International Journal of Pharmaceutics最新文献_第8页

A contact lens-embedded betaine ester polymer for pH-responsive release of an osmoprotectant to the corneal surface 一种隐形眼镜内嵌甜菜碱酯聚合物，用于渗透保护剂在角膜表面的ph响应释放。

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2026-02-20 Epub Date: 2026-01-19 DOI: 10.1016/j.ijpharm.2026.126594

Dan Hawthorne , Cheng-Chun Peng , Emma Ward , Susan Sandeman , Ananth SV Pannala , Dharmendra Jani , Inna Maltseva , Andrew W Lloyd

Topical delivery of osmoprotectants to ocular surface has been shown to be a promising solution to ocular discomfort thought to be associated with corneal hyperosmolarity. Currently, most osmoprotectants are administrated by aqueous eyedrops, which are associated with poor bioavailability and short residence time in the tear film, requiring repeated dosing to maintain the osmoprotectant concentration above the effective level. In response to this challenge, this work describes poly(vinyl glycine betaine) (PV-GB), a degradable ester quat polymer which gradually releases the osmoprotectant, glycine betaine (GB), over a period of days to weeks, with release rate strongly dependent on pH of its surroundings. PV-GB was embedded into commercial contact lenses (CLs) alongside a polyanion, hyaluronic acid (HA), to provide extended release of GB during a period reflecting the typical usage of a daily disposable CL wear of 8 – 16 h. A GB release lifetime of ≪48 hrs was achieved from a system comprising PV-GB/HA embedded within an anionic CL using a simple soaking method. Further experiments indicated the polymer was stable to autoclave sterilisation, had a shelf-life of 6 + months (under optimised solution conditions), and was likely to be mucoadhesive, which would be expected to enhance bioavailability of GB at the ocular surface.

眼表局部递送渗透保护剂已被证明是一种有希望的解决与角膜高渗有关的眼部不适的方法。目前，大多数渗透保护剂是通过水滴眼液给药，这与生物利用度差和在泪膜中的停留时间短有关，需要反复给药以保持渗透保护剂浓度高于有效水平。为了应对这一挑战，本研究描述了聚乙烯基甜菜碱（PV-GB），一种可降解的酯类四元聚合物，在几天到几周的时间内逐渐释放渗透保护剂甜菜碱（GB），其释放速度强烈依赖于周围环境的pH值。将PV-GB与聚阴离子透明质酸（HA）一起嵌入商用隐形眼镜（CL）中，以提供GB在一段时间内的延长释放，反映每日一次性隐形眼镜佩戴8 - 16 h的典型使用情况。采用简单的浸泡方法，将PV-GB/HA嵌入阴离子CL中，使该系统的GB释放寿命≪48小时。进一步的实验表明，该聚合物在高压灭菌中是稳定的，保质期为6 + 个月（在优化的溶液条件下），并且可能具有黏附性，这有望提高GB在眼表的生物利用度。

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引用次数: 0

Synergistic photo/chemo-therapeutic liposome induced pyroptosis and anti-tumor immunity in head and neck squamous cell carcinoma 协同光/化学治疗脂质体诱导头颈部鳞状细胞癌的焦亡和抗肿瘤免疫。

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2026-02-20 Epub Date: 2026-01-09 DOI: 10.1016/j.ijpharm.2026.126565

Yahui Zhang , Liya Yu , Yehui Kang , Yuxiang Zhang , Jiaxin Li , Yu Cai , Jiajie Xu

Head and Neck Squamous Cell Carcinoma (HNSCC), characterized by a propensity for recurrence and metastasis, underscores the inadequacies of existing treatments. In this research, a liposome called DI@Lipo was developed to co-deliver cisplatin (DDP) and indocyanine green (ICG), aiming to trigger synergistic pyroptosis to enhance antitumor immunity. DI@Lipo cleverly harnessed the light-activated powers of ICG, combined them with DDP’s tumor-killing ability, to induce activation of the NLRP3 inflammasome. This, in turn, spurred gasdermin D into action, setting off a fiery pyroptosis. This chain reaction triggered a substantial release of Damage-Associated Molecular Patterns (DAMPs) and inflammatory cytokines, which in turn stimulated dendritic cells to mature and attracted an influx of killer T cells. In murine models of HNSCC, this combination therapy not only effectively eliminated primary tumors but also induced a potent abscopal effect, suppressing untreated distant tumors. Importantly, this treatment improved overall survival rates without causing notable systemic toxicity. Additionally, the DI@Lipo platform facilitated fluorescence and photoacoustic imaging (PAI) for potential treatment monitoring. These findings highlight how DI@Lipo-triggered pyroptosis could effectively transform immunologically dormant tumors into responsive ones, presenting a practical therapeutic avenue to combat treatment resistance in head and neck squamous cell carcinoma.

头颈部鳞状细胞癌（HNSCC）以复发和转移倾向为特征，强调了现有治疗方法的不足。本研究开发了一种名为DI@Lipo的脂质体，用于共递送顺铂（DDP）和吲哚菁绿（ICG），旨在触发协同焦亡，增强抗肿瘤免疫。DI@Lipo巧妙地利用ICG的光激活能力，将它们与DDP的肿瘤杀伤能力结合起来，诱导NLRP3炎性体的激活。这反过来又刺激了气皮素D的作用，引发了炽热的焦亡。这一连锁反应引发了损伤相关分子模式（DAMPs）和炎症细胞因子的大量释放，进而刺激树突状细胞成熟并吸引杀伤T细胞的涌入。在HNSCC小鼠模型中，这种联合治疗不仅有效地消除了原发肿瘤，而且还诱导了强大的体外作用，抑制了未治疗的远处肿瘤。重要的是，这种治疗提高了总生存率，而没有引起明显的全身毒性。此外，DI@Lipo平台促进了荧光和光声成像（PAI）用于潜在治疗监测。这些发现突出了DI@Lipo-triggered焦亡如何有效地将免疫休眠的肿瘤转化为应答性肿瘤，为头颈部鳞状细胞癌的治疗抵抗提供了一种实用的治疗途径。

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引用次数: 0

Multiscale simulation of stratum corneum lipid mixtures: effects of ceramide headgroups on structural organization and hydrogen bonding networks 角质层脂质混合物的多尺度模拟：神经酰胺头基团对结构组织和氢键网络的影响。

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2026-02-20 Epub Date: 2026-01-09 DOI: 10.1016/j.ijpharm.2026.126573

Chloe O. Frame , Christopher R. Iacovella , David J. Moore , Annette L. Bunge , Clare McCabe

The barrier function of the outermost layer of human skin, the stratum corneum (SC), arises from its multilamellar lipid matrix composed primarily of ceramides (CERs), cholesterol (CHOL), and free fatty acids (FFAs). Coarse-grained (CG) and atomistic molecular dynamics simulations have been used to study self-assembled multilayers comprising CERs NS, NP, AS, and AP, in pure CER systems and mixtures of CERs with CHOL and FFAs. Equilibrated CG configurations were reverse-mapped to recover atomistic details and analyzed to extract structures and hydrogen bonding. Simulations of pure CERs agreed with experimental trends: phytosphingosine CERs (NP and AP) exhibited more CO hydrogen bonds, consistent with lower amide I FTIR frequencies, than their sphingosine counterparts (NS and AS). Likewise, non-hydroxy CERs (NS and NP) exhibited more CO hydrogen bonding than their α-hydroxy analogs (AS and AP). CER mixtures with CHOL and FFA showed reduced CO hydrogen bonding compared to pure CERs, though this effect depended on water content. Hydroxyl location was critical: OH on the phytosphingosine base increased CO hydrogen bonding, whereas the α-hydroxy on the acyl chain reduced it. In CER NP:AP mixtures with CHOL and FFA, simulations reproduced the experimental repeat distances for NP-rich and AP-rich systems despite differences in hydrogen bonding. Simulations of multicomponent mixtures resembling the SC model of Bouwstra demonstrated the dominant effect of chain-length distribution, rather than CER hydrogen bonding, on permeability. This work shows how multiscale modeling integrated with experiments can uncover molecular mechanisms linking composition and SC barrier structure to interpret experimental results.

人体皮肤最外层角质层（SC）的屏障功能源于其多层脂质基质，主要由神经酰胺（CERs）、胆固醇（CHOL）和游离脂肪酸（FFAs）组成。粗粒度（CG）和原子分子动力学模拟被用于研究在纯CER体系和CER与CHOL和FFAs的混合物中，由CERs NS、NP、AS和AP组成的自组装多层膜。平衡的CG构型被反向映射以恢复原子细节，并分析提取结构和氢键。纯cer的模拟与实验趋势一致：植物鞘醇cer （NP和AP）比它们的鞘醇cer （NS和AS）表现出更多的CO氢键，与酰胺I FTIR频率较低一致。同样，非羟基cer （NS和NP）比α-羟基类似物（AS和AP）表现出更多的CO氢键。与纯CER相比，与CHOL和FFA混合的CER显示CO氢键减少，尽管这种影响取决于含水量。羟基的位置至关重要：植物鞘苷基上的羟基增加了CO的氢键，而酰基链上的α-羟基则减少了CO的氢键。在含有CHOL和FFA的CER NP:AP混合物中，模拟再现了富NP和富AP体系的实验重复距离，尽管氢键存在差异。对类似Bouwstra SC模型的多组分混合物的模拟表明，链长分布对渗透率的主要影响，而不是CER氢键。这项工作表明，多尺度建模与实验相结合，可以揭示分子机制连接组成和SC势垒结构，以解释实验结果。

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引用次数: 0

Multidisciplinary approaches for the prevention and management of capsular contracture: a review of clinical, pharmacological, and biomaterial-based strategies 预防和管理包膜挛缩的多学科方法：临床，药理学和生物材料为基础的策略综述。

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2026-02-20 Epub Date: 2026-01-22 DOI: 10.1016/j.ijpharm.2026.126602

Mohuya Paul , Woo Jin Song , Jungkyun Im

Capsular contracture (CC) is the most frequent complication associated with silicone-based breast implant surgery and often leads to multiple revision surgeries. The implantation of a foreign object triggers the formation of a fibrous capsule around the silicone implant. Over time, excessive and uncontrollable fibrosis leads to capsule thickening and contraction, resulting in severe pain, discomfort, and implant distortion, all hallmarks of CC. Various strategies have been proposed to prevent or mitigate CC. One common strategy is surface modification of the silicone implant by introducing texture. Implant surface coating with antifibrotic and anti-inflammatory drugs is another common strategy to regulate CC. Anti-inflammatory drugs such as leukotriene inhibitor antagonists (LTRAs) and NSAIDs have demonstrated preventive effects against CC. Recently, the omega-3 polyunsaturated fatty acids (ω3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have emerged as promising candidates due to their anti-inflammatory and anti-fibrotic properties. These naturally abundant compounds have shown potential to reduce collagen deposition, thin the fibrotic capsule, and downregulate fibrosis-related inflammatory cytokines. We also discuss the molecular mechanisms by which ω3 PUFAs exert their effects and compare their advantages over conventional treatments. Overall, this narrative review outlines the current understanding of CC pathophysiology and highlights existing preventive strategies from clinical, pharmacological and biomaterial-based approaches, providing a foundation for future research on the prevention of CC.

囊膜挛缩（CC）是与硅胶乳房植入手术相关的最常见的并发症，经常导致多次翻修手术。异物的植入触发硅酮植入物周围纤维囊的形成。随着时间的推移，过度和不可控的纤维化导致囊膜增厚和收缩，导致严重的疼痛、不适和植入物变形，这些都是CC的特征。人们提出了多种策略来预防或减轻CC，一种常见的策略是通过引入质地来修饰硅胶植入物的表面。抗炎药物如白三烯抑制剂拮抗剂（LTRAs）和非甾体抗炎药（NSAIDs）等抗炎药物已被证明对CC有预防作用，最近，ω -3多不饱和脂肪酸（ω3 PUFAs）、二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）因其抗炎和抗纤维化的特性而成为有希望的候选药物。这些天然丰富的化合物已显示出减少胶原沉积、使纤维化囊变薄和下调纤维化相关炎症细胞因子的潜力。我们还讨论了ω3 pufa发挥作用的分子机制，并比较了ω3 pufa相对于传统治疗的优势。总的来说，本文概述了目前对CC病理生理的理解，并强调了从临床、药理学和基于生物材料的方法中现有的预防策略，为未来的CC预防研究提供了基础。

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引用次数: 0

Preparation of high-performance PVA@Fe3O4 magnetothermal microspheres for precise ablation of orthotopic hepatocellular carcinoma in a rabbit model 制备高性能PVA@Fe3O4磁热微球用于兔原位肝癌模型的精确消融。

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2026-02-20 Epub Date: 2026-01-17 DOI: 10.1016/j.ijpharm.2026.126590

Hao Zhang , Shenzhi Li , Jiaxi You , Liang Yin , Di Wang , Weiwei Zheng , Qiang Yuan , Yong Jin , Xingwei Sun

Globally, hepatocellular carcinoma (HCC) is among the most prevalent malignancies and is the third most common cause of cancer-related mortality. Thermal ablation therapies for hepatocellular carcinoma, such as microwave ablation (MWA) and radiofrequency ablation (RFA) guided by imaging devices, have been widely used in clinical practice and have achieved good therapeutic efficacy but still face the difficult problems of high dependence on the experience of the operator’s puncture and damage caused by the tissue puncture. In this study, magnetothermal microspheres (MMs) loaded with Fe₃O₄ nanoparticles, featuring a uniform particle size (45–55 μm) and a good eddy current heating effect, were prepared from polyvinyl alcohol (PVA) via Shirasu Porous Glass (SPG) membrane emulsification. Under the action of a high-frequency alternating magnetic field (AMF), the PVA@Fe₃O₄ MMs could be rapidly warmed in vitro and effectively inhibited the activity of tumor cells. We successfully constructed a rabbit VX2 orthotopic liver tumor model. Under DSA guidance, the microspheres were enriched precisely in the tumor tissue, and in vivo animal experiments confirmed that the therapeutic effect of the MMs was similar to that of puncture ablation under the effect of an AMF, and further sections of important organ tissues showed good in vivo safety. Compared with traditional percutaneous ablation, microsphere-mediated magnetic thermal ablation (MTA) significantly reduces puncture trauma and is applicable to other blood-rich solid tumors, demonstrating favorable clinical prospects.

在全球范围内，肝细胞癌（HCC）是最常见的恶性肿瘤之一，也是癌症相关死亡的第三大常见原因。肝细胞癌的热消融治疗，如成像装置引导下的微波消融（MWA）、射频消融（RFA）等，已广泛应用于临床，取得了良好的治疗效果，但仍面临着对操作者穿刺经验依赖程度高、穿刺组织损伤等难题。以聚乙烯醇（PVA）为原料，采用Shirasu多孔玻璃（SPG）膜乳化法制备了粒径均匀（45-55 μm）、涡流加热效果好的Fe3O4纳米颗粒磁热微球（mm）。在高频交变磁场（AMF）作用下，PVA@Fe3O4 mm在体外快速升温，有效抑制肿瘤细胞活性。我们成功构建了兔VX2原位肝肿瘤模型。在DSA引导下，微球在肿瘤组织中被精确富集，体内动物实验证实mmms的治疗效果与AMF作用下的穿刺消融相似，对重要器官组织的进一步切片显示出良好的体内安全性。与传统经皮消融相比，微球介导磁热消融（MTA）可显著减少穿刺创伤，并适用于其他富血实体肿瘤，具有良好的临床应用前景。

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引用次数: 0

Process optimization in pharmaceutical hot-melt extrusion: real-time volatile detection via SIFT-MS combined with multivariate analysis 医药热熔挤压工艺优化：SIFT-MS结合多变量分析实时挥发性检测。

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2026-02-20 Epub Date: 2026-01-25 DOI: 10.1016/j.ijpharm.2026.126623

Aaron D. Smith , Ecaterina Bordos , Michael Devlin , Colin Hastie , Mark J. Perkins , Vaughan S. Langford , Alastair J. Florence , John Robertson

Establishing robust processing windows for pharmaceutical polymers during hot-melt extrusion (HME) remains challenging, as conventional thermal analyses reveal little about early chemical change. Here, selected-ion-flow-tube-mass-spectrometry (SIFT-MS) combined with principal component analysis (PCA) was used to characterise real-time volatile evolution under both thermogravimetric (TGA) and extrusion conditions. Centroid-distance mapping and PCA loadings revealed distinct transitions, providing a data-driven means of defining the onset of significant chemical change. Across four representative polymers (Soluplus®, Affinisol™15LV, Kollidon® VA64, and Plasdone™ S630 Ultra), each exhibited changes in volatile composition that marked the onset of temperature-driven chemical evolution. Soluplus® and Plasdone™ S630 Ultra remained stable up to ≈190 °C with optimum extrusion ranges of 150–170 °C. Kollidon® VA64 showed earlier volatile emergence near 180 °C, defining a 160–180 °C window, while Affinisol™15LV, the most viscous system, degraded above 190–200 °C, narrowing its range to 170–185 °C. A brief rheological assessment supported these chemically defined limits, confirming that changes in volatile composition coincide with softening behaviour. Overall, SIFT-MS detected subtle, low-level volatile changes that emerge well before conventional thermal indicators, enabling rapid, non-destructive definition of polymer-specific extrusion windows and enhancing process understanding in amorphous solid dispersion manufacture. Through this analysis we were able to provide a narrower processing range than those defined by their respective manufacturers.

在热熔挤压（HME）过程中，为药用聚合物建立稳健的加工窗口仍然具有挑战性，因为传统的热分析几乎无法揭示早期化学变化。在这里，选择离子流管质谱（SIFT-MS）结合主成分分析（PCA）来表征热重（TGA）和挤压条件下的实时挥发性演变。质心距离映射和PCA加载揭示了明显的转变，提供了一种数据驱动的方法来定义重大化学变化的开始。在四种具有代表性的聚合物（Soluplus®，Affinisol™15LV， Kollidon®VA64和Plasdone™S630 Ultra）中，每种聚合物都表现出挥发性成分的变化，标志着温度驱动化学演化的开始。Soluplus®和Plasdone™S630 Ultra保持稳定高达≈190 °C，最佳挤出范围为150-170 °C。Kollidon®VA64在180 °C附近显示出较早的挥发性出现，定义了160-180 °C的窗口，而Affinisol™15LV是最粘稠的系统，在190-200 °C以上降解，将其范围缩小到170-185 °C。一项简短的流变学评估支持了这些化学定义的极限，证实了挥发性成分的变化与软化行为一致。总体而言，SIFT-MS检测到微妙的、低水平的挥发性变化，这些变化在传统的热指标之前就出现了，从而能够快速、无损地定义聚合物特定的挤出窗口，并增强了对非晶固体分散体制造过程的理解。通过这种分析，我们能够提供比各自制造商定义的加工范围更窄的加工范围。

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引用次数: 0

Aerosol delivery of salbutamol and terbutaline via a CE-marked medical vaping device: aerosol characterization and transfer efficiency compared to nebulization 沙丁胺醇和特布他林通过ce标记的医疗电子烟装置的气溶胶输送：与雾化相比，气溶胶特性和传递效率。

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2026-02-20 Epub Date: 2026-01-22 DOI: 10.1016/j.ijpharm.2026.126601

Faustine Fournel , Clément Mercier , Sophie Hodin , Jérémie Pourchez

Pulmonary delivery of bronchodilators remains challenging due to dose variability and suboptimal deposition with conventional inhalers and nebulizers. Thermal aerosolization via vaping devices has emerged as a promising alternative for controlled and reproducible delivery of active pharmaceutical ingredients (APIs). This study evaluates a CE-marked medical-grade vaping device (BIKY Breathe) for pulmonary delivery of salbutamol sulfate and terbutaline sulfate, assessing aerosol performance, particle size, and transfer efficiency, with comparison to a standard pneumatic nebulizer (Cirrus™2). Aerosols were generated under standardized puffing conditions and analyzed using a Glass Twin Impinger (GTI) and a Next Generation Impactor (NGI). Four API concentrations were tested to determine respirable dose, mass median aerodynamic diameter (MMAD), and emitted-dose reproducibility. The Cirrus™2 nebulizer served as reference. The tested device produced aerosols with MMADs of 1.10 ± 0.10 µm (terbutaline) and 1.13 ± 0.14 µm (salbutamol) indicating suitability for deep-lung deposition. Average aerosol mass per puff was ∼ 6 mg for both APIs with low inter-puff variability. Terbutaline achieved a maximum transfer efficiency of ∼ 40% at 1.35–1.80 mg/mL, whereas salbutamol did not exceed 10%, likely due to physicochemical constraints. Compared with the Cirrus™2 nebulizer, the vaping device generated more efficient micron aerosols and provided higher reproducibility of respirable doses. Overall, the CE-marked device demonstrates robust and reproducible aerosolization of bronchodilators, with particle size appropriate for deep-lung delivery. Terbutaline shows strong translational potential, while salbutamol would benefit from further formulation optimization. These in vitro results support the use of medical-grade vaping devices as promising platforms for pulmonary delivery of conventional and novel APIs.

由于传统吸入器和雾化器的剂量变异性和次优沉积，支气管扩张剂的肺输送仍然具有挑战性。通过电子烟装置进行热雾化已成为活性药物成分（api）受控和可重复输送的一种有前途的替代方法。本研究评估了ce标志的医疗级雾化装置（BIKY Breathe）用于肺输送硫酸沙丁胺醇和硫酸特布他林，评估了气溶胶性能、粒径和传输效率，并与标准气动雾化器（Cirrus™2）进行了比较。在标准化雾化条件下产生气溶胶，并使用玻璃双冲击器（GTI）和下一代冲击器（NGI）进行分析。检测了4种API浓度，以确定呼吸剂量、空气动力学质量中值直径（MMAD）和释放剂量的可重复性。Cirrus™2喷雾器作为参考。所测试的设备产生的气溶胶的MMADs为1.10 ± 0.10 µm（特布他林）和1.13 ± 0.14 µm（沙丁胺醇），表明适合深肺沉积。两种原料药的每次雾化的平均气溶胶质量为 ~ 6mg，雾化间可变性较低。特布他林在1.35-1.80 mg/mL时的最大传递效率为 ~ 40%，而沙丁胺醇不超过10%，可能是由于物理化学的限制。与Cirrus™2雾化器相比，该雾化装置产生更有效的微米气溶胶，并提供更高的可吸入剂量的再现性。总体而言，ce标记的设备显示出支气管扩张剂雾化的鲁棒性和可重复性，颗粒大小适合深肺输送。特布他林具有较强的转化潜力，而沙丁胺醇还需进一步优化配方。这些体外实验结果支持使用医疗级电子烟设备作为肺输送传统和新型原料药的有前途的平台。

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引用次数: 0

A novel epidermal mimicking phospholipid vesicle-based permeation assay: EpiPVPA for in vitro permeation evaluation 一种新型的表皮模拟磷脂囊泡渗透试验：EpiPVPA体外渗透评价。

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2026-02-20 Epub Date: 2026-01-18 DOI: 10.1016/j.ijpharm.2026.126595

Yuzhe Wang , Lu Sheng , Lin Bu , Huijuan Li , Jianxin Wu , Qing Huang

Phospholipid vesicle-based permeation assay (PVPA) is widely applied as in vitro skin alternative model by mimicking stratum corneum to evaluate the transdermal application of drugs and chemicals. However, it is composed of lipid components only, which suffer from limitations of achieving accurate permeability prediction. To remedy this shortcoming, inactive immortalized human keratinocytes (HaCaT) were integrated as component to construct epidermal-mimicking model: EpiPVPA. The EpiPVPA could tolerate the pH 3–10 as well as up to 30% ethanol and was stable for 2 weeks at 4 ℃. And the permeation evaluation by Franz diffusion test of 14 drugs demonstrated that EpiPVPA model is comparable to porcine skin with strong correlation. After quantitative structure–property relationship (QSPR) analysis of physicochemical descriptors of 14 drugs, HLB, TPSA, and log P were selected as main factors applied to build multiple linear regression (MLR) equation, and the corresponding linear correlation R² was elevated to 0.9010. EpiPVPA model is feasible to be applied to permeation evaluation of drugs and cosmetics.

磷脂囊泡渗透实验（PVPA）是一种模拟角质层的体外皮肤替代模型，被广泛应用于评价药物和化学物质的透皮作用。然而，它仅由脂质组分组成，在实现准确的渗透率预测方面存在局限性。为了弥补这一缺陷，我们将失活的永生化人角质形成细胞（HaCaT）整合为成分构建了表皮模拟模型：EpiPVPA。EpiPVPA可以耐受pH 3-10和高达30%的乙醇，在4 ℃下稳定2 周。通过Franz扩散试验对14种药物的渗透性评价表明，EpiPVPA模型与猪皮具有较强的相关性。对14种药物的理化描述符进行定量构效关系（QSPR）分析后，选择HLB、TPSA和log P作为主要因素建立多元线性回归（MLR）方程，其线性相关R2提升至0.9010。EpiPVPA模型可用于药品和化妆品的渗透评价。

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引用次数: 0

Prone-to-aggregate nanoparticle for cancer-targeted drug delivery 用于癌症靶向药物递送的一对一聚集体纳米颗粒。

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2026-02-20 Epub Date: 2026-01-20 DOI: 10.1016/j.ijpharm.2026.126600

Manisha Choudhary , Dnyaneshwar Kalyane , Devendra Choudhary , Nupur Vasdev , Muktika Tekade , Pinaki Sengupta , Rakesh Kumar Tekade

Nanoparticles (NPs) are emerging candidates in cancer management. Currently, they are extensively employed in biomedical applications, including drug delivery, imaging, sensing, gene therapy, photothermal therapy, photodynamic therapy, radiation therapy, immunotherapy, and magnetic hyperthermia, among others, for cancer management. Aggregating prone-to-aggregate NPs at the targeted site will help reduce off-target side effects and improve the efficacy of NPs. This diversity in NP applications is due to their dynamic surface properties, which allow their desired modifications for the intended application. Present NP research focuses on improving the efficacy of NPs by concentrating their distribution at the tumor site. This review discusses the prone-to-aggregate NPs aggregation approach to attain selective delivery at the tumor site following various stimuli (pH, enzyme, redox environment, temperature, interstitial fluid, magnetic field, light, etc.). Furthermore, this review also discusses the therapeutic and diagnostic applications of the prone-to-aggregate NPs aggregation approach in cancer therapy.

纳米颗粒（NPs）是癌症治疗的新兴候选者。目前，它们广泛应用于生物医学应用，包括药物输送、成像、传感、基因治疗、光热治疗、光动力治疗、放射治疗、免疫治疗、磁热疗等，用于癌症治疗。在靶向部位聚集proto -aggregate NPs有助于减少脱靶副作用，提高NPs的疗效。NP应用中的这种多样性是由于它们的动态表面特性，这允许它们对预期应用进行所需的修改。目前NP研究的重点是通过集中NP在肿瘤部位的分布来提高其疗效。这篇综述讨论了在各种刺激（pH、酶、氧化还原环境、温度、间质液、磁场、光等）下，原聚集体NPs聚集方法在肿瘤部位实现选择性递送。此外，本文还讨论了原-聚集NPs聚集方法在癌症治疗中的治疗和诊断应用。

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引用次数: 0

Stimuli-responsive smart nanocarriers for skin drug delivery 用于皮肤给药的刺激反应型智能纳米载体。

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2026-02-20 Epub Date: 2025-12-25 DOI: 10.1016/j.ijpharm.2025.126534

Ayyah Abdoh , Mohammad Imran , Khadeejeh Al-Smadi , Harsimran Kaur , Masood Ali , Tushar Kumeria , Yousuf Mohammed

Nanomaterials have improved skin drug delivery by facilitating the creation of smart, stimuli-responsive nanocarriers with increased therapeutic effectiveness. Internal or external stimuli can activate these systems, enabling controlled drug release. Internal stimuli-responsive nanocarriers use pathological alterations in diseased skin, like variations in pH, oxidative stress, enzymatic activity, or glucose concentrations, to trigger drug release exactly at the target sites. Conversely, external stimuli-responsive systems depend on physical stimuli such as temperature, light, electric fields, ultrasound, or magnetic fields, facilitating controlled release at specific times and sites. Collectively, these methods increase localized therapeutic precision, reduce systemic adverse effects, and improve therapeutic outcomes in dermatology. This review explores stimuli-responsive nanocarriers, focusing specifically on their use in skin drug delivery, highlighting their therapeutic advantages and limitations, and summarizing several studies using single- and dual-stimuli responsive systems for skin delivery in the treatment of dermatological disorders. The review also provides a critical overview of the analytical methods used to evaluate these nanocarriers, including in vitro, ex vivo, and in vivo models; physiochemical characterization; and advanced microscopic imaging, it also outlines their advantages and limitations. Finally, the paper concludes by delineating the present status of the field and identifying key challenges for future research to enhance the therapeutic use of stimuli-responsive nanocarriers for skin drug delivery.

纳米材料通过促进智能、刺激反应的纳米载体的产生，提高了治疗效果，从而改善了皮肤药物输送。内部或外部刺激可以激活这些系统，使药物释放可控。内部刺激反应纳米载体利用病变皮肤的病理改变，如pH值、氧化应激、酶活性或葡萄糖浓度的变化，在目标部位触发药物释放。相反，外部刺激响应系统依赖于物理刺激，如温度、光、电场、超声波或磁场，促进在特定时间和地点的控制释放。总的来说，这些方法提高了局部治疗的准确性，减少了全身不良反应，改善了皮肤病学的治疗结果。这篇综述探讨了刺激反应纳米载体，特别关注它们在皮肤给药中的应用，强调了它们的治疗优势和局限性，并总结了一些使用单和双刺激反应系统进行皮肤给药治疗皮肤病的研究。该综述还提供了用于评估这些纳米载体的分析方法的关键概述，包括体外，离体和体内模型；生化的特性;以及先进的显微成像，也概述了它们的优点和局限性。最后，本文总结了该领域的现状，并确定了未来研究的关键挑战，以加强刺激反应性纳米载体在皮肤药物输送中的治疗应用。

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引用次数: 0