Journal of pharmaceutical sciences最新文献_第6页

Photodegradation of dacarbazine irradiated by common lighting sources: An examination of the differences between light-emitting diode (LED) and fluorescent light 普通光源照射下达卡巴嗪的光降解：发光二极管（LED）和荧光灯之间差异的检验。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2025-12-26 DOI: 10.1016/j.xphs.2025.104148

Shun Takayama , Yukiko Nagai , Tomomi Sugiyama , Fumiyuki Ito , Jun Miyazaki

Light-sensitive pharmaceuticals are susceptible to alteration or degradation under ambient light conditions, such as sunlight or artificial lighting, requiring pharmacists and patients to prevent exposure of these drugs to light. However, the transition from fluorescent to light-emitting diode (LED) light has altered the ambient light characteristics within buildings. Dacarbazine, chemically known as 5-(3,3-dimethyl-1-triazen-1-yl)-1H-imidazole-4-carboxamide (DTIC), is a light-sensitive anticancer drug. Its photodegradation product, Diazo-IC (5-diazoimidazole-4-carboxamide) is known to cause vascular pain in patients during infusion. Utilizing UV/Vis spectroscopy, this study examines the photodegradation of DTIC in aqueous solution under fluorescent and light-emitting diode (LED) lighting conditions, which are both prevalent in contemporary buildings. Results indicate that DTIC remained stable when exposed to LED light, with no decomposition observed, whereas photodegradation occurred under fluorescent light. The residual ratio revealed that DTIC remained stable for 240 min under LED illumination, indicating that LED light exposure does not induce DTIC photodegradation. These findings suggest that the ongoing replacement of fluorescent lighting with LED in healthcare settings and patient residences may eliminate vascular pain associated with DTIC photodegradation in the near future.

光敏药物在环境光条件下容易发生变化或降解，例如阳光或人工照明，这要求药剂师和患者防止将这些药物暴露在光线下。然而，从荧光灯到发光二极管（LED）的转变已经改变了建筑物内的环境光特性。达卡巴嗪，化学上被称为5-（3,3-二甲基-1-三氮基）-咪唑-4-羧酰胺（DTIC），是一种光敏抗癌药物。其光降解产物Diazo-IC（5-重氮咪唑-4-carboxamide）在输注过程中引起血管疼痛。利用紫外/可见光谱学，本研究考察了在荧光和发光二极管（LED）照明条件下水溶液中DTIC的光降解情况，这两种照明条件在当代建筑中都很普遍。结果表明，DTIC在LED光下保持稳定，未发生分解，而在荧光灯下发生光降解。残留比表明，在LED照射下，DTIC在240 min内保持稳定，表明LED光照射不会导致DTIC光降解。这些发现表明，在不久的将来，在医疗机构和病人住所用LED代替荧光灯可能会消除与DTIC光降解相关的血管疼痛。

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引用次数: 0

Design and synthesis of carbamate-linked ester prodrugs selectively activated by carboxylesterase 1 with enhanced stability against intestinal hydrolysis 羧酸酯酶1选择性激活氨基甲酸酯前药的设计与合成，增强了抗肠道水解的稳定性。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2025-12-25 DOI: 10.1016/j.xphs.2025.104146

Masato Takahashi, Shintaro Sakamoto, Nao Sakamoto, Sora Nishimura, Seonho Hwang, Jihyun Kim, Masakiyo Hosokawa

Ester-based prodrugs are often prematurely hydrolyzed by intestinal carboxylesterases, leading to reduced bioavailability and potential gastrointestinal (GI) toxicity. To overcome this limitation, a series of diester, carbonate-linked ester, and carbamate-linked ester prodrugs were synthesized and evaluated using human liver microsomes (HLM), human intestinal microsomes (HIM), and recombinant carboxylesterases (CES1A1 and CES2A1). Under strongly acidic conditions (pH 1.2), all prodrugs remained highly stable (>98% remaining after 6 h). In human plasma, however, diester prodrugs showed relatively rapid degradation (approximately 50% remaining after 6 h), whereas carbonate- and carbamate-linked esters displayed enhanced stability. Diester and carbonate-linked ester prodrugs were hydrolyzed by both HLM and HIM, indicating non-selective activation. By contrast, several carbamate-linked ester prodrugs showed high HLM/HIM selectivity, with CES1A1/CES2A1 hydrolysis rate ratios exceeding 50. Docking simulations showed favorable active-site binding of carbamate-linked ester prodrugs to CES1A1 but not to CES2A1, supporting the selectivity of CES1A1. These findings suggest that carbamate-based prodrug strategies can be employed to improve intestinal stability and enable controlled systemic activation, potentially reducing off-target effects and enhancing oral drug delivery. This strategy may also be applicable to liver- or lung-targeted prodrug design.

以酯为基础的前药经常被肠道羧酸酯酶过早水解，导致生物利用度降低和潜在的胃肠道毒性。为了克服这一局限性，我们利用人肝微粒体（HLM）、人肠微粒体（HIM）和重组羧酸酯酶（CES1A1和CES2A1）合成了一系列双酯、碳酸酯连接酯和氨基甲酸酯连接酯前药，并对其进行了评价。在强酸性条件下（pH 1.2），所有前药均保持高度稳定（6 h后仍保持bb0.98%）。然而，在人血浆中，二酯前药表现出相对较快的降解（6小时后约有50%残留），而碳酸盐和氨基甲酸酯连接的酯则表现出更高的稳定性。双酯和碳酸酯连接的前药均被HLM和HIM水解，表明非选择性活化。相比之下，几种氨基甲酸酯连接酯前药表现出较高的HLM/HIM选择性，CES1A1/CES2A1水解率比超过50。对接模拟显示，氨基甲酸酯连接酯前药与CES1A1的活性位点结合良好，而与CES2A1的活性位点结合不佳，支持CES1A1的选择性。这些发现表明，基于氨基甲酸酯的前药策略可用于改善肠道稳定性，实现受控的全身激活，潜在地减少脱靶效应并增强口服药物给药。这一策略也可能适用于肝或肺靶向前药设计。

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引用次数: 0

Challenges in surfactant removal from biopharmaceutical formulations using tangential flow filtration (TFF) and spin columns 使用TFF和自旋柱从生物制药配方中去除表面活性剂的挑战。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2025-12-25 DOI: 10.1016/j.xphs.2025.104141

Kristian Le Vay, Benjamin Steinborn, Constanze Helbig, Andrea Arsiccio, Maksymilian M. Zegota, Christa von der Schulenburg, Angelika Reichel, Tim Menzen, Andrea Hawe

Surfactants such as polysorbate 20 (PS20), polysorbate 80 (PS80), and poloxamer 188 (P188) are integral to the stabilization of protein therapeutics, yet their removal is often required during formulation development and analytical characterization. This work investigates the efficiency of surfactant removal by commercial spin columns and tangential flow filtration (TFF), using liquid chromatography with charged aerosol detection (LC-CAD) to evaluate subspecies specific behavior. Spin column experiments demonstrated effective PS20 clearance from monoclonal antibody formulations, while PS80 removal was limited, particularly for PS80 polyester species. TFF enabled selective removal of unesterified and monoester species for both polysorbates, with PS20 showing the highest overall clearance, especially when processed below its critical micelle concentration (CMC). PS80 removal was ineffective again due to retention of polyester species, while P188 exhibited slower and incomplete removal kinetics. These findings underscore the need for improved surfactant removal strategies and the importance of subspecies profile analysis in surfactant quantification.

表面活性剂如聚山梨酸酯20 （PS20）、聚山梨酸酯80 （PS80）和poloxamer 188 （P188）是蛋白质治疗药物稳定的组成部分，但在配方开发和分析表征过程中通常需要去除它们。本研究研究了商用自旋柱和切向流过滤（TFF）去除表面活性剂的效率，并使用带电荷气溶胶检测的液相色谱（LC-CAD）来评估亚种的特异性行为。自旋柱实验证明了单克隆抗体配方对PS20的有效清除，而对PS80的去除是有限的，特别是对PS80聚酯物种。TFF能够选择性去除两种聚山梨酸酯的未酯化和单酯种类，PS20显示出最高的总清除率，特别是当处理低于其临界胶束浓度（CMC）时。由于聚酯种类的保留，PS80的去除再次无效，而P188表现出较慢和不完全的去除动力学。这些发现强调了改进表面活性剂去除策略的必要性以及亚种谱分析在表面活性剂定量中的重要性。

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引用次数: 0

Large language models in drug delivery: A review of the current landscape and future perspectives 药物传递中的大型语言模型：现状和未来展望的回顾。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2025-12-24 DOI: 10.1016/j.xphs.2025.104147

Molham Sakkal , Abdallah Abou Hajal

The development of effective drug delivery systems (DDS) faces persistent challenges, including biological barriers, formulation stability, low bioavailability, and complex regulatory demands. While artificial intelligence (AI) and machine learning (ML) have gained traction in pharmaceutical research, the role of large language models (LLMs) in DDS design and development remains an emerging and underexplored area. This review provides a structured overview of the intersection between LLMs and pharmaceutical formulation. It introduces the foundational principles of LLMs, frames key formulation challenges within drug delivery, and critically examines how existing LLM-powered tools are being applied to literature mining, protocol generation, molecular property prediction, and preformulation guidance. Practical examples from recent studies are discussed to illustrate potential use cases.

We further identify key limitations in current LLM integration, including the lack of domain-specific models, limited data accessibility, risks of hallucinated outputs, and usability challenges for non-specialists. Finally, we propose essential future research directions to bridge these gaps and enhance real-world applicability. This review equips pharmaceutical scientists, formulation researchers, and interdisciplinary R&D teams with critical insights to support the responsible adoption of LLMs, ultimately accelerating the development of personalized and efficient drug delivery solutions.

开发有效的给药系统（DDS）面临着持续的挑战，包括生物屏障、配方稳定性、低生物利用度和复杂的监管要求。虽然人工智能（AI）和机器学习（ML）在制药研究中获得了牵引力，但大型语言模型（llm）在DDS设计和开发中的作用仍然是一个新兴且未充分开发的领域。这篇综述提供了法学硕士和药物制剂之间交叉的结构化概述。它介绍了法学硕士的基本原理，框架药物输送中的关键配方挑战，并批判性地检查了现有的法学硕士支持的工具如何应用于文献挖掘，协议生成，分子性质预测和配方预指导。本文讨论了来自最近研究的实际示例，以说明潜在的用例。我们进一步确定了当前LLM集成的关键限制，包括缺乏特定领域的模型，有限的数据可访问性，幻觉输出的风险以及非专业人员的可用性挑战。最后，我们提出了未来重要的研究方向，以弥合这些差距并增强现实世界的适用性。这篇综述为制药科学家、配方研究人员和跨学科研发团队提供了重要的见解，以支持负责任地采用法学硕士，最终加速个性化和高效给药解决方案的开发。

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引用次数: 0

Editorial Advisory Board 编辑顾问委员会

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2025-12-24 DOI: 10.1016/S0022-3549(25)00577-5

引用次数: 0

Forging certainty: A novel framework for the specification of combination products 锻造确定性：组合产品规范的新框架。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2025-12-24 DOI: 10.1016/j.xphs.2025.104145

Rafeek F. Shokry

The specification for a combination product represents a critical covenant of its quality. Too often, the current intellectual framework for forging this covenant remains a fragmented patchwork of legacy pharmaceutical and medical device paradigms. This paper argues that significant product failures are not random accidents but predictable consequences of these historical limitations. We therefore propose a novel, deductive framework—Quality by Design in Specification (QbD-S)—that complements existing empirical methods to address this systemic challenge. This paper presents a formal intellectual engine, the Universal Attribute Generator (UAG), which deconstructs therapeutic failure into five foundational Tenets and uses a rigorous "Interrogatory Filter" (Stress > Capacity) to systematically derive a comprehensive set of quality attributes. This framework introduces the Criticality Vector to contextualize consequence by adding the dimension of "Context" to the standard scalar of "Severity," and mandates a Structured Falsification Protocol to build scientific confidence in its conclusions. The ultimate output is a "Master Control Strategy"—a binding regulatory mandate that legislates the "Fate" of each attribute, enabling either "Input-Controlled" Real-Time Release or mandating traditional "Symptom-Controlled" testing. QbD-S provides a systematic engine for translating patient needs into a scientifically rigorous and defensible covenant of quality.

组合产品的规格代表了其质量的关键契约。目前形成这一契约的知识框架往往仍然是遗留药品和医疗器械范例的支离破碎的拼凑。本文认为，重大产品故障不是随机事故，而是这些历史限制的可预测后果。因此，我们提出了一个新颖的演绎框架——规范设计质量（QbD-S）——它补充了现有的经验方法来解决这一系统性挑战。本文提出了一个正式的智能引擎，通用属性生成器（UAG），它将治疗失败解构为五个基本原则，并使用严格的“询问过滤器”（Stress > Capacity）系统地推导出一套全面的质量属性。该框架通过将“上下文”维度添加到“严重性”的标准标量中，引入临界向量来将结果置于上下文环境中，并强制要求结构化证伪协议在其结论中建立科学信心。最终的输出是一个“主控制策略”——一个有约束力的管理命令，它规定了每个属性的“命运”，支持“输入控制”的实时发布或强制执行传统的“症状控制”测试。QbD-S提供了一个系统的引擎，将患者的需求转化为科学严谨和可辩护的质量契约。

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引用次数: 0

New method for adsorbing the pharmaceuticals on mesoporous silica: Adsorption behavior of ibuprofen on mesoporous silica via the sealed and heating method 介孔二氧化硅吸附药物的新方法：密封加热法对布洛芬在介孔二氧化硅上的吸附行为。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2025-12-24 DOI: 10.1016/j.xphs.2025.104140

Yayoi Kawano , Kazuya Nomura , Nobuyuki Natori , Takuma Oba , Chihiro Ozawa , Kaoru Hirose , Takehisa Hanawa

Many active pharmaceutical ingredients (APIs) currently being developed are poorly soluble in water, which enhances their solubility and bioavailability critical challenges. The evaporation/condensation (EV) method, wherein crystalline APIs are dissolved in organic solvents and adsorbed onto porous materials, is used to improve the solubility of APIs. However, the use of residual organic solvents during evaporation is challenging. Recently, the sealed heating (SH) method, in which a mixture of porous materials and a sublimated API is heated in a sealed container, has been reported as an alternative to the EV method. This study focuses on mesoporous silica (MPS-4R or -2R) as a porous material. The SH method was used to investigate the adsorption of ibuprofen (IBU) on MPSs. In the PXRD study, the IBU crystals were amorphized using the SH method. The elution rate of SH mixture containing 10 wt% IBU was approximately 2.7 times higher than that of the IBU crystals at 10 min after the start of the test. Based on these results, the SH method is a novel approach for amorphizing and enhancing the solubility of poorly water-soluble drugs without the use of organic solvents.

目前正在开发的许多活性药物成分（api）在水中是难溶的，这对其溶解度和生物利用度的提高提出了严峻的挑战。蒸发/冷凝（EV）方法，其中晶体原料药溶解在有机溶剂中并吸附在多孔材料上，用于提高原料药的溶解度。然而，在蒸发过程中使用残余有机溶剂是具有挑战性的。最近，密封加热（SH）方法，其中多孔材料和升华API的混合物在密封容器中加热，已被报道为EV方法的替代方法。本研究的重点是介孔二氧化硅（MPS-4R或-2R）作为多孔材料。采用SH法研究了布洛芬（ibuprofen， IBU）在mps上的吸附。在PXRD研究中，采用SH法对IBU晶体进行非晶化。在试验开始后10分钟，含10 wt% IBU的SHM的洗脱率比IBU晶体的洗脱率高约2.7倍。基于这些结果，SH方法是一种不使用有机溶剂而非非晶化和提高水溶性差药物溶解度的新方法。

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引用次数: 0

Dermal disposition characterization and development of a retrospective level A in vitro-in vivo relationship for topical metronidazole products. 外用甲硝唑产品的皮肤倾向特征和回顾性a级体内外关系的发展。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2025-12-24 DOI: 10.1016/j.xphs.2025.104139

Benjamin A Kuzma, Sharareh Senemar, Tannaz Ramezanli, Priyanka Ghosh, Sam G Raney, Grazia Stagni

Dermal microdialysis involves the insertion of a probe into the dermis beneath an application site for a topical drug product (TDP). The probe measures local, unbound, active pharmaceutical ingredient (API or drug) concentrations in the dermis. The resulting dermal concentration-time profile is a combination of the simultaneous drug absorption and disposition (by distribution/elimination into surrounding tissues and into the dermal vasculature). For orally or subcutaneously administered drug products, the absorption process is estimated through deconvolution of plasma concentrations utilizing the unit impulse response (UIR) obtained from an intravenous administration. In this study, we implemented a retrodialysis/microdialysis (termed "dermal infusion") approach to deliver metronidazole (MTZ) directly into the dermis allowing measurement of dermal disposition parameters (dermal clearance and dermal volume of distribution) and thus the calculation of MTZ's dermal UIR (dUIR); The dUIR allowed for the estimation of the absorption process or in vivo dermal flux (input-rate) and cumulative amount (CA) permeated from MTZ TDP application. The in vivo (Yucatan mini-pig) CA permeated were compared with in vitro permeation testing data (human) to build a retrospective in vitro - in vivo relationship (IVIVR). The internal validation for C_max and AUC_0-48hr prediction errors indicated a reliable IVIVR. These results suggest that the dermal infusion approach can be used to study dermal API disposition, which can aid in the comprehension of in vivo cutaneous pharmacokinetic (cPK) data. Furthermore, a mechanistic cPK understanding is essential for the successful development of new topical therapeutics and assessment of bioequivalence of TDPs, alike.

皮肤微透析涉及将探针插入局部药物产品（TDP）应用部位下方的真皮。探针测量真皮中局部，未结合的活性药物成分（API或药物）浓度。由此产生的皮肤浓度-时间曲线是同时药物吸收和处置（通过分布/消除进入周围组织和进入皮肤血管系统）的组合。对于口服或皮下给药的药物，吸收过程是通过利用从静脉给药获得的单位脉冲响应（UIR）对血浆浓度进行反卷积来估计的。在这项研究中，我们实施了一种反透析/微透析（称为“真皮输注”）方法，将甲硝唑（MTZ）直接输送到真皮中，从而测量真皮配置参数（真皮清除率和真皮分布体积），从而计算MTZ的真皮UIR (dUIR)；dUIR允许估计吸收过程或体内皮肤通量（输入率）和累积量（CA）从MTZ TDP应用渗透。将体内（尤卡坦迷你猪）CA的渗透与体外（人）CA的渗透测试数据进行比较，建立回顾性的体外-体内关系（IVIVR）。Cmax和auc0 -48小时预测误差的内部验证表明，IVIVR是可靠的。这些结果表明，皮肤输注方法可用于研究API的皮肤分布，这有助于理解体内皮肤药代动力学（cPK）数据。此外，了解cPK的机制对于成功开发新的局部疗法和评估tdp的生物等效性至关重要。

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引用次数: 0

Augmenting the cytotoxicity and apoptosis induction of green synthesized copper oxide nanoparticles from Artemisia sieberi by combining with tamoxifen: Mechanism involving Bax/Bcl-2 modulation 他莫昔芬联合青蒿绿色合成氧化铜纳米颗粒增强细胞毒性和诱导凋亡：Bax/Bcl-2调节机制

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2025-12-23 DOI: 10.1016/j.xphs.2025.104143

Saeed Seghatoleslami , Mohammadreza Pourmohammad , Homa Mahmoudzadeh , Jina Khayatzadeh

Treatment of breast cancer is severely hindered by dose-limiting toxicity and acquired Tamoxifen (Tam) resistance. This study investigated the synergistic anti-cancer effect and molecular mechanism of green-synthesized Copper Oxide Nanoparticles (CuO NPs) when combined with Tam against the MCF−7 human breast cancer cell line. CuO NPs were successfully produced using an aqueous extract of Artemisia sieberi as a dual reducing/capping agent. Characterization confirmed the formation of stable nanoparticles, evidenced by a Surface Plasmon Resonance (SPR) peak at 552 nm, an average size of ∼36 nm (TEM), and excellent colloidal stability with a highly negative Zeta Potential (-33.5 mV). The MTT assay demonstrated that the combination regimen exhibited a strong synergistic cytotoxic effect (CI<1) toward MCF−7 cells. Synergy was achieved even at low concentrations, such as 15.0 μg/mL CuO NPs:1.0 μM Tam (CI=0.99), with the most potent synergy (CI=0.69) observed at the maximum dose. Quantitative analysis via Annexin V/PI flow cytometry confirmed this enhancement, showing the combination reduced the viable cell population to a minimal 4.87 %. Mechanistically, RT−qPCR analysis revealed a maximal perturbation of the mitochondrial apoptotic pathway. The combined treatment simultaneously maximized the up-regulation of the pro-apoptotic gene BAX and the down-regulation of the anti-apoptotic gene BCL−2. This synergistic action resulted in a 16.74-fold increase in the critical BAX/BCL−2 ratio, approximately two times greater than either monotherapy. These findings validate CuO NPs co-administration with Tamoxifen as a promising strategy for overcoming acquired Tamoxifen resistance.

剂量限制性毒性和获得性他莫昔芬（Tam）耐药性严重阻碍了乳腺癌的治疗。本研究探讨了绿色合成的氧化铜纳米颗粒（CuO NPs）与Tam联合对MCF-7人乳腺癌细胞系的协同抗癌作用及其分子机制。采用青蒿水提物作为双还原/封盖剂，成功制备了CuO NPs。表征证实形成了稳定的纳米颗粒，表面等离子体共振（SPR）峰位于552 nm，平均尺寸为~ 36 nm (TEM)，具有优异的胶体稳定性，具有高度负的Zeta电位（-33.5 mV）。MTT试验表明，联合用药方案具有较强的协同细胞毒作用（CI）

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引用次数: 0

A pharmaceutical developability perspective on antibodies with ultra-long CDRs 超长cdr抗体的药物开发前景。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2025-12-23 DOI: 10.1016/j.xphs.2025.104142

Marcel Passon , Stefaan De Smedt , Hristo L. Svilenov

Antibodies with ultralong complementarity-determining regions (ulCDRs) have unique antigen-binding features with considerable potential for biomedical applications. Despite this potential, their stability and developability remain largely unexplored from a pharmaceutical perspective. Here, we present a systematic analysis of Fab fragments containing ulCDRs using assays for therapeutic antibody candidate selection. Fluorescence- and light-scattering-based analyses across a broad pH range revealed that ulCDR Fabs exhibit good thermal stability and minimal aggregation. Furthermore, we used relative solubility measurements and light scattering to evaluate the colloidal stability of the Fabs and identified the ulCDR as a key determinant of weak self-association. In addition, stress and storage studies demonstrated that ulCDR Fabs maintain high stability under mechanical stress and at elevated temperature. The results show that ulCDR Fabs display overall favorable physical stability. At the same time, colloidal properties governed by weak ulCDR-driven self-interactions represent the main factor likely to differentiate individual antibodies within this class.

具有超长互补决定区（ulcdr）的抗体具有独特的抗原结合特性，在生物医学应用中具有相当大的潜力。尽管有这种潜力，但从药学的角度来看，它们的稳定性和可发展性在很大程度上仍未得到探索。在这里，我们提出了包含ulCDRs的Fab片段的系统分析，使用检测方法进行治疗性候选抗体的选择。基于荧光和光散射的分析显示，在广泛的pH范围内，ulCDR晶圆片表现出良好的热稳定性和最小的聚集。此外，我们使用相对溶解度测量和光散射来评估fab的胶体稳定性，并确定ulCDR是弱自缔合的关键决定因素。此外，应力和存储研究表明，ulCDR晶圆片在机械应力和高温下保持高稳定性。结果表明，ulCDR晶圆片整体具有良好的物理稳定性。与此同时，由弱ulcdr驱动的自相互作用控制的胶体特性代表了这类抗体中可能区分个体抗体的主要因素。

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引用次数: 0