International Journal of Pharmaceutics: X最新文献_第2页

Preparation of atorvastatin calcium-loaded liposomes using thin-film hydration and coaxial micromixing methods: A comparative study 薄膜水化与同轴微混合法制备阿托伐他汀载钙脂质体的比较研究。

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2024-12-01 DOI: 10.1016/j.ijpx.2024.100309

Faezeh Dangkoub , Mehri Bemani Naeini , Shima Akar , Ali Badiee , Mahmoud Reza Jaafari , Mojtaba Sankian , Mohsen Tafaghodi , Seyed Ali Mousavi Shaegh

Development of techniques to produce nanoformulations in a controlled and reproducible manner is of great importance for research, clinical trials, and industrial scale-up. This research aimed to introduce a cost-effective micromixing approach for the nanoassembly of liposomes and compared with thin-film hydration (TFH) method. Numerical simulations and design of experiments (DOE) by response surface methodology (RSM) were used to evaluate the effects of input parameters on liposome properties, aiming to identify optimal conditions. Anionic liposomes without or with atorvastatin calcium (ATC) produced using TFH and the micromixing methods showed similar characteristics in size (150–190 nm), PDI (<0.2), and zeta potential (−50 to −60 mV). Both methods achieved about 70 % encapsulation efficiency with similar drug release profile for ATC-containing liposomes. Analysis of stability and DSC thermograms revealed comparable outcomes for liposomes prepared using both techniques. Nanoliposomes produced via both approaches indicated similar in vitro biological performance regarding cellular uptake and cell viability. The micromixing approach presented an alternative method to produce nanoliposomes in a one-step manner with high controllability and reproducibility without requiring specialized equipment. Compatibility of the micromixer with various solvents, including those detrimental to conventional microfluidic materials like PDMS and thermoplastics, enables exploration of a wide range of formulations.

开发以可控和可重复的方式生产纳米制剂的技术对研究、临床试验和工业规模扩大具有重要意义。本研究旨在介绍一种具有成本效益的微混合方法用于脂质体的纳米组装，并与薄膜水化（TFH）方法进行比较。采用响应面法（RSM）进行数值模拟和实验设计（DOE），评估输入参数对脂质体性质的影响，以确定最佳条件。不含或含阿托伐他汀钙（ATC）的阴离子脂质体采用TFH法和微混合法制备，其大小（150 ~ 190 nm）、PDI (

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引用次数: 0

Improved topical delivery of curcumin by hydrogels formed by composite carriers integrated with cyclodextrin metal-organic frameworks and cyclodextrin nanosponges 由环糊精金属有机框架和环糊精纳米海绵组成的复合载体形成的水凝胶改善了姜黄素的局部递送。

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2024-12-01 DOI: 10.1016/j.ijpx.2024.100310

Songting Li , Meng Long , Jiaqi Li , Yongtai Zhang , Nianping Feng , Zhicheng Zhang

Curcumin (CUR) is highly promising for topical therapeutic applications, but water-insolubility is one of the major challenges plaguing its drugability, while conventional lipid nanocarriers are limited by low drug-carrying capacity, many additives, and complex processes. In the current work, we constructed a composite carrier integrated with cyclodextrin metal-organic framework (γ-CD-MOF) and cyclodextrin nanosponge (β-CDNS), in which the γ-CD-MOF had 13.9 % drug loading and 267.1-fold increase in solubility in water for CUR, and the β-CDNS showed bioadhesion and further increasing drug solubility. The composite carrier (γ-CD-MOF@β-CDNS) significantly improved the in vitro release and transdermal permeation of CUR, and its limited water absorption properties and excellent bioadhesion create an advantage in the local administration of the drug for treating diseases with high exudate, which prevents the affected area from deteriorating the condition by counter-absorption of water from the formulation. Thus, this composite carrier contributes a new option to address the local delivery of insoluble drugs and offers a promising strategy for the clinical application of CUR.

姜黄素（Curcumin， CUR）在局部治疗方面具有很高的应用前景，但水不溶性是影响其药性的主要挑战之一，而传统的脂质纳米载体受载药量低、添加剂多和工艺复杂的限制。本研究构建了环糊精金属有机骨架（γ-CD-MOF）和环糊精纳米海绵（β-CDNS）复合载体，其中γ-CD-MOF的载药量为13.9%，水溶性提高267.1倍，且β-CDNS具有生物黏附性，进一步提高了药物的溶解度。复合载体（γ-CD-MOF@β-CDNS）显著改善了CUR的体外释放和透皮渗透，其有限的吸水性能和优异的生物粘附性为局部给药治疗高渗出性疾病创造了优势，可防止患处因配方中的水分反吸收而恶化病情。因此，这种复合载体为解决不溶性药物的局部递送提供了新的选择，并为CUR的临床应用提供了一个有希望的策略。

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引用次数: 0

Disulfiram and cancer immunotherapy: Advanced nano-delivery systems and potential therapeutic strategies 双硫仑和癌症免疫疗法：先进的纳米给药系统和潜在的治疗策略

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2024-11-22 DOI: 10.1016/j.ijpx.2024.100307

Di Huang , Yinsha Yao , Yifei Lou , Longfa Kou , Qing Yao , Ruijie Chen

The initial focus of the clinical application of disulfiram was its efficacy in treating alcoholism. However, recent research has revealed its potential as an anti-tumor agent and even as an enhancer of cancer immunotherapy. Disulfiram has received safety approval from the FDA, indicating its safety advantages over other substances used for disease treatment. Although clinical trials have been conducted on strategies involving disulfiram or its combination with other anti-tumor drugs, the treatment outcomes have not yielded satisfactory results, thereby emphasizing the significance of addressing drug delivery as a crucial challenge to be resolved. The need to explore advanced nano-delivery systems and the potential immunotherapy enhancement effect of disulfiram in cancer treatment has increased. This review highlights various ways in which disulfiram can combat cancer and importantly, activate immune-related mechanisms. It also discusses obstacles related to delivering disulfiram and provides existing solutions in terms of drug delivery. These drug delivery strategies offer solutions to address various challenges encountered in diverse delivery methods and aim to achieve enhanced therapeutic effects. The focus is on recent advancements in disulfiram delivery strategies and the future potential of disulfiram in immune regulation.

双硫仑临床应用的最初重点是其治疗酒精中毒的功效。不过，最近的研究发现，它具有抗肿瘤剂甚至是癌症免疫疗法增强剂的潜力。双硫仑已获得美国食品及药物管理局的安全认证，这表明它比其他用于疾病治疗的物质更安全。虽然已经开展了涉及双硫仑或其与其他抗肿瘤药物组合的临床试验，但治疗结果并不令人满意，因此强调了解决药物递送这一关键挑战的重要性。探索先进的纳米给药系统以及双硫仑在癌症治疗中潜在的免疫疗法增强效果的需求日益增加。本综述重点介绍了双硫仑抗击癌症的各种方法，尤其是激活免疫相关机制的方法。综述还讨论了与双硫仑给药相关的障碍，并提供了现有的给药解决方案。这些给药策略为解决不同给药方法中遇到的各种难题提供了解决方案，旨在实现更强的治疗效果。重点是双硫仑给药策略的最新进展以及双硫仑在免疫调节方面的未来潜力。

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引用次数: 0

Prodigiosin hydrogel to promote healing of trauma-infected multidrug-resistant Staphylococcus aureus mice wounds 促进创伤感染的耐多药金黄色葡萄球菌小鼠伤口愈合的原薯蓣皂苷水凝胶

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2024-11-21 DOI: 10.1016/j.ijpx.2024.100306

Xin Wang, Guangfan Meng, Zongyu Zhang, Jiacheng Zhao, Shaoyu Wang, Dongliang Hua, JingZhang, Jie Zhang

Wound infections caused by Multidrug-resistant Staphylococcus aureus (MRSA) have been regarded as a challenging problem in clinic for the long time. In this study, based on the excellent antimicrobial effect of prodigiosin(PG) and the ability of hydrogel dressing in terms of tissue repair and regeneration, we prepared the PG hydrogel as a treatment for the wound infection induced by MRSA. Rheological tests indicated that PG hydrogel as a semi-solid gel had good mechanical properties. In ex vitro drug permeation studies and dermatokinetic studies showed that PG hydrogel had high PG permeability and were capable of short-term retention in the skin. In addition, in vivo experiments for mouse skin wounds showed that the serum levels of inflammatory factors including IL-β and other inflammatory factors were reduced, the inflammatory infiltration of tissues was reduced, the transcript levels of genes such as COL1A1 were up-regulated at different stages of wound healing, and the relative abundance of genera such as Desulfovibrio was lowered after treatment with PG hydrogel, which facilitated wound healing in mice. Our study would provide a new solution to the clinical shortage of drugs for the treatment of MRSA infection and provide a research basis for improving the comprehensive values of PG.

长期以来，耐多药金黄色葡萄球菌（MRSA）引起的伤口感染一直被视为临床上的难题。本研究基于原肌苷（PG）卓越的抗菌效果和水凝胶敷料在组织修复和再生方面的能力，制备了 PG 水凝胶，用于治疗 MRSA 引起的伤口感染。流变学测试表明，PG 水凝胶作为一种半固体凝胶具有良好的机械性能。体外药物渗透研究和皮肤动力学研究表明，PG 水凝胶具有较高的 PG 渗透性，并能在皮肤中短期滞留。此外，对小鼠皮肤伤口的体内实验表明，使用 PG 水凝胶处理后，小鼠血清中的 IL-β 等炎症因子水平降低，组织的炎症浸润减少，COL1A1 等基因的转录水平在伤口愈合的不同阶段上调，脱硫弧菌等菌属的相对丰度降低，从而促进了小鼠伤口的愈合。我们的研究将为临床上治疗 MRSA 感染的药物短缺提供新的解决方案，并为提高 PG 的综合价值提供研究基础。

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引用次数: 0

Trastuzumab-functionalized SK-BR-3 cell membrane-wrapped mesoporous silica nanoparticles loaded with pyrotinib for the targeted therapy of HER-2-positive breast cancer 负载有吡罗替尼的曲妥珠单抗功能化 SK-BR-3 细胞膜包裹介孔二氧化硅纳米粒子用于 HER-2 阳性乳腺癌的靶向治疗

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2024-11-14 DOI: 10.1016/j.ijpx.2024.100302

Xing Liu, Wenwen Shen

In this study, the trastuzumab-functionalized SK-BR-3 cell membrane-wrapped mesoporous silica nanoparticles loaded with pyrotinib (Tra-CM-MSN-PYR) were prepared for targeted therapy of HER2-positive breast cancer. Transmission electron microscopy (TEM) characterization showed that MSN had a spherical morphology with mesoporous channels and that the structure of Tra-CM-MSN was a cell membrane (CM) layer successfully coated on the surface of MSN. A cellular uptake assay demonstrated that FITC-labeled Tra-CM-MSN were taken up by SK-BR-3 breast cancer cells, which illustrated that Tra-CM-MSN had good targeting ability compared with CM-MSN and MSN. In vivo imaging experiments demonstrated significant accumulation of FITC-labeled Tra-CM-MSN in tumor tissues, further proving that Tra-CM-MSN have superior targeting properties. Cell apoptosis experiments suggested that Tra-CM-MSN-PYR significantly inhibited the proliferation of SK-BR-3 breast cancer cells. The results of in vivo animal experiments also showed that Tra-CM-MSN-PYR significantly inhibited tumor growth. These results indicate that Tra-CM-MSN-PYR has potential application as a targeted therapy for HER2-positive breast cancer in the future.

本研究制备了负载吡罗替尼的曲妥珠单抗功能化SK-BR-3细胞膜包裹介孔二氧化硅纳米颗粒（Tra-CM-MSN-PYR），用于HER2阳性乳腺癌的靶向治疗。透射电子显微镜（TEM）表征显示，MSN具有球形形态和介孔通道，Tra-CM-MSN的结构是成功包覆在MSN表面的细胞膜（CM）层。细胞摄取实验表明，FITC标记的Tra-CM-MSN能被SK-BR-3乳腺癌细胞摄取，这说明Tra-CM-MSN与CM-MSN和MSN相比具有良好的靶向能力。体内成像实验表明，FITC 标记的 Tra-CM-MSN 在肿瘤组织中有显著积累，进一步证明了 Tra-CM-MSN 具有卓越的靶向特性。细胞凋亡实验表明，Tra-CM-MSN-PYR 能明显抑制 SK-BR-3 乳腺癌细胞的增殖。体内动物实验结果也表明，Tra-CM-MSN-PYR 能明显抑制肿瘤生长。这些结果表明，Tra-CM-MSN-PYR 未来有可能用作 HER2 阳性乳腺癌的靶向疗法。

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引用次数: 0

Kinetics of elastic recovery in roll compaction 碾压过程中的弹性恢复动力学

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2024-11-14 DOI: 10.1016/j.ijpx.2024.100303

Martin Lück, Stefan Klinken-Uth, Peter Kleinebudde

Elastic recovery (

ER

) has been investigated and discussed extensively in the field of tableting. However, until now only limited data is available regarding

ER

in roll compaction. Therefore, a previously established in-line measurement technique was rolled out to further investigate the kinetics of

ER

in roll compaction and the effects of specific compaction force (

SCF

) and roll speed (

RS

). In-line laser triangulation measurements at different positions within a roll rotation as well as measurement over time after the process has been stopped were utilized. Pure microcrystalline cellulose (

MCC

) and two placebo powder blend formulations were analysed. Successful fit of the contained

ER

profiles emphasized that the

ER

on the roll surface is build out of two exponential kinetics. Starting with a dominating fast

ER

(

{ER}_{A}

), characterized by a high increase of the ribbon thickness after passing the gap width, followed by a slower

ER

(

{ER}_{B}

). Sigma minus plot analysis showed that increasing

RS

led to an accelerated

{ER}_{A}

and

{ER}_{B}

which was related to the viscoelastic behaviour of

MCC

. The

SCF

only had an effect on the kinetics of

ER

if a brittle filler was added to the mixture. The conducted study established the first approach in literature to characterize the kinetics of

ER

in roll compaction. It supports the understanding and characterization of relaxation times and the effect of the

RS

and

SCF

in roll compaction.

弹性恢复（ER）在压片领域得到了广泛的研究和讨论。然而，到目前为止，有关辊式压实中ER的数据还很有限。因此，为了进一步研究辊式压实中的ER动力学以及特定压实力（SCF）和辊速（RS）的影响，我们采用了先前建立的在线测量技术。在轧辊旋转的不同位置进行了在线激光三角测量，并在工艺停止后进行了随时间变化的测量。对纯微晶纤维素（MCC）和两种安慰剂粉末混合配方进行了分析。所含ER曲线的成功拟合强调了轧辊表面的ER是由两个指数动力学组成的。首先是快速ER（ERA），其特点是通过间隙宽度后，辊带厚度增加较快，然后是慢速ER（ERB）。西格玛负值图分析表明，增加 RS 会导致加速ERA 和 ERB，这与 MCC 的粘弹性有关。只有在混合物中加入脆性填料时，SCF 才会对 ER 动力学产生影响。这项研究首次在文献中确定了辊式压实中ER的动力学特征。它有助于理解和表征辊式压实中的松弛时间以及 RS 和 SCF 的影响。

{"title":"Kinetics of elastic recovery in roll compaction","authors":"Martin Lück, Stefan Klinken-Uth, Peter Kleinebudde","doi":"10.1016/j.ijpx.2024.100303","DOIUrl":"10.1016/j.ijpx.2024.100303","url":null,"abstract":"<div><div>Elastic recovery (<span><math><mi>ER</mi></math></span>) has been investigated and discussed extensively in the field of tableting. However, until now only limited data is available regarding <span><math><mi>ER</mi></math></span> in roll compaction. Therefore, a previously established in-line measurement technique was rolled out to further investigate the kinetics of <span><math><mi>ER</mi></math></span> in roll compaction and the effects of specific compaction force (<span><math><mi>SCF</mi></math></span>) and roll speed (<span><math><mi>RS</mi></math></span>). In-line laser triangulation measurements at different positions within a roll rotation as well as measurement over time after the process has been stopped were utilized. Pure microcrystalline cellulose (<span><math><mi>MCC</mi></math></span>) and two placebo powder blend formulations were analysed. Successful fit of the contained <span><math><mi>ER</mi></math></span> profiles emphasized that the <span><math><mi>ER</mi></math></span> on the roll surface is build out of two exponential kinetics. Starting with a dominating fast <span><math><mi>ER</mi></math></span> (<span><math><msub><mi>ER</mi><mi>A</mi></msub></math></span>), characterized by a high increase of the ribbon thickness after passing the gap width, followed by a slower <span><math><mi>ER</mi></math></span> (<span><math><msub><mi>ER</mi><mi>B</mi></msub></math></span>). Sigma minus plot analysis showed that increasing <span><math><mi>RS</mi></math></span> led to an accelerated <span><math><msub><mi>ER</mi><mi>A</mi></msub></math></span> and <span><math><msub><mi>ER</mi><mi>B</mi></msub></math></span> which was related to the viscoelastic behaviour of <span><math><mi>MCC</mi></math></span>. The <span><math><mi>SCF</mi></math></span> only had an effect on the kinetics of <span><math><mi>ER</mi></math></span> if a brittle filler was added to the mixture. The conducted study established the first approach in literature to characterize the kinetics of <span><math><mi>ER</mi></math></span> in roll compaction. It supports the understanding and characterization of relaxation times and the effect of the <span><math><mi>RS</mi></math></span> and <span><math><mi>SCF</mi></math></span> in roll compaction.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100303"},"PeriodicalIF":5.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142701186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanistic insights of desmopressin loaded elastic liposomes for transdermal delivery: HSPiP predictive parameters and instrumental based evidences 去氨加压素弹性脂质体透皮给药的机理研究：HSPiP 预测参数和基于仪器的证据

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2024-11-13 DOI: 10.1016/j.ijpx.2024.100304

Afzal Hussain , Mohammad A. Altamimi , Musaad A. Alshammari

Desmopressin acetate (DA) is a first-line option for the treatment of hemophilia A, von Willebrand's disease, nocturnal enuresis, central diabetes insipidus, and various traumatic injuries. We extended previously reported desmopressin-loaded elastic liposomes (ODEL1) to investigate mechanistic insights into ODEL1 mediated augmented permeation across rat skin. HSPiP software and instrumental techniques such as differential scanning calorimeter (DSC), Fourier Transform infrared (FTIR), scanning electron microscopy (SEM), and fluorescent microscopy provided better understandings of permeation behavior. HSPiP was used to compare Hansen solubility parameter (HSP) of ODEL1, DA, components, and rat skins (control and treated) in terms of dispersion forces (δ_d), polar forces (δ_p), and hydrogen bonding (δ_h). FTIR, DSC, fluorescence microscopy, and SEM provided a detailed mechanistic understanding of the changes occurred after treatment. The values of δ_d, δ_p, and δ_H for DA were 20.6, 31.9, and 18.2 MPa^1/2, respectively, whereas these were 15.6, 14.97, and 2.4 MPa^1/2 for ODEL1, respectively, suggesting remarkable permeation of DA by changing innate cohesive energies of the skin. DA primarily interacts through δ_d and δ_p with the ODEL1 and the skin. Furthermore, the stretching and bending vibrations (molecular interactions) of the treated skins were quite diverse as compared to the untreated skin. ODEL1 caused a substantial thermal changes (shifted 67 to 65 °C, and 79 to 82.5 °C) for the surface protein and glycoprotein as compared to the untreated skin. Fluorescence and SEM confirmed relatively intense surface perturbation of the treated skin as compared to the control. Thus, ODEL1 was efficient in interacting with the skin surface for reversible changes and subsequently resulted in high permeation and drug deposition.

醋酸去氨加压素（DA）是治疗 A 型血友病、冯-威廉氏病、夜间遗尿症、中枢性糖尿病和各种创伤的一线药物。我们扩展了之前报道的去氨加压素负载弹性脂质体（ODEL1），研究了 ODEL1 介导的大鼠皮肤渗透增强的机理。HSPiP 软件以及差示扫描量热仪 (DSC)、傅立叶变换红外光谱 (FTIR)、扫描电子显微镜 (SEM) 和荧光显微镜等仪器技术有助于更好地了解渗透行为。HSPiP 用于从分散力（δd）、极性力（δp）和氢键（δh）方面比较 ODEL1、DA、组分和大鼠皮（对照组和处理组）的汉森溶解度参数（HSP）。傅立叶变换红外光谱（FTIR）、DSC、荧光显微镜和扫描电子显微镜从机理上详细了解了处理后发生的变化。DA 的 δd、δp 和 δH 值分别为 20.6、31.9 和 18.2 MPa1/2，而 ODEL1 分别为 15.6、14.97 和 2.4 MPa1/2，这表明 DA 通过改变皮肤的先天内聚能而显著渗透。DA 主要通过 δd 和 δp 与 ODEL1 和皮肤相互作用。此外，与未处理的皮肤相比，处理过的皮肤的拉伸和弯曲振动（分子相互作用）差异很大。与未经处理的皮肤相比，ODEL1 使表面蛋白质和糖蛋白发生了显著的热变化（温度分别从 67 °C升至 65 °C，从 79 °C升至 82.5 °C）。荧光和扫描电子显微镜证实，与对照组相比，处理过的皮肤表面发生了相对强烈的扰动。因此，ODEL1 能有效地与皮肤表面相互作用，使其发生可逆变化，从而实现高渗透性和药物沉积。

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引用次数: 0

Olive mill wastewater: From by-product to smart antioxidant material 橄榄油厂废水：从副产品到智能抗氧化材料

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2024-11-07 DOI: 10.1016/j.ijpx.2024.100301

Marco Ruggeri , Fabrizio De Luca , Amedeo Ungolo , Barbara Vigani , Alejandro J. Paredes , Eleonora Russo , Maria Grazia Bottone , Eleonora Bianchi , Franca Ferrari , Silvia Rossi , Giuseppina Sandri

Olive mill wastewater (OMWW) is a byproduct of olive oil extraction that represents a critical environmental concern due to its potential adverse effects on ecosystems. Given these premises, spray-dried microparticles were designed and developed using maltodextrins as carriers to encapsulate OMWW bioactive compounds. The microparticles were manufactured using an easily scalable and sustainable spray-drying process. The resulting microparticles were smooth, spherical, and exhibited a mean particle size of about 18 μm. The systems demonstrated notable antioxidant properties with a DPPH radical scavenging activity higher than 60 %, due to the polyphenolic compounds of OMWW (about 24 g gallic acid equivalents per g of sample). In addition, the microparticles supported fibroblast and macrophage viability at concentrations up to 1 mg/mL. They also determined a 4-fold inflammation reduction in macrophages, improved collagen expression in fibroblasts, and modulated oxidative stress on aged fibroblasts. In conclusion, these microparticles could be considered as promising medical devices in wound healing, while offering a sustainable solution for valorizing OMWW.

橄榄榨油厂废水（OMWW）是橄榄油榨取过程中产生的一种副产品，由于其对生态系统可能产生的不利影响，它已成为一个重要的环境问题。有鉴于此，我们设计并开发了以麦芽糊精为载体的喷雾干燥微粒，用于封装 OMWW 生物活性化合物。微颗粒的制造采用了易于扩展且可持续的喷雾干燥工艺。制得的微颗粒光滑、呈球形，平均粒径约为 18 μm。由于 OMWW 中的多酚化合物（每克样品中约有 24 克没食子酸当量），该系统具有显著的抗氧化特性，其 DPPH 自由基清除活性高于 60%。此外，当浓度达到 1 毫克/毫升时，微颗粒还能支持成纤维细胞和巨噬细胞的活力。他们还发现巨噬细胞中的炎症减少了 4 倍，成纤维细胞中胶原蛋白的表达得到改善，老化成纤维细胞的氧化应激得到调节。总之，这些微粒可被视为伤口愈合方面很有前景的医疗设备，同时也为实现 OMWW 价值化提供了一种可持续的解决方案。

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引用次数: 0

Ultrasound-targeted sirolimus-loaded microbubbles improves acute rejection of heart transplantation in rats by inhibiting TGF-β1-Smad signaling pathway, promoting autophagy and reducing inflammation 超声靶向西罗莫司负载微气泡通过抑制 TGF-β1-Smad 信号通路、促进自噬和减轻炎症，改善大鼠心脏移植的急性排斥反应

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2024-11-04 DOI: 10.1016/j.ijpx.2024.100300

Haiwei Bao, Lulu Dai, Huiyang Wang, Tianan Jiang

Acute rejection (AR) remains a pivotal complication and leading cause of mortality within the first year following heart transplantation (HT). In this study, we assessed the impact of ultrasound-targeted microbubbles loaded with sirolimus (SIR-MBs) on AR in a rat HT model and delved into the underlying mechanisms. We established a rat abdominal ectopic HT model, which was stratified into three groups receiveing the PBS, SIR-MBs + ultrasound-targeted microbubble destruction (UTMD), and sirolimus, respectively. The protective effects of each treatments on survival rate, inflammatory response, autophagy and TGF-β1-Smad signaling pathway-related proteins were evaluted. Additionally, rescue experiment was performed via adding the autophagy inhibitor or TGF-β1 agonist in combination therapy. UTMD combined SIR-MBs mediated 15-fold higher local drug concentration compared to direct sirolimus administration. The infiltration of inflammatory cells in the transplanted hearts indicated that SIR-MBs combined with UTMD were effective in mitigating the inflammatory response, achieving levels significantly lower than those observed in the sirolimus group. Furthermore, after SIR-MBs combined with UTMD treatment, the expression levels of TGF-β1-Smad signaling pathway-related proteins in heart tissues also showed a significant decrease compared to the model control group. Conversely, the expressions of autophagy proteins LC3-II, Beclin-1 and β-arrestin showed an up-regulated trend. Rescue experiments also revealed that the enhancement in survival trends was markedly suppressed following the administration of CsA or SRI-011381, respectively. Collectively, our findings suggest that SIR-MBs combined with UTMD augment the local treatment efficacy for AR in rat HT models by inhibiting the TGF-β1-Smad signaling pathway, promoting autophagy, and alleviating inflammation.

急性排斥反应（AR）仍然是心脏移植（HT）后第一年内的重要并发症和主要致死原因。在这项研究中，我们评估了装载西罗莫司的超声靶向微泡（SIR-MBs）对大鼠心脏移植模型中急性排斥反应的影响，并深入研究了其潜在机制。我们建立了大鼠腹部异位 HT 模型，并将其分为三组，分别接受 PBS、SIR-MBs + 超声靶向微泡破坏（UTMD）和西罗莫司治疗。评估各处理对存活率、炎症反应、自噬和 TGF-β1-Smad 信号通路相关蛋白的保护作用。此外，还通过在联合治疗中加入自噬抑制剂或 TGF-β1 激动剂进行了挽救实验。UTMD联合SIR-MBs介导的局部药物浓度比直接服用西罗莫司高15倍。移植心脏中炎症细胞的浸润情况表明，SIR-MBs 与 UTMD 联用能有效减轻炎症反应，其水平明显低于西罗莫司组。此外，SIR-MBs联合UTMD治疗后，心脏组织中TGF-β1-Smad信号通路相关蛋白的表达水平也比模型对照组显著下降。相反，自噬蛋白LC3-II、Beclin-1和β-arrestin的表达呈上升趋势。挽救实验还发现，分别给予 CsA 或 SRI-011381 后，存活趋势的增强被明显抑制。总之，我们的研究结果表明，SIR-MBs 与UTMD 联合使用可通过抑制 TGF-β1-Smad 信号通路、促进自噬和缓解炎症来增强大鼠 HT 模型中 AR 的局部疗效。

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引用次数: 0

A hybrid system of mixture models for the prediction of particle size and shape, density, and flowability of pharmaceutical powder blends 用于预测药粉混合物粒度和粒形、密度和流动性的混合模型系统

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2024-10-28 DOI: 10.1016/j.ijpx.2024.100298

Mohammad Salehian , Jonathan Moores , Jonathan Goldie , Isra' Ibrahim , Carlota Mendez Torrecillas , Ishwari Wale , Faisal Abbas , Natalie Maclean , John Robertson , Alastair Florence , Daniel Markl

This paper presents a system of hybrid models that combine both mechanistic and data-driven approaches to predict physical powder blend properties from their raw component properties. Mechanistic, probabilistic models were developed to predict the particle size and shape, represented by aspect ratio, distributions of pharmaceutical blends using those of the raw components. Additionally, the accuracy of existing mixture rules for predicting the blend's true density and bulk density was assessed. Two data-driven models were developed to estimate the mixture's tapped density and flowability (represented by the flow function coefficient, FFC) using data from 86 mixtures, which utilized the principal components of predicted particle size and shape distributions in combination with the true density, and bulk density as input data, saving time and material by removing the need for resource-intensive shear testing for raw components. A model-based uncertainty quantification technique was designed to analyse the precision of model-predicted FFCs. The proposed particle size and shape mixture models outperformed the existing approach (weighted average of distribution percentiles) in terms of prediction accuracy while providing insights into the full distribution of the mixture. The presented hybrid system of models accurately predicts the mixture properties of different formulations and components with often

R^{2} > 0.8

, utilising raw material properties to reduce time and material resources on preparing and characterising blends.

本文介绍了一套混合模型系统，该系统结合了机理和数据驱动方法，可根据原料成分的特性预测粉末混合物的物理特性。本文开发了机理概率模型，利用原料成分的粒度和粒形分布预测药物混合物的粒度和粒形（以长宽比表示）。此外，还对现有混合物规则预测混合物真实密度和体积密度的准确性进行了评估。利用来自 86 种混合物的数据，开发了两种数据驱动模型来估算混合物的挖掘密度和流动性（以流动功能系数 FFC 表示），该模型利用预测粒度和粒形分布的主成分以及真实密度和体积密度作为输入数据，无需对原料成分进行资源密集型剪切测试，从而节省了时间和材料。设计了一种基于模型的不确定性量化技术，用于分析模型预测的 FFC 的精度。所提出的粒度和粒形混合物模型在预测精度方面优于现有方法（分布百分位数加权平均），同时提供了对混合物全面分布的深入了解。所提出的混合模型系统能准确预测不同配方和成分的混合物特性，R2 通常为 0.8，利用原材料特性减少了制备和表征混合物所需的时间和材料资源。

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