polyol fillers, a systematic analysis was conducted by adjusting the ratio of mannitol and xylitol, and adding magnesium stearate (Mgst) as lubricant. The study investigated changes in hygroscopicity of the powder blends, tablet compressive force (F), and increment in ejection force (DEF) under varying humidity and formulation conditions. The porosity, tensile strength, and disintegration time of the tablets were also measured and analyzed to investigate the effects of humidity and formulation factors on tablet quality. The results indicate that increasing the mannitol content significantly reduces the hygroscopicity and moisture content of the powder blends. Higher levels of Mgst and mannitol improve the sticking issues in compression. However, an increase in mannitol content may decrease tablet porosity, leading to a longer disintegration time. Under high humidity conditions, increasing the amounts of mannitol can reduce the polymorphic transformation tendency of xylitol and enhance the hardness stability of the chewable tablets. This study reveals the significant effects of relative humidity and the mannitol-xylitol ratio on powder hygroscopicity, compaction performance, and tablet quality, providing a theoretical basis for optimizing formulations containing polyol fillers under controlled humidity conditions. The findings offer important references for adjusting process parameters in actual production, with particular guidance on improving tablet physical stability, anti-sticking performance, and disintegration control. (c) 2024 Published by Elsevier B.V. on behalf of The Society of Powder Technology Japan. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

The silkworm cocoon (SC), both as a traditional Chinese medicine and as the raw material for biocompatible carriers, has been extensively used in the medical and biomedical fields. This review elaborates on the multiple functions of SC, with an in-depth analysis of its chemical composition, biological activities, as well as its applications in modern medicine. The primary chemical components of SC include silk fibroin (SF), silk sericin (SS), and other flavonoid-like bioactive compounds demonstrating various biological effects. These include hypoglycemic, cardioprotective, hypolipidemic, anti-inflammatory, antioxidant, and antimicrobial actions, which highlight its potential therapeutic benefits. Furthermore, the review explores the applications of silk-derived materials in drug delivery systems, tissue engineering, regenerative medicine, and in vitro diagnostics. It also highlights the progression of SC from laboratory research to clinical trials, emphasizing the safety and efficacy of SC-based materials across multiple medical domains. Moreover, we discuss the market products developed from silk proteins, illustrating the transition from traditional uses to contemporary medical applications. This review provides support in understanding the current research status of SC and the further development and application of its derived products.

Background and objectives: In ancient China, bee venom was widely used to treat various diseases. Although using bee venom is not currently a mainstream medical method, some have applied it to treat certain conditions, including idiopathic facial paralysis (IFP). Recently, melittin (Mel), the main active component of bee venom, has been shown strong anti-inflammatory and analgesic effects. However, how bee venom improves neurological dysfunction in facial paralysis remains unknown. This study aimed to investigate the anti-neurotraumatic effect of Mel on Schwann cells (SCs), the main cells of the neuron sheath, injured by oxidative stress. Methods: A model of hypoxic SCs was established, and CCK-8 assay, siRNA transfection, enzyme-linked immunosorbent assay, quantitative reverse transcription-polymerase chain reaction, western blot, immunofluorescence, and cell ultrastructure analyses were conducted to investigate the mitigation of hypoxia-induced damage to SCs in vitro, revealing the effects of Mel on oxidative stress injury in SCs. Results: The overexpression of HIF-1 alpha in CoCl2-induced SCs (p < 0.05) indicated the establishment of an SCs hypoxia model. The proliferation and regeneration process of the hypoxic SCs enhanced in the Mel-treated group compared to the CoCl2 group has been proven through the CCK-8 experiment (p < 0.0001) and S-100 mRNA expression detection (p < 0.0001). The increased level of reactive oxygen species (ROS) (p < 0.001) and decreased superoxide dismutase (SOD) levels (p < 0.05) in the CoCl2-induced SCs indicated that Mel can alleviate the oxidative stress damage to SCs induced by CoCl2. Mel alleviated oxidative stress and inflammation in hypoxic SCs by reducing pro-inflammatory cytokines IL-1 beta (p < 0.0001) and TNF-alpha (p < 0.0001). In addition, Mel augmented cellular vitality and regulated indicators related to oxygen metabolism, cell repair, neurometabolism, and vascular endothelial formation after hypoxia, such as C-JUN (p < 0.05), glial cell line-derived neurotrophic factor (GDNF; p < 0.001), vascular endothelial growth factor (VEGF; p < 0.05), hypoxia-inducible factor 1-alpha (HIF-1 alpha; p < 0.05), interleukin-1 receptor type 1 (IL-1R1; p < 0.05), enolase1 (ENO1; p < 0.05), aldose reductase (AR; p < 0.01), SOD (p < 0.05), nerve growth factor (NGF; p < 0.05), and inducible nitric oxide synthase (iNOS; p < 0.05). In terms of its mechanism, Mel inhibited the expression of proteins associated with the NF-kappa B pathway such as IKK (p < 0.01), p65 (p < 0.05), p60 (p < 0.001), IRAK1 (p < 0.05), and increased IKB-alpha (p < 0.0001). Moreover, knocking out of IL-1R1 in the si-IL-1R1 group enhanced the therapeutic effect of Mel compared to the Mel-treated group (all of which p < 0.05). Conclusion: This research provided evidence of the substantial involvement of IL-1R1 in oxidative stress damage caused by hypoxia in SCs and proved that Mel alleviated oxidative stress injury in SCs by targeting IL-1R1 to downregulate the NF-kappa B-mediated inflammatory response. Mel could potentially serve as an innovative therapeutic approach for the treatment of IFP.

Abstract The aim of this study was to explore plant-derived peptides as carrier material with the function of anti-hot-melt stickiness of traditional Chinese herbal extracts during spray drying. Crataegi fructus extract (CFE) with a severe hot-melt stickiness problem was used as a model drug, and soy peptides (SPT) were screened as the most effective and suitable carrier material among seven plant-derived proteins and peptides which include soy protein isolate, walnut protein and five kinds of peptides (corn peptides, wheat peptides, walnut peptides, rice peptides and SPT). The addition of 15% SPT also exhibited a strong anti-stickiness effect in other four hot-melt sticky herbal extracts from Chinese herbs (Lycii fructus, Corni fructus, Chaenomelis fructus and Mume fructus) since the obtained powder increased from completely sticking to the wall to more than 50% powder yield. The dynamic surface tensions (DST) of CFE decreased consistently with the increase of SPT from 5% to 20%, and DST1000ms had consistent reduction with the addition of SPT from zero to 20%. Meanwhile, the adhesive force of the single droplet at 28 min decreased below 18.5 N. The softening point of the spray-dried powder of CFE added 15% SPT increased by about 40 °C, and the addition of 15% SPT improved the stability which might be similar with the addition of 50% MD based on scanning electron microscope analysis but more efficiently. These findings confirmed that SPT plant-derived could serve as effective and stable carrier material with good anti-stickiness ability during spray drying.

目的:建立一种同时测定康儿灵颗粒中新橙皮苷二氢查耳酮(NHDC)和纽甜含量的高效液相色谱(HPLC)分析方法.方法:采用Agilent Zorbax SB-Aq(4.6 mm×250 mm)色谱柱进行分离检测,以乙腈-水(21∶79)为流动相,流速为1 mL/min,检测波长为218 nm,柱温为30 ℃.结果:NHDC 和纽甜分别在1.89～189.00 μg/mL 和4.86～485.60 μg/mL范围内线性关系良好(r=0.999 9),平均加样回收率分别为97.59％、98.01％,RSD＜3.00％.结论:该方法重复性好、准确性高、操作简便,可用于食品、医药行业中NHDC 和纽甜的质量控制.

The high performance liquid chromatography(HPLC) characteristic chromatogram of Xiaoer Ganmaoning Oral Liquid(oral liquid for short) was established. The medicinal materials corresponding to characteristic peaks, their index components and ranges of similarity with the reference chromatograms were clarified. The similarity between the characteristic chromatograms of 10 batches of the oral liquid and the reference chromatogram was higher than 0.994. Eighteen characteristic peaks were identified, which were derived from different medicinal materials including Scutellariae Radix, Arctii Fructus, Lonicerae Japonicae Flos, Gardeniae Fructus and Forsythiae Fructus. Further, 11 characteristic peaks were assigned by the comparison with reference substances as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, isochlorogenic acid A, isochlorogenic acid C, baicalin, baicalein, wogonin, scutellarin, forsythiaside A and arctiin. Also, the characteristic chromatogram of precipitate in the oral liquid was established, and the similarity between characteristic chromatograms of 10 batches of the precipitate and the reference chromatogram was higher than 0.940. The 14 characteristic peaks originating from the precipitate and those from the oral liquid were consistent in retention time, and the content of all index components in the precipitate was lower than 5% of that in the oral liquid. Moreover, the stability of precipitate during the accelerated stability test was explored with filtration and Matlab-based image sensory evaluation. The precipitate mass and precipitation degree both increased over the stability test duration significantly. The stability of the oral liquid was used as a model system in this study to establish the integrated quality control system which related to medicinal materials, preparations and precipitate with HPLC characteristic chromatograms and image sensory evaluation, which lays a foundation for the exploration of the quantity value transfer of the oral liquid.

The traditional Chinese herb, Moschus (also called She Xiang in Chinese), is used to accelerate the rehabilitation of Bell’s palsy (BP) through acupoint sticking therapy in China. However, the mechanism of its effect is not clear. In this study, we explored the pharmacological mechanism using bioinformatics analysis. We identified 59 active ingredients in Moschus using the Traditional Chinese Medicine Integrated Database, including 17-beta-estradiol, testosterone, and 2,6-decamethylene pyridine. In total, 837 differently expressed genes were identified in blood of BP patients by RNA sequencing. Finally, 33 proteins were identified with overlapping predictions by the Comparative Toxicogenomics Database and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine. Proteins of interest were closely associated with 406 Gene Ontology biological processes and 4 pathways. The hub proteins in the protein–protein interaction network were FOS, JUN, proopiomelanocortin, and G protein-coupled estrogen receptor 1. A pharmacology network was constructed with 15 active components of Moschus, 33 protein targets and four pathways. The docking model of androst-4-ene-3,17-dione and FOS-JUN complexes was predicted and constructed. The results indicated testosterone as an effective component of Moschus that may enhance BP rehabilitation by targeting FUN and the mitogen-activated protein kinase and cyclic adenosine monophosphate signaling pathways, and that docking of androst-4-ene-3,17-dione and FOS-JUN complexes might play a critical role. The findings provide a direction for future research to verify the key targets of Moschus in the treatment of BP and an application prospect in the field of facial nerve rehabilitation.

High shear wet granulation (HSWG), as a widely used granulation technology, has been studied extensively. However, for the HSWG of formulations containing hydrophobic components, the influence of process variables on the properties of granules and tablets has not been reported. In the present study, based on a combination of quality by design and multivariate analysis (MVA) approaches, quercetin with high-dose and high-hydrophobicity was used to study the relationship between process variables, granule properties, and tablet properties in HSWG systematically. Control and response variables were determined using risk assessment. The optimal fitting empirical models established by Box-Behnken design showed that the liquid to solid ratio and impeller speed were the most important factors, which affected all product properties except Carr's index and yield pressure. Instead, the influence of wet massing time was relatively small (only the effects on yield, granule size, granule hardness, and compression ratio were significant). Then, the process design space was obtained by limiting the related critical quality attributes, which was verified effectively. Scanning electron microscope images showed that smooth granules were produced using higher process parameters, whereas rough and porous granules resulted at lower process parameters. Furthermore, the MVA results demonstrated that increasing the granule hardness led to an increase in the compression ratio and a decrease in tensile strength of the tablets. Tablet fragility and disintegration time were mainly affected by granule density and bulk density, respectively, and both were negatively correlated. The established research paradigm is not only conducive to the successful development of quercetin products, but also provides valuable guidance for improving HSWG-based product development with such formulation characteristics. (C) 2021 The Society of Powder Technology Japan. Published by Elsevier BV and The Society of Powder Technology Japan. All rights reserved.

As insoluble polymer materials, ion-exchange resins (IERs) can exchange their own ions with desirable charged ions in the solution. According to the affinity of active moieties for soluble counterions, IERs could be categorized into the following four types: strongly acidic cation, weakly acidic cation, strongly basic anion, and weakly basic anion exchange resins. Due to their relative safety and high drug-loading capacity, IERs have garnered extensive attention in the pharmaceutical field since the 1950s. As numerous investigations combine drugs with IERs, this article summarizes the technologies employed in these studies from four aspects: IER screening principles, combining technologies, characterization methods, and in vitro and in vivo release of drug-resinate complexes. In addition, the advantages and disadvantages of various technologies and their scope are expounded. The article provides new insights on the preparation of ion-exchange resin complexes.

目的:探究基质用量与涂布前膏体质构特征物理性质(特征物理性质)、贴膏涂布性能之间的相关性.方法:以贴膏成型质量和涂布性能为指标,选取部分中和的聚丙烯酸钠(NP700)、甘羟铝等6个重要辅料基质进行处方设计,每种基质用量设定为5个水平,共计30首处方.采用物性测定仪对30首不同处方、7个不同时间点的210个涂布前膏体样品的涂抹性、硬度、黏弹性等特征物理性质参数进行测定,运用相关性分析、主成分分析等方法对数据进行处理.结果:随基质NP700、聚维酮K30、酒石酸用量及油相比例的增大,涂布前膏体的涂抹性、硬度、稠度、提拉强度、内聚力、变化速率及黏弹性特征物理性质参数均相应增大,适宜的涂布时间缩短,容易出现皱布现象.在对样品特征物理性质参数进行主成分分析后,210个样品可明显分为可涂布和不可涂布样品两大类.结论:通过减少基质NP700、聚维酮K30、酒石酸用量及油相比例,可降低涂布前膏体涂抹性、硬度、稠度、内聚力等特征物理性质参数,从而对贴膏的涂布性能进行优化.

Arthritis is a general term for various types of inflammatory joint diseases. The most common clinical conditions are mainly represented by rheumatoid arthritis and osteoarthritis, which affect more than 4% of people worldwide and seriously limit their mobility. Arthritis medication generally requires long-term application, while conventional administrations by oral delivery or injections may cause gastrointestinal side effects and are inconvenient for patients during long-term application. Emerging microneedle (MN) technology in recent years has created new avenues of transdermal delivery for arthritis drugs due to its advantages of painless skin perforation and efficient local delivery. This review summarizes various types of arthritis and current therapeutic agents. The current development of MNs in the delivery of arthritis drugs is highlighted, demonstrating their capabilities in achieving different drug release profiles through different self-enhancement methods or the incorporation of nanocarriers. Furthermore, the challenges of translating MNs from laboratory studies to the clinical practice and the marketplace are discussed. This promising technology provides a new approach to the current drug delivery paradigm in treating arthritis in transdermal delivery.

目的:开发中药流化床制粒颗粒生长过程预测模型,将中药制剂处方工艺研发由传统实验室试错法向科学化、数字化与智能化转变.方法:采用SolidWorks Premium软件构建流化床顶喷制粒机基本工况,采用ANSYS ICEM CFD软件划分工况网格.采用计算流体力学(computational fluid dynamics,CFD)构建颗粒成型数学模型,自定义颗粒成型机制规则并将其编制成用户自定义函数.将所构建的CFD模型分别用于金钱草提取物和垂盆草提取物流化床制粒工艺数值模拟研究,同时进行流化床制粒实验验证,对比数值模拟与实验结果的一致性.结果:模拟结果显示,金钱草提取物颗粒和垂盆草提取物颗粒的粒径均随模拟时间延长而增大,且粒径分布逐渐变宽.床层内颗粒的速度、颗粒与流体混合相的压力因颗粒粒径的不断变化而发生相应变化.颗粒粒径增长速率及颗粒空间分布状态的实验结果与数值模拟结果均具有较好的一致性.结论:对中药流化床制粒颗粒增长趋势的模拟可用于预测或判断处方工艺的适宜性,从而对最终颗粒的关键质量属性进行有效控制.

制备具有掩味效果的盐酸小檗碱树脂复合物.以盐酸小檗碱为模型药物,Amberlite IRP69为载药树脂,通过阐明一定温度范围内盐酸小檗碱在潜溶剂中的溶解度与温度关系曲线,指导复合物制备过程中盐酸小檗碱的加入量及反应温度等参数的研究.对制得的复合物进行物性表征和体外释放研究,验证复合物的形成并预测复合物的体内释放行为.实验结果表明,用60％乙醇作为潜溶剂在50℃下恒温搅拌1h,制得的复合物载药量和药物利用率分别为35％和64％,且具有较好的掩味效果.本研究提供了一种制备盐酸小檗碱掩味制剂的方法.

本文通过研究粒子修饰技术改善中药生粉类药材的流动性和压缩成型性,为满足下一步制剂制备的需求.以金银花粉末作为模型药物,采用流化床底喷技术,使用共聚维酮作为修饰剂,制备修饰粒子;分别测定各粉体的粉体学性质、片剂压缩成型参数以及崩解时限和溶出度,并结合扫描电镜技术对修饰前后粉体粒子和压制的片剂表面形态进行表征.结果 表明,经过粒子修饰后,金银花粉体粒子粒径增大,其粉体的流动性、可压缩性以及成型性均得到一定的改善,并且其崩解时限也有一定的降低,体外溶出度也不受影响.因此,本研究可以为中药生粉类药材因流动性、可压性等粉体属性较差而不能满足制剂生产需要这一共性问题提供参考和思路.