Journal of pharmaceutical sciences最新文献_第3页

Generalized flow imaging microscopy instrument settings for measuring subvisible particle sizes and concentrations in protein therapies 用于测量蛋白质治疗中不可见颗粒大小和浓度的通用流成像显微镜仪器设置。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2026-01-23 DOI: 10.1016/j.xphs.2026.104171

Austin L. Daniels , Sushma Parab , Sigrid C. Kuebler , Soumen Das

Flow imaging microscopy (FIM) is a common imaging-based technique for measuring the subvisible particle content of protein therapies. FIM measurement accuracy strongly depends on particle segmentation, the process of detecting particles in digital images. Some FIM instruments like FlowCam allow users to adjust capture settings, parameters that influence segmentation algorithm performance. However, it has been challenging to identify settings that simultaneously yield accurate measurements of the various particle types found in protein formulations and common particle standards used for instrument qualification and validation. The present study describes generalized capture settings that allow FIM instruments to accurately measure the size and concentration of common particle types encountered in protein therapy development and manufacturing. The settings were developed using a mixture of qualitative and quantitative optimization strategies, as well as using both particle standards and representative samples. At these settings, FIM instruments yielded accurate measurements on opaque (e.g., polystyrene beads) and translucent (e.g., ethylene tetrafluoroethylene particles) particle standards. Protein formulations were also analyzed using these settings to investigate the impact of these settings on the measured subvisible particle content. These settings yield accurate measurements of typical particle types in protein formulations and aim to aid in standardizing FIM as an analytical technique.

流动成像显微镜（FIM）是一种常见的基于成像的技术，用于测量蛋白质疗法的亚可见颗粒含量。FIM测量精度在很大程度上取决于粒子分割，即数字图像中检测粒子的过程。一些FIM工具，如FlowCam，允许用户调整影响分割算法性能的捕获设置参数。然而，确定同时产生准确测量蛋白质配方中发现的各种颗粒类型和用于仪器鉴定和验证的常见颗粒标准的设置一直具有挑战性。本研究描述了广义捕获设置，允许FIM仪器准确测量蛋白质治疗开发和制造中遇到的常见颗粒类型的大小和浓度。这些设置是通过混合使用定性和定量优化策略，以及颗粒标准和代表性样本来开发的。在这些设置下，FIM仪器对不透明（如聚苯乙烯珠）和半透明（如乙烯四氟乙烯颗粒）颗粒标准进行了精确测量。还使用这些设置分析蛋白质配方，以研究这些设置对测量的亚可见颗粒含量的影响。这些设置产生蛋白质配方中典型颗粒类型的精确测量，旨在帮助将FIM作为一种分析技术进行标准化。

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引用次数: 0

Do we worry too much about polysorbate degradation? An industry-wide perspective with real-life case studies. 我们是否过于担心聚山梨酯的降解？全行业视角与现实案例研究。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2026-01-17 DOI: 10.1016/j.xphs.2026.104169

Klaus Wuchner, Felix Nikels, Patrick Garidel, Karoline Bechtold-Peters, Sanjay Gupta, Pierre Guibal, Linda Yi, Neil Steinmeyer, Cyrille Chery, Sebastian Peuker, Ryan E Mould, Shousong Jason Zhang, Charlie Bupp, Felix Wiggers, Yogita Krishnamachari, Indira Prajapati, Stefan Bleher

Polysorbates are commonly used in biotherapeutic drug formulations, but their stability over the course of the product's shelf life is a matter of concern. An industry-wide survey involving 15 biopharmaceutical companies found that 23 biotherapeutic drug products (DPs) in clinical development exhibited significant reductions in polysorbate (PS) content during long-term storage at 2-8 °C. In all cases, this decline did not impact critical quality attributes (CQAs), except for the formation of fatty acid (FA)-related sub-visible particles (SVP) in 7 DPs and FA-visible particles (VP) in 1 DP. Particle formation predominantly resulted from enzymatic or uncharacterized degradation mechanisms, not oxidative pathways. Corrective measures, such as optimization of downstream purification or reformulation, were undertaken only when SVP levels exceeded acceptable thresholds. For PS20 and PS80, the levels of FAs generated were estimated and translated into predicted SVP levels based on theoretical assumptions. Additionally, the current understanding of PS degradation in biopharmaceuticals, based on the latest literature, is summarized, with consideration of safety and immunogenicity aspects related to the primary PS degradation products. Overall, PS degradation is considered manageable and not problematic under practical conditions. Enzymatic hydrolysis of PS is generally deemed acceptable, provided that all CQAs are maintained within specified limits. If FA-related particles are formed it is recommended that the PS degradation pathway is well characterized, and an appropriate control strategy be implemented.

聚山梨酯通常用于生物治疗药物配方，但其在产品保质期内的稳定性是一个值得关注的问题。一项涉及15家生物制药公司的全行业调查发现，在2-8 °C的长期储存中，临床开发的23种生物治疗药物（DPs）的聚山梨酸酯（PS）含量显著降低。在所有情况下，这种下降都没有影响关键质量属性（cqa），除了在7个DP中形成脂肪酸（FA）相关的亚可见颗粒（SVP）和在1个DP中形成FA可见颗粒（VP）。颗粒的形成主要是由于酶或未表征的降解机制，而不是氧化途径。只有当SVP水平超过可接受阈值时，才采取纠正措施，如优化下游净化或重新配方。对于PS20和PS80，根据理论假设估计产生的FAs水平并将其转化为预测的SVP水平。此外，基于最新文献，总结了目前对生物制药中PS降解的认识，并考虑了与主要PS降解产物相关的安全性和免疫原性方面。总的来说，PS退化被认为是可控的，在实际条件下没有问题。PS的酶解通常被认为是可以接受的，只要所有的cqa保持在规定的范围内。如果形成fa相关颗粒，则建议对PS降解途径进行充分表征，并采取适当的控制策略。

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引用次数: 0

Control strategy for subvisible particulates of therapeutic protein injections in pre-filled syringes using flow imaging 利用流动成像技术对预充式注射器中治疗性蛋白注射的亚可见颗粒进行控制。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2026-01-16 DOI: 10.1016/j.xphs.2026.104168

Bin Zhang , Katiria Flores , Nathyn Horvath , Nidia Gonzalez Lopez , Nishant Sawant , Eric Falcone , Stanley C. Kwok , Shalini Minocha , Vinay Radhakrishnan

Pre-filled syringes (PFSs) are a widely used container closure for therapeutic protein injections, enabling simplified preparation and at-home administration. PFSs are commonly lubricated with sprayed-on silicone oil (SiO), which may migrate into drug product as SiO particles during storage and transportation. Elevated subvisible particle (SVP) counts from SiO present challenges for meeting USP 〈788〉 specification and may raise potential immunogenicity and toxicity risks. Light Obscuration (LO), the primary compendial method for PFS product release and stability testing, cannot differentiate SiO SVPs from proteinaceous SVPs. This drives the need for more comprehensive SVP characterization approaches for PFS products. Microflow Imaging (MFI) measures SVP count, size distributions, morphology and could differentiate fibrillar and translucent proteinaceous SVPs from spherical SiO SVPs using a morphological Aspect Ratio (AR) < 0.85 filter. This manuscript proposes a SVP control strategy for PFS products using MFI, supported by data demonstrating sensitivity to particle detection and stability-indicating capability. Additional data from orthogonal FlowCam (for counts) and complementary Raman Microscopy (for SiO identification) are presented. For Protein X, MFI was tested on multiple lots and shown as effective characterization tool to develop a product-specific control strategy. The proposed SVP control strategy holds considerable promise to assess and control SVP for injectable drug products.

预充式注射器（pfs）是一种广泛用于治疗性蛋白质注射的封闭容器，可以简化制备和在家给药。pfs通常使用喷淋硅油（SiO）润滑，在储存和运输过程中，硅油可能以SiO颗粒的形式迁移到药品中。SiO中亚可见颗粒（SVP）计数升高对符合USP规范提出了挑战，并可能增加潜在的免疫原性和毒性风险。光遮蔽（LO）， PFS产品释放和稳定性测试的主要药典方法，不能区分SiO svp和蛋白svp。这推动了对PFS产品更全面的SVP表征方法的需求。微流成像（Microflow Imaging， MFI）可以测量SVP的数量、大小分布、形态，并使用形态宽高比(AR) < 0.85的滤光片将纤维状和半透明蛋白状SVP与球形SiO SVP区分开来。本文提出了一种使用MFI的PFS产品的SVP控制策略，并提供了对颗粒检测的敏感性和稳定性指示能力的数据支持。另外的数据从正交流量凸轮（计数）和互补拉曼显微镜（硅氧化物鉴定）提出。对于蛋白质X， MFI在多个批次上进行了测试，并被证明是开发产品特定控制策略的有效表征工具。建议的SVP控制策略对评估和控制注射药品SVP具有相当大的希望。

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引用次数: 0

A comprehensive discussion on analytical method development and validation of a USP type-IV dissolution method for dexamethasone in a combination ophthalmic suspension with povidone-iodine 对复方聚维酮碘眼用混悬液中地塞米松溶出度分析方法开发和验证的综合讨论。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2026-01-15 DOI: 10.1016/j.xphs.2026.104165

Likhit Mandal , Dr. Praveen Kumar Vemuri

Antimicrobial resistance resulting from the widespread use of topical antibiotics has accelerated the need for non-antibiotic strategies in ocular therapy. Povidone-iodine (PVP-I) offers broad antimicrobial activity without inducing resistance, while dexamethasone provides potent anti-inflammatory effects, making their combination a promising ophthalmic suspension for infectious and inflammatory conditions. To ensure therapeutic consistency, in-vitro dissolution testing is critical for suspension of Dexamethasone, as it characterizes drug release, supports formulation optimization, and provides evidence for regulatory bio-waivers. This investigation was carried out to develop and validate a USP Type-IV flow-through cell method (closed-loop configuration) for assessing the in-vitro release behavior of dexamethasone (0.1%) from povidone-iodine (0.6%) and dexamethasone (0.1%) ophthalmic suspension. The current dissolution method employed phosphate buffer (pH 7.4) with 0.1% β-cyclodextrin as medium, chosen for solubility, stability, and sink condition. A 100 kDa cellulose ester membrane enabled controlled diffusion. Chromatographic separation was performed on an ACE Excel-5 C8 column (250 × 4.6 mm, 5 µm) using an isocratic mobile phase of 0.6% β-cyclodextrin in water and acetonitrile (1:1 v/v). Partial validation per ICH Q2(R2) confirmed excellent linearity (r² > 0.999), precision (%RSD < 2.0), accuracy (98.5–101.5%), and solution stability for 72 h. The method was discriminatory for formulation changes and suitable for routine and stability testing of ophthalmic suspensions.

广泛使用局部抗生素导致的抗菌素耐药性加速了对非抗生素治疗策略的需求。聚维酮-碘（PVP-I）具有广泛的抗菌活性而不会引起耐药性，而地塞米松具有有效的抗炎作用，使它们的组合成为治疗感染性和炎症性疾病的有前途的眼用悬浮液。为了确保治疗的一致性，体外溶出度测试对地塞米松悬浊液至关重要，因为它表征药物释放，支持配方优化，并为监管生物豁免提供证据。本研究旨在建立并验证USP iv型流式细胞法（闭环配置），用于评估聚维酮碘（0.6%）和地塞米松（0.1%）眼用混悬液中地塞米松（0.1%）的体外释放行为。目前的溶出方法采用磷酸缓冲液（pH 7.4）， 0.1% β-环糊精为介质，选择溶解度、稳定性和沉淀条件。一个100kda的纤维素酯膜可以控制扩散。色谱柱为ACE Excel-5 C8(250 × 4.6 mm, 5µm)，流动相为0.6% β-环糊精-水-乙腈（1:1 v/v）。根据ICH Q2（R2）进行的部分验证证实，该方法具有良好的线性（r²> 0.999）、精密度（%RSD < 2.0）、准确度（98.5-101.5%）和72 h的溶液稳定性。该方法对处方变化具有判别性，适用于眼科混悬液的常规和稳定性检测。

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引用次数: 0

Long-acting delivery of a model monoclonal antibody from ethylene vinyl acetate implants at a high loading: Drug release and protein stability 高负荷醋酸乙烯酯植入物模型单克隆抗体的长效递送：药物释放和蛋白质稳定性。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2026-01-15 DOI: 10.1016/j.xphs.2026.104167

Yu Tong Tam , Harsh Patel , Jeffrey C. Haley , Alexander Dimmling , Devin B. Tesar , Alavattam Sreedhara

Delivering large therapeutic monoclonal antibodies (mAbs) from solid polymer matrices via hot-melt extrusion (HME) is a promising approach to achieving a prolonged release profile. However, this approach presents significant challenges due to protein instability under high temperatures and high shear forces typically involved in the extrusion process and during extended-release duration in physiological conditions. Herein, we discuss the encapsulation of a large therapeutic mAb (MW ∼150 kDa) at a high loading (≥50%) via HME and vacuum compression molding (VCM) with ethylene vinyl acetate (EVA) and its stability analysis upon release from EVA rods. Protein stability of a model mAb (mAb1) with respect to protein aggregation, structural stability, and relative binding activity was evaluated. A solid spray-dried formulation of mAb1 can maintain its protein stability against elevated temperature and repeated heating cycles during the manufacturing process with EVA. In the present work, we show that applying a second thermal step via VCM can enable a homogeneous distribution of solid spray-dried particles of mAb1 embedded within the solid EVA matrix. Additionally, our results demonstrate that implementing a membrane coating on EVA rods can yield a slow release of mAb1 from EVA rods without significantly impacting protein stability, representing a viable approach for the long-acting delivery of mAbs using EVA as a non-biodegradable polymer implant.

通过热熔挤压（HME）从固体聚合物基质中输送大剂量治疗性单克隆抗体（mab）是一种很有前途的方法，可以实现长时间的释放。然而，这种方法面临着巨大的挑战，因为在高温和高剪切力下，蛋白质不稳定通常涉及挤压过程和生理条件下的延长释放时间。在此，我们讨论了通过HME和真空压缩成型（VCM）与醋酸乙烯（EVA）在高负荷（≥50%）下对大型治疗性单抗（MW ~ 150 kDa）的封装，以及其从EVA棒释放后的稳定性分析。从蛋白质聚集、结构稳定性和相对结合活性方面对模型mAb （mAb1）的蛋白质稳定性进行了评估。固体喷雾干燥制剂mAb1可以在EVA制造过程中保持其蛋白质稳定性，抵抗高温和反复加热循环。在目前的工作中，我们表明通过VCM应用第二热步骤可以使嵌入在固体EVA矩阵中的固体喷雾干燥的mAb1颗粒均匀分布。此外，我们的研究结果表明，在EVA棒上实施膜涂层可以使mAb1从EVA棒中缓慢释放，而不会显著影响蛋白质的稳定性，这代表了使用EVA作为不可生物降解的聚合物植入物长期递送mAb1的可行方法。

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引用次数: 0

Analysis of the formation of (sub)visual particles in ready-to-administer trastuzumab infusion bags during transport from the hospital pharmacy to patients at home 曲妥珠单抗输注袋在从医院药房运送到患者家中的过程中形成（亚）视觉颗粒的分析

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2026-01-14 DOI: 10.1016/j.xphs.2026.104164

Charlotte Sikking , T.Ton Dinh , Mirjam Crul , Stefan G. Romeijn , Charlotte van Kesteren , Marieke M. Beex-Oosterhuis

For biological drugs, subvisible particle formation can cause loss of efficacy of the drug or trigger immune reactions. Transport of ready-to-administer infusion bags, to enable home treatment of cancer patients, might cause particle formation. The primary aim of this observational prospective pharmaceutical study is to investigate the effect of transport by car on the formation of subvisible particles in ready-to-administer infusion bags with trastuzumab. Hereto, trastuzumab was compounded (n = 19 infusion bags) in the hospital pharmacy and transported by car to patients’ homes and thereafter to the laboratory for analysis. The analysis comprised visual inspection and qualitative and quantitative analyses of particle formation. The key findings revealed no significant difference in amount of particles between transported and non-transported bags based on the FlowCam, nanoparticle and HP-SEC analyses. Light obscuration revealed a statistically significant lower amount of particles ≥10 μm in non-transported samples, although absolute numbers of these particles was low. Transporting reconstituted trastuzumab infusion bags by car does not lead to a significant increase in the amount of aggregates in the infusion bags. Therefore, with regards to particle formation, home treatment of patients with trastuzumab was safe.

对于生物药物，不可见颗粒的形成会导致药物药效丧失或引发免疫反应。为使癌症患者能够在家中治疗而运输即用输液袋，可能会导致颗粒形成。这项观察性前瞻性药物研究的主要目的是研究汽车运输对曲妥珠单抗输注袋中亚可见颗粒形成的影响。在本研究中，曲妥珠单抗在医院药房配药（n=19个输液袋），然后由汽车运送到患者家中，然后送到实验室进行分析。分析包括目视检查和颗粒形成的定性和定量分析。根据FlowCam、纳米颗粒和HP-SEC分析，主要发现运输和非运输袋之间的颗粒数量没有显着差异。在光线遮挡下，非运输样品中≥10 μm的颗粒数量明显减少，尽管这些颗粒的绝对数量很低。用汽车运输重组曲妥珠单抗输液袋不会导致输液袋中不可见颗粒的数量显著增加，因此曲妥珠单抗患者的家庭治疗是安全的。

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引用次数: 0

Ionic strength mitigates solvent/detergent–induced tertiary expansion of hemopexin 离子强度减轻溶剂/清洁剂引起的血凝素三级膨胀。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2026-01-14 DOI: 10.1016/j.xphs.2026.104166

Min-Jung Kim , Jaeeun Jung , Jieun Kang , Nohra Park , Sung Jun Lee , Geunhye Yeo , Sangho Lee

Hemopexin (Hx) is a plasma glycoprotein that scavenges free heme with sub-nanomolar affinity and under development as a therapeutic. Solvent/detergent treatment (S/D) is routinely applied to plasma-derived manufacturing for viral safety and generally considered non-disruptive. However, the histidine- and aromatic residue-rich heme pocket at the inter-domain interface may render Hx susceptible to S/D. We investigated whether S/D perturbs the tertiary structure of Hx and elevated ionic strength mitigates such effects. Changes in the apparent size and activity of Hx exposed to S/D were assessed by size-exclusion HPLC (SE-HPLC) and functional assays. S/D consistently reduced activity and shifted SE-HPLC profiles toward a larger hydrodynamic size. Small-angle X-ray scattering (SAXS) revealed expansion of the molecular envelope of Hx by S/D, suggesting that the heme pocket may initiate hinge relaxation between two β-propeller domains of Hx. To mitigate such expansion by S/D, we screened a formulation range of NaCl concentration. Increasing ionic strength compacted SAXS profiles toward the native state and restored activity, consistent with pocket stabilization by charge. These findings identify Hx as an exception to typical S/D tolerance and demonstrate that modulation of ionic strength represents an effective strategy to preserve structural integrity and function while fulfilling viral safety requirements.

血红素（Hx）是一种血浆糖蛋白，具有亚纳摩尔亲和力，可以清除游离血红素，目前正在开发中。溶剂/洗涤剂处理（S/D）通常用于血浆源性生产，以确保病毒安全，通常被认为是无破坏性的。然而，域间界面上富含组氨酸和芳香残基的血红素口袋可能使Hx对S/D敏感。我们研究了S/D是否扰乱了Hx的三级结构，而离子强度的提高减轻了这种影响。采用粒径排除高效液相色谱法（SE-HPLC）和功能测定法评估S/D作用下Hx的表观大小和活性变化。S/D持续降低活性，并将SE-HPLC图谱转向更大的水动力尺寸。小角x射线散射（SAXS）显示Hx的分子包膜以S/D扩展，表明血红素口袋可能引发Hx两个β-螺旋桨结构域之间的铰链松弛。为了通过S/D抑制这种膨胀，我们筛选了一个NaCl浓度的配方范围。离子强度的增加使SAXS曲线向原生状态靠拢，并恢复了活性，这与电荷稳定袋相一致。这些发现表明Hx是典型S/D耐受性的例外，并表明离子强度的调节是在满足病毒安全要求的同时保持结构完整性和功能的有效策略。

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引用次数: 0

A novel bicyclic peptide-drug conjugate of 3-fluoro-10-hydroxy-evodiamine for targeted colorectal cancer therapy. 一种用于结直肠癌靶向治疗的新型3-氟-10-羟基- evolodiamine双环肽-药物偶联物。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2026-01-13 DOI: 10.1016/j.xphs.2026.104160

Siyuan Zhao, Chang Chu, Cuiping Li, Qiaoli Zhai, Juan Liu, Huan Sun, Xin Wu, Kourong Shi, Wei Fan

This study aimed to develop a novel peptide-drug conjugate (PDC) by conjugating 3-fluoro-10-hydroxy-evodiamine (FOE) with a bicyclic peptide (BiP) targeting the EphA2 receptor. The goal was to enhance the solubility, tumor selectivity, and therapeutic efficacy of FOE against colorectal cancer (CRC). FOE and BiP were chemically synthesized and coupled through a valine-citrulline cleavable linker to generate BiP-FOE. The compound was structurally characterized, and its solubility, plasma stability, and in vitro cytotoxicity were evaluated in CRC cells. Its effects on cell migration, invasion, apoptosis, and the cell cycle were also assessed. The in vivo targeting ability, antitumor efficacy, and safety were evaluated in an HCT116 xenograft mouse model. BiP-FOE exhibited a greater than 200-fold improvement in aqueous solubility and good metabolic stability. In vitro, BiP-FOE showed selective and potent cytotoxicity toward EphA2-positive HCT116 cells, significantly inhibiting migration and invasion while inducing S-phase arrest and apoptosis. In vivo, BiP-FOE achieved significant accumulation at the tumor site and effectively suppressed tumor growth, with efficacy comparable to or exceeding that of 5-FU. It demonstrated a favorable safety profile, showing minimal body weight loss, negligible hemolysis, and no detectable organ toxicity. BiP-FOE successfully combines the cytotoxic potential of FOE with the tumor-targeting capacity of a bicyclic peptide, resulting in improved solubility, selectivity, efficacy, and safety. These findings highlight BiP-FOE as a promising candidate for targeted CRC therapy and warrant further preclinical development.

本研究旨在通过3-氟-10-羟基- evolodiamine （FOE）与一种靶向EphA2受体的双环肽（BiP）偶联，开发一种新型肽-药物偶联物（PDC）。目的是提高FOE对结直肠癌（CRC）的溶解度、肿瘤选择性和治疗效果。采用化学方法合成FOE和BiP，并通过缬氨酸-瓜氨酸可切割连接体偶联生成BiP-FOE。对该化合物进行了结构表征，并对其在结直肠癌细胞中的溶解度、血浆稳定性和体外细胞毒性进行了评价。评估其对细胞迁移、侵袭、凋亡和细胞周期的影响。在HCT116异种移植小鼠模型中评估其体内靶向能力、抗肿瘤功效和安全性。BiP-FOE表现出200倍以上的水溶性改善和良好的代谢稳定性。在体外，BiP-FOE对epha2阳性的HCT116细胞表现出选择性和强效的细胞毒性，显著抑制迁移和侵袭，诱导s期阻滞和凋亡。在体内，BiP-FOE在肿瘤部位显著蓄积，有效抑制肿瘤生长，其疗效与5-FU相当或超过5-FU。它显示出良好的安全性，表现出最小的体重减轻，可忽略的溶血，没有可检测到的器官毒性。BiP-FOE成功地将FOE的细胞毒性潜能与双环肽的肿瘤靶向能力结合起来，从而提高了溶解度、选择性、有效性和安全性。这些发现突出了BiP-FOE作为靶向CRC治疗的有希望的候选药物，值得进一步的临床前开发。

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引用次数: 0

Investigating the SNAC-to-drug ratio for the oral absorption of cyanocobalamin in rats 研究大鼠口服氰钴胺素吸收的snc -药比。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2026-01-13 DOI: 10.1016/j.xphs.2026.104163

Po-Chang Chiang , Jia Liu , Karthik Nagapudi , Jodie Pang , Emile Plise , Michael Dolton , Matthew R. Durk

The oral route of administration continues to be the preferred and most convenient method for drug delivery among both patients and healthcare professionals. This preference is based not only on its user-friendliness but also on the practicality it provides regarding formulation flexibility and dosage adjustability. Nevertheless, the effectiveness of oral drug delivery is significantly influenced by the ADME (Absorption, Distribution, Metabolism, and Excretion) characteristics of the drug. Among these characteristics, permeability is a key factor affecting oral bioavailability, making the exploration of permeability enhancers a vital research focus to boost oral absorption. Recent investigations have highlighted sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC) as a promising permeability enhancer, demonstrating its potential to increase the absorption rates of various substances. Despite its proven effectiveness, the precise mechanisms by which SNAC promotes this enhancement are not yet fully understood. Furthermore, the specific dosage of SNAC required to improve drug absorption remains unclear. This study aims to examine the dose-dependent effects of SNAC on the model compound cyanocobalamin (Vitamin B12) in rats. The in vivo findings were integrated with modeling and simulation to determine the critical concentration of SNAC and the minimum molar ratio, and the overall enhancement effect at various SNAC concentrations for cyanocobalamin needed to achieve permeation enhancement. This knowledge could assist formulators in more effectively incorporating SNAC into formulations for enhanced therapeutic outcomes.

口服给药途径仍然是患者和医疗保健专业人员首选和最方便的给药方法。这种偏好不仅基于它的用户友好性，而且基于它在配方灵活性和剂量可调节性方面提供的实用性。然而，口服给药的有效性受到药物的ADME（吸收、分布、代谢和排泄）特性的显著影响。其中，渗透性是影响口服生物利用度的关键因素，因此探索渗透性增强剂是促进口服吸收的重要研究热点。最近的研究强调了N-[8-（2-羟基苯甲酰）氨基]辛酸钠（SNAC）作为一种有前途的渗透性增强剂，表明它有可能提高各种物质的吸收率。尽管SNAC已被证明有效，但其促进这种增强的确切机制尚不完全清楚。此外，SNAC改善药物吸收所需的具体剂量尚不清楚。本研究旨在探讨SNAC对大鼠模型化合物氰钴胺素（维生素B12）的剂量依赖性作用。将体内实验结果与模型和模拟相结合，确定SNAC的临界浓度和最小摩尔比，以及不同SNAC浓度下氰钴胺素达到渗透增强所需的总体增强效果。这些知识可以帮助配方师更有效地将SNAC纳入配方中，以提高治疗效果。

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引用次数: 0

Continuous lyophilization of suspended vials with per-vial inline analytics 连续冻干悬浮小瓶与每瓶在线分析。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2026-01-10 DOI: 10.1016/j.xphs.2026.104157

Bernhardt L. Trout , Steven J. Burcat , Rohan P. Kadambi , Lorenzo J. Stratta , Richard D. Braatz , Roberto Pisano , Alexander H. Slocum

Pharmaceutical lyophilization (vacuum freeze-drying) removes water from aqueous drug products to stabilize formulations. This work presents a continuous final-dose pharmaceutical lyophilizer that can integrate with continuous production chains, increasing process quality, speed, and flexibility. Performance is assessed by freeze-drying various model formulations, and the cakes produced showed no visual defects, low residual moisture, and no loss in bioactivity. Moreover, this system moves vials via magnetic levitation and includes process analytical technologies (PAT) to monitor the sublimation rate and temperature of every vial in the system, enabling the possibility of real time release and model-based feedback control to optimize drying conditions. The modular design of this continuous lyophilizer provides a direct link between laboratory and production-scale equipment, greatly simplifying the scale-up difficulty found in the traditional batch process.

药品冻干（真空冷冻干燥）从含水药品中除去水分以稳定制剂。这项工作提出了一种连续的最终剂量药物冻干机，可以与连续生产链集成，提高工艺质量，速度和灵活性。通过冷冻干燥各种模型配方来评估性能，生产的蛋糕没有视觉缺陷，残留水分低，生物活性没有损失。此外，该系统通过磁悬浮移动小瓶，并包括过程分析技术（PAT）来监测系统中每个小瓶的升华速率和温度，从而实现实时释放和基于模型的反馈控制，以优化干燥条件。这种连续冻干机的模块化设计提供了实验室和生产规模设备之间的直接联系，大大简化了传统批处理过程中发现的放大难度。

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