European Journal of Pharmaceutics and Biopharmaceutics最新文献_第6页

The effect of recombinant VEGF and merwinite nanoparticles within a 3D-printed scaffold containing hyaluronic acid–fucoidan on craniofacial osteoangiogenesis 在含有透明质酸-岩藻聚糖的3d打印支架中，重组VEGF和merwinite纳米颗粒对颅面骨血管生成的影响

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-12-02 DOI: 10.1016/j.ejpb.2025.114944

Elaf Mahmood Shihab , Rafif Raad , Saba Naseer Abbas , Maha Hameed Al-bahrani , Mastafa H. Al-Musawi , Hashim H. Al Zuaini , Farah E. Ismaeel , Sheida Mani , Fariborz Sharifianjazi , Ketevan Tavamaishvili , Marjan Mirhaj , Mohamadreza Tavakoli

Craniofacial fractures present intricate geometries that require defect-matched scaffolds for effective regeneration. Advanced 3D printing enables the fabrication of anatomically tailored structures, making it a powerful tool in bone tissue engineering. In this study, a novel 3D-printed scaffold integrating polyvinyl alcohol (PVA), hyaluronic acid (HA), fucoidan (Fc), and merwinite (Mr) nanoparticles with recombinant VEGF was developed as a multifunctional platform, with the aim of promoting both osteogenesis and angiogenesis in complex craniofacial defects. The HA.Fc.VEGF.Mr scaffold exhibited a compressive strength of 3.19 ± 0.11 MPa and an elastic modulus of 21.75 ± 3.32 MPa, making it suitable for craniofacial bone repair. After 28 days of immersion in PBS, the scaffold showed a degradation rate of 50.6 ± 4.6 %, while VEGF release reached 95.1 ± 5.1 % in a sustained, linear pattern by day 11. Bioactivity was validated through apatite-like deposition in SBF immersion for 28 days, alongside measurable release of Ca²⁺, Si⁴⁺, and Mg²⁺ ions. In vitro assessments demonstrated high cytocompatibility and enhanced osteogenic activity, confirmed by ALP levels, calcium deposition, and the upregulation of COL1, RUNX2, and osteocalcin. Angiogenic potential was further validated using the CAM assay, where the HA.Fc.VEGF.Mr scaffold exhibited superior neovascularization compared to other groups. These findings demonstrate the multifunctionality and regenerative potential of this scaffold for craniofacial bone repair.

颅面骨折呈现复杂的几何形状，需要缺损匹配的支架进行有效的再生。先进的3D打印技术使解剖学定制结构的制造成为可能，使其成为骨组织工程的有力工具。在这项研究中，一种新型的3d打印支架将聚乙烯醇（PVA）、透明质酸（HA）、岩藻聚糖（Fc）和墨文石（Mr）纳米颗粒与重组VEGF结合在一起，作为多功能平台，旨在促进复杂颅面缺损的骨生成和血管生成。HA.Fc.VEGF.Mr支架抗压强度为3.19±0.11 MPa，弹性模量为21.75±3.32 MPa，适用于颅面骨修复。在PBS中浸泡28天后，支架的降解率为50.6±4.6%，到第11天，VEGF的持续线性释放达到95.1±5.1%。生物活性通过在SBF浸泡28天的磷灰石样沉积来验证，同时释放可测量的Ca2+， Si4+和Mg2+离子。体外评估显示高细胞相容性和增强的成骨活性，证实了ALP水平，钙沉积，COL1， RUNX2和骨钙素上调。CAM实验进一步验证了血管生成潜力，与其他组相比，HA.Fc.VEGF.Mr支架表现出优越的新生血管。这些发现证明了该支架用于颅面骨修复的多功能性和再生潜力。

{"title":"The effect of recombinant VEGF and merwinite nanoparticles within a 3D-printed scaffold containing hyaluronic acid–fucoidan on craniofacial osteoangiogenesis","authors":"Elaf Mahmood Shihab , Rafif Raad , Saba Naseer Abbas , Maha Hameed Al-bahrani , Mastafa H. Al-Musawi , Hashim H. Al Zuaini , Farah E. Ismaeel , Sheida Mani , Fariborz Sharifianjazi , Ketevan Tavamaishvili , Marjan Mirhaj , Mohamadreza Tavakoli","doi":"10.1016/j.ejpb.2025.114944","DOIUrl":"10.1016/j.ejpb.2025.114944","url":null,"abstract":"<div><div>Craniofacial fractures present intricate geometries that require defect-matched scaffolds for effective regeneration. Advanced 3D printing enables the fabrication of anatomically tailored structures, making it a powerful tool in bone tissue engineering. In this study, a novel 3D-printed scaffold integrating polyvinyl alcohol (PVA), hyaluronic acid (HA), fucoidan (Fc), and merwinite (Mr) nanoparticles with recombinant VEGF was developed as a multifunctional platform, with the aim of promoting both osteogenesis and angiogenesis in complex craniofacial defects. The HA.Fc.VEGF.Mr scaffold exhibited a compressive strength of 3.19 ± 0.11 MPa and an elastic modulus of 21.75 ± 3.32 MPa, making it suitable for craniofacial bone repair. After 28 days of immersion in PBS, the scaffold showed a degradation rate of 50.6 ± 4.6 %, while VEGF release reached 95.1 ± 5.1 % in a sustained, linear pattern by day 11. Bioactivity was validated through apatite-like deposition in SBF immersion for 28 days, alongside measurable release of Ca<sup>2+</sup>, Si<sup>4+</sup>, and Mg<sup>2+</sup> ions. <em>In vitro</em> assessments demonstrated high cytocompatibility and enhanced osteogenic activity, confirmed by ALP levels, calcium deposition, and the upregulation of COL1, RUNX2, and osteocalcin. Angiogenic potential was further validated using the CAM assay, where the HA.Fc.VEGF.Mr scaffold exhibited superior neovascularization compared to other groups. These findings demonstrate the multifunctionality and regenerative potential of this scaffold for craniofacial bone repair.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"219 ","pages":"Article 114944"},"PeriodicalIF":4.3,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inclusion complex of carbamazepine and hydroxypropyl-β-cyclodextrin enhances nose-to-brain delivery via improved solubility 卡马西平和羟丙基-β-环糊精包合物通过改善溶解度增强鼻-脑递送。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-11-27 DOI: 10.1016/j.ejpb.2025.114942

Takuhiro Totoki , Koki Ogawa , Tetsuya Ozeki

Intranasal delivery offers a non-invasive route for transporting drugs to the brain by bypassing the blood–brain barrier. However, the limited fluid volume in the nasal cavity restricts the solubilization of poorly water-soluble drugs such as carbamazepine (CBZ). In this study, we developed an inclusion complex of CBZ with hydroxypropyl-β-cyclodextrin (HP-βCD) to enhance its solubility and facilitate nose-to-brain delivery. Phase solubility analysis and Job’s plot confirmed the formation of a 1:1 complex. Powder formulations were prepared via freeze-drying and spray freeze-drying. The powders completely dissolved within 5 min and maintained their amorphous state during long-term storage. Intranasal administration of the CBZ/HP-βCD complex powders in rats resulted in significantly improved brain uptake compared with that of the CBZ bulk drug or physical mixtures. Notably, the brain-to-plasma ratio was higher for powder formulations than for liquids, suggesting enhanced direct transport to the brain. Regional brain distribution analysis revealed predominant accumulation in the olfactory bulb, likely because of its anatomical proximity and neural connections with the nasal cavity. Although this pattern is commonly observed during nose-to-brain delivery, it may limit drug access to deeper brain regions. Therefore, further optimization　using targeted strategies or delivery enhancers is required. Overall, HP-βCD inclusion complexation represents a promising approach to improve solubility, stability, and brain delivery efficiency of poorly soluble CNS-active drugs following intranasal administration.

鼻内给药为绕过血脑屏障将药物输送到大脑提供了一种非侵入性途径。然而，鼻腔内有限的液体容量限制了卡马西平（CBZ）等水溶性较差的药物的增溶。在这项研究中，我们开发了一种CBZ与羟丙基-β-环糊精（HP-βCD）的包合物，以提高其溶解度并促进鼻-脑递送。相溶解度分析和约伯图证实了1:1配合物的形成。通过冷冻干燥和喷雾冷冻干燥制备了粉末配方。粉末在5 min内完全溶解，并在长期储存中保持无定形状态。与CBZ原料药或物理混合物相比，大鼠鼻内给药CBZ/HP-βCD复合物粉末可显著改善脑摄取。值得注意的是，粉末配方的脑与血浆比率高于液体配方，这表明直接输送到大脑的能力增强。脑区域分布分析显示，主要积聚在嗅球，可能是因为其解剖接近和与鼻腔的神经连接。虽然这种模式通常在鼻到脑给药过程中观察到，但它可能限制药物进入更深的大脑区域。因此，需要使用目标策略或交付增强器进行进一步优化。总的来说，HP-βCD包合是一种很有前途的方法，可以改善鼻内给药后难溶性中枢神经系统活性药物的溶解度、稳定性和脑递送效率。

{"title":"Inclusion complex of carbamazepine and hydroxypropyl-β-cyclodextrin enhances nose-to-brain delivery via improved solubility","authors":"Takuhiro Totoki , Koki Ogawa , Tetsuya Ozeki","doi":"10.1016/j.ejpb.2025.114942","DOIUrl":"10.1016/j.ejpb.2025.114942","url":null,"abstract":"<div><div>Intranasal delivery offers a non-invasive route for transporting drugs to the brain by bypassing the blood–brain barrier. However, the limited fluid volume in the nasal cavity restricts the solubilization of poorly water-soluble drugs such as carbamazepine (CBZ). In this study, we developed an inclusion complex of CBZ with hydroxypropyl-β-cyclodextrin (HP-βCD) to enhance its solubility and facilitate nose-to-brain delivery. Phase solubility analysis and Job’s plot confirmed the formation of a 1:1 complex. Powder formulations were prepared via freeze-drying and spray freeze-drying. The powders completely dissolved within 5 min and maintained their amorphous state during long-term storage. Intranasal administration of the CBZ/HP-βCD complex powders in rats resulted in significantly improved brain uptake compared with that of the CBZ bulk drug or physical mixtures. Notably, the brain-to-plasma ratio was higher for powder formulations than for liquids, suggesting enhanced direct transport to the brain. Regional brain distribution analysis revealed predominant accumulation in the olfactory bulb, likely because of its anatomical proximity and neural connections with the nasal cavity. Although this pattern is commonly observed during nose-to-brain delivery, it may limit drug access to deeper brain regions. Therefore, further optimization　using targeted strategies or delivery enhancers is required. Overall, HP-βCD inclusion complexation represents a promising approach to improve solubility, stability, and brain delivery efficiency of poorly soluble CNS-active drugs following intranasal administration.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"218 ","pages":"Article 114942"},"PeriodicalIF":4.3,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145631482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Probing in vivo drug release of macrophage-targeting liposomes 巨噬细胞靶向脂质体的体内药物释放探测

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-11-25 DOI: 10.1016/j.ejpb.2025.114941

Hongling Xu , Yangxue Su , Hailong Ma , Xin Zeng , Manlin Wang , Weijie Chen , Xingyu Chen , Qing Zhou , Yang Li , Yaxin Zheng

Macrophages can internalize liposomes and disrupt them to facilitate drug release in the body. However, the effect of targeting liposomes to macrophages on in vivo drug release remains unclear. In this study, we compared the in vivo drug release from macrophage-targeting liposomes (modified with 1,2-distearoyl phosphatidylserine, PS) and PEGylated liposomes in 4 T1 breast tumor-bearing mice. The macrophage-targeting capability of PS-modified liposomes was confirmed by their significantly enhanced cellular uptake in macrophages compared to that of PEGylated liposomes. In vivo drug release studies showed that PS-modified liposomes exhibited higher drug release in various tissues than that of PEGylated liposomes, suggesting that macrophages facilitate the release of the drug from liposomes in the body. Despite a higher percentage of drug release in the tumor, the PS-modified liposomes did not improve antitumor activity compared to PEGylated liposomes due to their rapid clearance. These results suggest that targeting liposomes to macrophages can enhance in vivo drug release but fail to increase antitumor activity due to low tumor selectivity. Therefore, selectively targeting liposomes to tumor-associated macrophages is essential for boosting antitumor effects.

巨噬细胞可以内化脂质体并破坏它们以促进药物在体内的释放。然而，脂质体靶向巨噬细胞对体内药物释放的影响尚不清楚。在这项研究中，我们比较了巨噬细胞靶向脂质体（1,2-二硬脂酰磷脂酰丝氨酸，PS修饰）和聚乙二醇化脂质体在4只T1乳腺荷瘤小鼠体内的药物释放情况。与聚乙二醇化脂质体相比，ps修饰脂质体在巨噬细胞中的细胞摄取显著增强，证实了其巨噬细胞靶向能力。体内药物释放研究表明，ps修饰脂质体在各组织中的药物释放均高于聚乙二醇化脂质体，提示巨噬细胞促进了体内脂质体的药物释放。尽管肿瘤中药物释放的百分比更高，但由于ps修饰脂质体的快速清除，与聚乙二醇修饰脂质体相比，其抗肿瘤活性并没有提高。这些结果表明，将脂质体靶向巨噬细胞可以促进体内药物释放，但由于肿瘤选择性低，不能提高抗肿瘤活性。因此，选择性地将脂质体靶向肿瘤相关巨噬细胞对于增强抗肿瘤作用至关重要。

{"title":"Probing in vivo drug release of macrophage-targeting liposomes","authors":"Hongling Xu , Yangxue Su , Hailong Ma , Xin Zeng , Manlin Wang , Weijie Chen , Xingyu Chen , Qing Zhou , Yang Li , Yaxin Zheng","doi":"10.1016/j.ejpb.2025.114941","DOIUrl":"10.1016/j.ejpb.2025.114941","url":null,"abstract":"<div><div>Macrophages can internalize liposomes and disrupt them to facilitate drug release in the body. However, the effect of targeting liposomes to macrophages on <em>in vivo</em> drug release remains unclear. In this study, we compared the <em>in vivo</em> drug release from macrophage-targeting liposomes (modified with 1,2-distearoyl phosphatidylserine, PS) and PEGylated liposomes in 4 T1 breast tumor-bearing mice. The macrophage-targeting capability of PS-modified liposomes was confirmed by their significantly enhanced cellular uptake in macrophages compared to that of PEGylated liposomes. <em>In vivo</em> drug release studies showed that PS-modified liposomes exhibited higher drug release in various tissues than that of PEGylated liposomes, suggesting that macrophages facilitate the release of the drug from liposomes in the body. Despite a higher percentage of drug release in the tumor, the PS-modified liposomes did not improve antitumor activity compared to PEGylated liposomes due to their rapid clearance. These results suggest that targeting liposomes to macrophages can enhance <em>in vivo</em> drug release but fail to increase antitumor activity due to low tumor selectivity. Therefore, selectively targeting liposomes to tumor-associated macrophages is essential for boosting antitumor effects.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"218 ","pages":"Article 114941"},"PeriodicalIF":4.3,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel histidine-acetate buffer for freeze-dried monoclonal antibody formulations 一种用于冻干单克隆抗体制剂的新型组氨酸-醋酸酯缓冲液

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-11-25 DOI: 10.1016/j.ejpb.2025.114940

Jia-Yi Lv , Han Gao , Huan-Fang Xie , Meng-Jia Jin , Bin Di , Jin Xu , Wei-Jie Fang

Histidine (His)-hydrochloride (HCl) is widely used in freeze-dried monoclonal antibody (mAb) formulations, but alternative buffers are required when chloride ions are undesirable. This study evaluates His-acetate (Ac) as a substitute and its impact on the stability of two model mAbs with distinct physicochemical properties— infliximab (mAb-1) and a humanized anti-ricin mAb (mAb-2). pH shifts during freeze-drying were compared among His-Ac, His-HCl, and sodium Ac buffers, confirming strong buffering capacity of His-Ac within pH 5.5–6.5. Conformational and colloidal stability assessments revealed that both mAbs displayed higher melting temperatures or favorable diffusion interaction parameters in His-Ac formulations. Moreover, mAb-2 exhibited a higher collapse temperature in His-Ac compared to His-HCl, indicating improved structural integrity or drying efficiency during primary drying. No significant differences were observed in aggregation onset temperature and glass transition temperature. Aggregation and chemical stability under stress conditions were evaluated by micro-flow imaging, size exclusion chromatography, and ion exchange chromatography. No notable changes in subvisible particle counts or monomer content occurred after freeze-drying. Overall, His-Ac demonstrated stability comparable to or better than His-HCl, supporting its use in freeze-dried mAb formulations.

组氨酸(His)-盐酸（HCl）广泛用于冻干单克隆抗体（mAb）制剂，但当不需要氯离子时，需要替代缓冲液。本研究评估了His-acetate （Ac）作为替代品及其对两种具有不同物理化学性质的模型单抗-英夫利昔单抗（mAb-1）和人源抗蓖麻毒素单抗（mAb-2）稳定性的影响。比较了His-Ac、His-HCl和Ac钠缓冲液在冷冻干燥过程中的pH变化，证实了His-Ac缓冲液在pH值5.5-6.5之间具有较强的缓冲能力。构象和胶体稳定性评估表明，这两种单抗在His-Ac配方中具有更高的熔化温度或有利的扩散相互作用参数。此外，与His-HCl相比，mAb-2在His-Ac中表现出更高的坍塌温度，表明初次干燥时结构完整性或干燥效率得到改善。聚合起始温度和玻璃化转变温度无显著差异。通过微流成像、尺寸排除层析和离子交换层析来评价应力条件下的聚集性和化学稳定性。冷冻干燥后，不可见颗粒计数或单体含量无明显变化。总体而言，His-Ac表现出与His-HCl相当或更好的稳定性，支持其在冻干单抗制剂中的应用。

{"title":"A novel histidine-acetate buffer for freeze-dried monoclonal antibody formulations","authors":"Jia-Yi Lv , Han Gao , Huan-Fang Xie , Meng-Jia Jin , Bin Di , Jin Xu , Wei-Jie Fang","doi":"10.1016/j.ejpb.2025.114940","DOIUrl":"10.1016/j.ejpb.2025.114940","url":null,"abstract":"<div><div>Histidine (His)-hydrochloride (HCl) is widely used in freeze-dried monoclonal antibody (mAb) formulations, but alternative buffers are required when chloride ions are undesirable. This study evaluates His-acetate (Ac) as a substitute and its impact on the stability of two model mAbs with distinct physicochemical properties— infliximab (mAb-1) and a humanized anti-ricin mAb (mAb-2). pH shifts during freeze-drying were compared among His-Ac, His-HCl, and sodium Ac buffers, confirming strong buffering capacity of His-Ac within pH 5.5–6.5. Conformational and colloidal stability assessments revealed that both mAbs displayed higher melting temperatures or favorable diffusion interaction parameters in His-Ac formulations. Moreover, mAb-2 exhibited a higher collapse temperature in His-Ac compared to His-HCl, indicating improved structural integrity or drying efficiency during primary drying. No significant differences were observed in aggregation onset temperature and glass transition temperature. Aggregation and chemical stability under stress conditions were evaluated by micro-flow imaging, size exclusion chromatography, and ion exchange chromatography. No notable changes in subvisible particle counts or monomer content occurred after freeze-drying. Overall, His-Ac demonstrated stability comparable to or better than His-HCl, supporting its use in freeze-dried mAb formulations.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"218 ","pages":"Article 114940"},"PeriodicalIF":4.3,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Naproxen printlets for extemporaneous dispersion: Designing new medicines for drug delivery through the enteral route 临时分散的萘普生小片：设计通过肠内途径给药的新药。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-11-23 DOI: 10.1016/j.ejpb.2025.114939

Nadine Lysyk Funk , Flávia Carvalho Tavaniello , Edilson Valmir Benvenutti , Cesar Liberato Petzhold , Karina Paese , Monique Deon , Ruy Carlos Beck

Off-label use of medicines administered via enteral feeding tubes (EFT) can lead to dose inaccuracies, adverse effects and tube obstruction, compromising therapeutic outcomes. Thus, new manufacturing processes are required to design medicines specifically for EFT administration. In this study, a 3D printing semi-solid extrusion (SSE) technique was employed to produce circular-shaped naproxen printlets (P-NPX) (18 × 18 × 2.6 mm, 30 % infill) for aqueous dispersion prior to EFT administration. Mesoporous silica nanoparticles (MSN) were used as NPX nanocarriers for development of printlets (P-NPX-MSN). Results show that MSN drug encapsulation enabled production of printlets with reproducible NPX content, without organic solvents; while providing better shape retention. Aqueous dispersion times were 806 ± 26 s for P-NPX and 813 ± 20 s for P-NPX-MSN. For both formulations, resulting dispersions were slightly acidic (pH ∼ 5), with viscosity of 1.3 cP and particle size distribution that ensured NPX administration without tube obstruction. Drug recovery was ∼ 100 % for both formulations after tube passage. Re-dispersed printlets had reduced vascular event compared to positive controls in Hen’s Egg Test − Chorioallantoic Membrane (HET-CAM) assay (in vitro alternative model) and were classified as slight irritants. This study provides an innovative route for drugs presenting gastric irritation, advancing SSE 3D printing for personalised EFT medicines.

经肠内喂养管（EFT）给药的超说明书使用可导致剂量不准确、不良反应和管阻塞，影响治疗结果。因此，需要新的制造工艺来设计专门用于EFT管理的药物。在这项研究中，采用3D打印半固体挤压（SSE）技术，在EFT给药之前，生产出圆形的萘普生小块（P-NPX）（18 × 18 × 2.6 mm， 30 %填充）用于水分散。以介孔二氧化硅纳米颗粒（MSN）为NPX纳米载体，制备了P-NPX-MSN微球。结果表明，单分散微球药物包封可以在不使用有机溶剂的情况下制备具有可重复性的NPX含量的小片；同时提供更好的形状保持。P-NPX水溶液分散时间为806 ± 26 s， P-NPX- msn水溶液分散时间为813 ± 20 s。对于这两种配方，得到的分散体都是微酸性的（pH ~ 5），粘度为1.3 cP，粒径分布确保NPX给药不会堵塞管道。两种制剂通过试管后的药物回收率均为 ~ 100% %。在鸡蛋试验-绒毛膜-尿囊膜（et - cam）试验（体外替代模型）中，与阳性对照相比，再分散的小细胞血管事件减少，并被归类为轻微刺激物。这项研究为胃刺激药物提供了一条创新途径，推动了SSE 3D打印个性化EFT药物的发展。

{"title":"Naproxen printlets for extemporaneous dispersion: Designing new medicines for drug delivery through the enteral route","authors":"Nadine Lysyk Funk , Flávia Carvalho Tavaniello , Edilson Valmir Benvenutti , Cesar Liberato Petzhold , Karina Paese , Monique Deon , Ruy Carlos Beck","doi":"10.1016/j.ejpb.2025.114939","DOIUrl":"10.1016/j.ejpb.2025.114939","url":null,"abstract":"<div><div>Off-label use of medicines administered via enteral feeding tubes (EFT) can lead to dose inaccuracies, adverse effects and tube obstruction, compromising therapeutic outcomes. Thus, new manufacturing processes are required to design medicines specifically for EFT administration. In this study, a 3D printing semi-solid extrusion (SSE) technique was employed to produce circular-shaped naproxen printlets (P-NPX) (18 × 18 × 2.6 mm, 30 % infill) for aqueous dispersion prior to EFT administration. Mesoporous silica nanoparticles (MSN) were used as NPX nanocarriers for development of printlets (P-NPX-MSN). Results show that MSN drug encapsulation enabled production of printlets with reproducible NPX content, without organic solvents; while providing better shape retention. Aqueous dispersion times were 806 ± 26 s for P-NPX and 813 ± 20 s for P-NPX-MSN. For both formulations, resulting dispersions were slightly acidic (pH ∼ 5), with viscosity of 1.3 cP and particle size distribution that ensured NPX administration without tube obstruction. Drug recovery was ∼ 100 % for both formulations after tube passage. Re-dispersed printlets had reduced vascular event compared to positive controls in Hen’s Egg Test − Chorioallantoic Membrane (HET-CAM) assay (in vitro alternative model) and were classified as slight irritants. This study provides an innovative route for drugs presenting gastric irritation, advancing SSE 3D printing for personalised EFT medicines.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"218 ","pages":"Article 114939"},"PeriodicalIF":4.3,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Paclitaxel and rose bengal loaded microbubbles for the ultrasound targeted chemo-sonodynamic therapy of pancreatic cancer 紫杉醇和玫瑰花负载微泡用于超声靶向化疗-声动力治疗胰腺癌。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-11-19 DOI: 10.1016/j.ejpb.2025.114937

Jack Wright , Keiran Logan , Thomas McKaig , Sukanta Kamila , Chloe McClenaghan , Heather Nesbitt , Mark A. Taylor , Mark Love , Eleanor Stride , Jia-Ling Ruan , Anthony P. McHale , John F. Callan

Despite significant advances in cancer treatment over the past five decades, survival outcomes for pancreatic cancer have remained largely unchanged. The effectiveness of chemotherapy as a treatment for pancreatic cancer is limited by the dense, protective tumour stroma, which impedes drug delivery. Ultrasound-targeted microbubble destruction (UTMD) has emerged as a promising strategy for enhancing the delivery of chemotherapy agents to solid tumours. In this study, we report the development and evaluation of a novel microbubble (MB) formulation, ST-001, which incorporates paclitaxel chemotherapy and a Rose Bengal sonosensitiser for targeted chemo-sonodynamic therapy of pancreatic cancer. The principle of UTMD using ST-001 was demonstrated in a murine model of pancreatic cancer, where B-mode ultrasound imaging was used to visualize MB accumulation within the tumour and its subsequent clearance following the application of therapeutic ultrasound. Preclinical efficacy studies demonstrated a significant survival advantage in ST-001 treated mice, which survived more than twice as long as those treated with standard Taxol, despite receiving only 14% of the paclitaxel dose. Additionally, a preclinical toxicology study in healthy mice demonstrated an excellent safety profile for ST-001, with no adverse effects observed in key hematological and blood biochemical markers, or in the histology of the spleen, liver, and kidneys.

尽管在过去的50年里，癌症治疗取得了重大进展，但胰腺癌的生存结果在很大程度上保持不变。化疗作为胰腺癌治疗的有效性受到致密的保护性肿瘤基质的限制，这阻碍了药物的传递。超声靶向微泡破坏（UTMD）已成为一种有前途的策略，以加强化疗药物的递送到实体肿瘤。在这项研究中，我们报道了一种新型微泡（MB）制剂ST-001的开发和评估，ST-001结合紫杉醇化疗和玫瑰孟加拉声敏剂用于靶向化疗-声动力治疗胰腺癌。使用ST-001的UTMD原理在小鼠胰腺癌模型中得到证实，其中使用b型超声成像来观察肿瘤内MB的积累以及应用治疗性超声后MB的清除。临床前疗效研究表明，ST-001治疗小鼠具有显著的生存优势，尽管仅接受14%的紫杉醇剂量，但其存活时间是标准紫杉醇治疗小鼠的两倍多。此外，一项针对健康小鼠的临床前毒理学研究表明，ST-001具有良好的安全性，在关键的血液学和血液生化指标，以及脾脏、肝脏和肾脏的组织学中没有观察到不良反应。

{"title":"Paclitaxel and rose bengal loaded microbubbles for the ultrasound targeted chemo-sonodynamic therapy of pancreatic cancer","authors":"Jack Wright , Keiran Logan , Thomas McKaig , Sukanta Kamila , Chloe McClenaghan , Heather Nesbitt , Mark A. Taylor , Mark Love , Eleanor Stride , Jia-Ling Ruan , Anthony P. McHale , John F. Callan","doi":"10.1016/j.ejpb.2025.114937","DOIUrl":"10.1016/j.ejpb.2025.114937","url":null,"abstract":"<div><div>Despite significant advances in cancer treatment over the past five decades, survival outcomes for pancreatic cancer have remained largely unchanged. The effectiveness of chemotherapy as a treatment for pancreatic cancer is limited by the dense, protective tumour stroma, which impedes drug delivery. Ultrasound-targeted microbubble destruction (UTMD) has emerged as a promising strategy for enhancing the delivery of chemotherapy agents to solid tumours. In this study, we report the development and evaluation of a novel microbubble (MB) formulation, ST-001, which incorporates paclitaxel chemotherapy and a Rose Bengal sonosensitiser for targeted chemo-sonodynamic therapy of pancreatic cancer. The principle of UTMD using ST-001 was demonstrated in a murine model of pancreatic cancer, where B-mode ultrasound imaging was used to visualize MB accumulation within the tumour and its subsequent clearance following the application of therapeutic ultrasound. Preclinical efficacy studies demonstrated a significant survival advantage in ST-001 treated mice, which survived more than twice as long as those treated with standard Taxol, despite receiving only 14% of the paclitaxel dose. Additionally, a preclinical toxicology study in healthy mice demonstrated an excellent safety profile for ST-001, with no adverse effects observed in key hematological and blood biochemical markers, or in the histology of the spleen, liver, and kidneys.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"218 ","pages":"Article 114937"},"PeriodicalIF":4.3,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

N-acetylcysteine loaded electrospun core/shell nanofibers: a promising system for ferroptosis in spinal cord injury 负载n -乙酰半胱氨酸的电纺核/壳纳米纤维：一种有前途的脊髓损伤铁下垂系统。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-11-19 DOI: 10.1016/j.ejpb.2025.114938

Meliha Gunes , Gizem Kaftan Öcal , Bünyamin Kılıclı , Anıl Murat Ozturk , Güliz Armagan , Sinem Yaprak Karavana

Spinal cord injury (SCI) induces a cascade of secondary damage mechanisms, including oxidative stress, inflammation, and cell death, which severely impair neuronal recovery. In this study, N-acetylcysteine (NAC), a thiol-based antioxidant with limited CNS bioavailability, was encapsulated in polycaprolactone (PCL) nanofibers using emulsion electrospinning. This approach allows localized and sustained drug delivery. Span 80 and Poloxamer 407 were used as surfactants to stabilize the emulsion and increase the hydrophilicity of the fibers. The resulting core/shell nanofibers (NAC-CSN) exhibited uniform morphology, improved wettability, and favorable mechanical properties, while supporting cell viability and migration in vitro. Sustained NAC release over several days was achieved, indicating diffusion-controlled delivery. In a rat model of SCI, NAC-CSN treatment attenuated oxidative and ferroptotic damage and promoted early neuroregeneration, which enabled measurable locomotor recovery. These findings suggest that NAC-CSN scaffolds offer an effective neuroprotective strategy against secondary SCI damage and, by enabling localized antioxidant delivery at the lesion site, represent a clinically applicable platform for future tissue engineering and translational therapies.

脊髓损伤（SCI）引起一系列继发性损伤机制，包括氧化应激、炎症和细胞死亡，严重损害神经元的恢复。本研究采用乳液静电纺丝技术，将具有有限中枢神经系统生物利用度的巯基抗氧化剂n -乙酰半胱氨酸（NAC）包被在聚己内酯（PCL）纳米纤维中。这种方法允许局部和持续给药。用Span 80和poloxam407作为表面活性剂稳定乳液，提高纤维的亲水性。所得到的核/壳纳米纤维（NAC-CSN）具有均匀的形态、更好的润湿性和良好的机械性能，同时支持细胞的体外活力和迁移。NAC在数天内持续释放，表明扩散控制输送。在脊髓损伤大鼠模型中，NAC-CSN治疗可减轻氧化性和铁性损伤，促进早期神经再生，从而实现可测量的运动恢复。这些发现表明，NAC-CSN支架提供了一种有效的神经保护策略，可以抵抗继发性脊髓损伤，并且通过在病变部位进行局部抗氧化剂递送，代表了未来组织工程和转化治疗的临床应用平台。

{"title":"N-acetylcysteine loaded electrospun core/shell nanofibers: a promising system for ferroptosis in spinal cord injury","authors":"Meliha Gunes , Gizem Kaftan Öcal , Bünyamin Kılıclı , Anıl Murat Ozturk , Güliz Armagan , Sinem Yaprak Karavana","doi":"10.1016/j.ejpb.2025.114938","DOIUrl":"10.1016/j.ejpb.2025.114938","url":null,"abstract":"<div><div>Spinal cord injury (SCI) induces a cascade of secondary damage mechanisms, including oxidative stress, inflammation, and cell death, which severely impair neuronal recovery. In this study, N-acetylcysteine (NAC), a thiol-based antioxidant with limited CNS bioavailability, was encapsulated in polycaprolactone (PCL) nanofibers using emulsion electrospinning. This approach allows localized and sustained drug delivery. Span 80 and Poloxamer 407 were used as surfactants to stabilize the emulsion and increase the hydrophilicity of the fibers. The resulting core/shell nanofibers (NAC-CSN) exhibited uniform morphology, improved wettability, and favorable mechanical properties, while supporting cell viability and migration <em>in vitro</em>. Sustained NAC release over several days was achieved, indicating diffusion-controlled delivery. In a rat model of SCI, NAC-CSN treatment attenuated oxidative and ferroptotic damage and promoted early neuroregeneration, which enabled measurable locomotor recovery. These findings suggest that NAC-CSN scaffolds offer an effective neuroprotective strategy against secondary SCI damage and, by enabling localized antioxidant delivery at the lesion site, represent a clinically applicable platform for future tissue engineering and translational therapies.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"218 ","pages":"Article 114938"},"PeriodicalIF":4.3,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to “Enhancement in site-specific delivery of carvacrol for potential treatment of infected wounds using infection responsive nanoparticles loaded into dissolving microneedles: A proof of concept study.” [Eur. J. Pharm. Biopharm. 147 (2020) 57–68] “将感染反应性纳米颗粒装载到溶解性微针中，增强对感染伤口潜在治疗的特定部位的卡维罗的递送：概念验证研究”的更正。(欧元。j .制药。生物医学工程学报，2014(5):557 - 568。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-11-17 DOI: 10.1016/j.ejpb.2025.114927

Maria Mir , Andi Dian Permana , Naveed Ahmed , Gul Majid Khan , Asim ur Rehman , Ryan F. Donnelly

引用次数: 0

In vitro two stage one compartment dumping test data and absorption/formulation PBBM modeling to explain a bioequivalence failure of valsartan formulations 体外两阶段一室倾倒试验数据和吸收/配方PBBM模型来解释缬沙坦配方的生物等效性失败。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-11-17 DOI: 10.1016/j.ejpb.2025.114932

Bárbara Sánchez-Dengra, Alejandro Ruiz-Picazo, Isabel Gonzalez-Alvarez, Marta Gonzalez-Alvarez, Marival Bermejo

Background

In recent years, significant efforts have been made to develop new dissolution methods capable of predicting the in vivo behavior of pharmaceutical formulations. This is essential for establishing valid in vitro-in vivo correlations (IVIVCs) and biopredictive models. However, many of these methodologies involve sophisticated, costly, and complex devices designed to replicate human physiology. The objective of this study was to predict in vivo bioequivalence (BE) using a simplified dynamic dissolution methodology and to establish a physiologically based biopharmaceutics model (PBBM).

Methods

An oral fixed-dose combination of valsartan (VALS, BCS Class IV) and hydrochlorothiazide (HCTZ, BCS Class III) was used for the study. The reference product (Co-Diovan® Forte) and two generic formulations were evaluated using a dissolution approach. A two stage one compartment dissolution technique, known as the “dumping test,” was applied to assess drug release profiles. The in vitro dissolution data obtained were incorporated into the PBBM, with two scaling factors—one for time and another for absorption—to enhance predictive accuracy.

Results

The “dumping test” successfully simulated the different dissolution behaviors of the formulations and explained the failure of bioequivalence in certain cases. The established IVIVC demonstrated both validity and biopredictive capability. The percentage prediction errors (% PEs) for the PBBM, after incorporating in vitro data and the scaling factors, remained within acceptable regulatory limits.

Conclusions

The study demonstrated that a simple dynamic dissolution methodology can effectively predict in vivo bioequivalence and formulation performance. The application of the “dumping test” provided valuable insights into the dissolution characteristics of different formulations, highlighting its potential as a cost-effective and practical tool for biopredictive studies.

背景：近年来，人们在开发能够预测药物制剂体内行为的新的溶出度方法方面做出了重大努力。这对于建立有效的体内外相关性（IVIVCs）和生物预测模型至关重要。然而，许多这些方法涉及复杂、昂贵和复杂的设备，旨在复制人体生理学。本研究的目的是使用简化的动态溶出度方法预测体内生物等效性（BE），并建立一个基于生理学的生物制药模型（PBBM）。方法：采用缬沙坦（VALS， BCS IV类）和氢氯噻嗪（HCTZ， BCS III类）口服固定剂量联合用药进行研究。采用溶出度法对参比制剂（Co-Diovan®Forte）和两种仿制制剂进行评价。一种被称为“倾倒试验”的两阶段一室溶出技术被用于评估药物释放概况。将获得的体外溶出度数据纳入PBBM，并使用两个比例因子-一个是时间因子，另一个是吸收因子-以提高预测准确性。结果：“倾倒试验”成功地模拟了制剂的不同溶出行为，并解释了某些情况下生物等效性的失败。所建立的IVIVC具有良好的有效性和生物预测能力。在结合体外数据和比例因子后，PBBM的预测误差百分比（% PEs）仍在可接受的监管范围内。结论：简单的动态溶出度方法可有效预测制剂的体内生物等效性和制剂性能。“倾倒试验”的应用为了解不同制剂的溶出特性提供了有价值的见解，突出了其作为生物预测研究的成本效益和实用工具的潜力。

{"title":"In vitro two stage one compartment dumping test data and absorption/formulation PBBM modeling to explain a bioequivalence failure of valsartan formulations","authors":"Bárbara Sánchez-Dengra, Alejandro Ruiz-Picazo, Isabel Gonzalez-Alvarez, Marta Gonzalez-Alvarez, Marival Bermejo","doi":"10.1016/j.ejpb.2025.114932","DOIUrl":"10.1016/j.ejpb.2025.114932","url":null,"abstract":"<div><h3>Background</h3><div>In recent years, significant efforts have been made to develop new dissolution methods capable of predicting the in vivo behavior of pharmaceutical formulations. This is essential for establishing valid in vitro-in vivo correlations (IVIVCs) and biopredictive models. However, many of these methodologies involve sophisticated, costly, and complex devices designed to replicate human physiology. The objective of this study was to predict in vivo bioequivalence (BE) using a simplified dynamic dissolution methodology and to establish a physiologically based biopharmaceutics model (PBBM).</div></div><div><h3>Methods</h3><div>An oral fixed-dose combination of valsartan (VALS, BCS Class IV) and hydrochlorothiazide (HCTZ, BCS Class III) was used for the study. The reference product (Co-Diovan® Forte) and two generic formulations were evaluated using a dissolution approach. A two stage one compartment dissolution technique, known as the “dumping test,” was applied to assess drug release profiles. The in vitro dissolution data obtained were incorporated into the PBBM, with two scaling factors—one for time and another for absorption—to enhance predictive accuracy.</div></div><div><h3>Results</h3><div>The “dumping test” successfully simulated the different dissolution behaviors of the formulations and explained the failure of bioequivalence in certain cases. The established IVIVC demonstrated both validity and biopredictive capability. The percentage prediction errors (% PEs) for the PBBM, after incorporating in vitro data and the scaling factors, remained within acceptable regulatory limits.</div></div><div><h3>Conclusions</h3><div>The study demonstrated that a simple dynamic dissolution methodology can effectively predict in vivo bioequivalence and formulation performance. The application of the “dumping test” provided valuable insights into the dissolution characteristics of different formulations, highlighting its potential as a cost-effective and practical tool for biopredictive studies.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"218 ","pages":"Article 114932"},"PeriodicalIF":4.3,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Does slowly reversible binding to keratin contribute to stratum corneum reservoir function? 与角蛋白的缓慢可逆结合是否有助于角质层储层功能？

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-11-17 DOI: 10.1016/j.ejpb.2025.114936

Abigail M. Poehls , Johannes M. Nitsche , Gerald B. Kasting

The existence of a storage capacity or reservoir function within human stratum corneum (HSC) for topically applied chemicals is well documented. However, the source of this reservoir remains ambiguous and may well depend on the chemical and the exposure conditions. We have investigated the role of reversible binding to keratin in contributing to this phenomenon by measuring the kinetics of uptake and desorption of solutes from isolated HSC, delipidized HSC, and silicone membrane from buffered aqueous solutions (pH 5.5) in vitro. A lipophilic permeant, geraniol, was studied for periods ranging from 24 to 168 h. Additional desorption data for testosterone and 1-propanol from isolated HSC were drawn from the literature. Results were compared with theoretical predictions for a homogeneous membrane with either no binding, equilibrium binding or slowly reversible binding. The theory includes a hitherto unpublished analysis of the short-time and long-time behavior of such systems. Calculations were also conducted for selected corticosteroids, the original stimuli for the HSC reservoir function concept. The HSC and delipidized HSC data for geraniol were most consistent with slowly reversible binding in the protein phase of the tissue. Almost complete desorption was achieved within 2–3 h of exposure to permeant-free buffer. Testosterone and 1-propanol data were consistent with this picture. Model-based calculations for corticosteroids, however, predict much longer retention times in the stratum corneum – up to two weeks – when extrapolated to the case of partially hydrated skin. We conclude that, while slowly reversible binding of many lipophilic permeants in the protein phase of the tissue is supported, the combination of very low diffusion rates in the lipid phase with strong equilibrium binding in the protein phase is a major contributor to HSC reservoir function for corticosteroids.

在人体角质层（HSC）中存在一种储存能力或储存功能，可以储存局部应用的化学品。然而，这个储层的来源仍然不明确，很可能取决于化学物质和暴露条件。我们通过测量体外缓冲水溶液（pH 5.5）中分离的HSC、去脂化的HSC和硅酮膜中溶质的摄取和解吸动力学，研究了角蛋白可逆结合在促成这一现象中的作用。一种亲脂性渗透剂，香叶醇，在24至168 h的时间内被研究。从文献中提取分离的HSC中睾酮和1-丙醇的其他解吸数据。结果比较了理论预测的均质膜要么不结合，平衡结合或缓慢可逆的结合。该理论包括迄今未发表的对此类系统的短期和长期行为的分析。还对选定的皮质类固醇进行了计算，这是HSC储库功能概念的原始刺激。香叶醇的HSC和去脂化HSC数据与组织蛋白相的缓慢可逆结合最为一致。在暴露于无渗透缓冲液的2-3 h内几乎完全解吸。睾酮和1-丙醇的数据与此相符。然而，基于模型的皮质类固醇的计算预测，在角质层中保留时间要长得多——当外推到部分水合皮肤的情况下，可达两周。我们得出的结论是，虽然许多亲脂渗透剂在组织的蛋白质相中缓慢可逆结合得到支持，但脂相中极低的扩散速率与蛋白质相中强平衡结合的结合是皮质类固醇的HSC储存库功能的主要贡献者。

{"title":"Does slowly reversible binding to keratin contribute to stratum corneum reservoir function?","authors":"Abigail M. Poehls , Johannes M. Nitsche , Gerald B. Kasting","doi":"10.1016/j.ejpb.2025.114936","DOIUrl":"10.1016/j.ejpb.2025.114936","url":null,"abstract":"<div><div>The existence of a storage capacity or reservoir function within human stratum corneum (HSC) for topically applied chemicals is well documented. However, the source of this reservoir remains ambiguous and may well depend on the chemical and the exposure conditions. We have investigated the role of reversible binding to keratin in contributing to this phenomenon by measuring the kinetics of uptake and desorption of solutes from isolated HSC, delipidized HSC, and silicone membrane from buffered aqueous solutions (pH 5.5) in vitro. A lipophilic permeant, geraniol, was studied for periods ranging from 24 to 168 h. Additional desorption data for testosterone and 1-propanol from isolated HSC were drawn from the literature. Results were compared with theoretical predictions for a homogeneous membrane with either no binding, equilibrium binding or slowly reversible binding. The theory includes a hitherto unpublished analysis of the short-time and long-time behavior of such systems. Calculations were also conducted for selected corticosteroids, the original stimuli for the HSC reservoir function concept. The HSC and delipidized HSC data for geraniol were most consistent with slowly reversible binding in the protein phase of the tissue. Almost complete desorption was achieved within 2–3 h of exposure to permeant-free buffer. Testosterone and 1-propanol data were consistent with this picture. Model-based calculations for corticosteroids, however, predict much longer retention times in the stratum corneum – up to two weeks – when extrapolated to the case of partially hydrated skin. We conclude that, while slowly reversible binding of many lipophilic permeants in the protein phase of the tissue is supported, the combination of very low diffusion rates in the lipid phase with strong equilibrium binding in the protein phase is a major contributor to HSC reservoir function for corticosteroids.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"220 ","pages":"Article 114936"},"PeriodicalIF":4.3,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0