International Journal of Pharmaceutics: X最新文献

pH/NIR dual-responsive implantable patch for combined photothermal and chemotherapy of tumors. pH/NIR双响应植入式贴片用于肿瘤光热化疗联合治疗。

IF 7.9 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2026-06-06 eCollection Date: 2026-06-01 DOI: 10.1016/j.ijpx.2026.100582

Wenjie Sun, Xi Zhang, Yili Zhao, Bixiang Ye, Wen Gao, Guangyi Jiang, Xin Li, Xiaoji Lin

The treatment of malignant solid tumors still faces challenges including the high risk of surgical resection and the severe side effects of chemotherapy. Moreover, existing clinical strategies often fail to meet the treatment needs of patients with inoperable tumors. In this study, a safe and efficient nanofiber patch was designed via electrospinning for combined photothermal-chemotherapy of abdominal tumors. By loading copper sulfide nanoparticles and polydopamine, the patch achieved efficient photothermal effects under safe NIR II laser irradiation. Moreover, the patch exhibited pH/NIR dual-responsive drug release through polydopamine protonation and photothermally enhanced diffusion. With these superior properties, the implantable patch can non-invasively ablate solid tumors via photothermal therapy and eliminate residual cancer cells through controllable chemotherapy, while maintaining low systemic toxicity. Notably, this safe and effective therapeutic strategy exhibited significantly higher tumor apoptosis (68.6%) than the control of only chemotherapy patch (29.3%) or photothermal therapy patch (42.5%). The DPPCP patch + NIR group exhibited dramatically decreased signal intensity, demonstrating superior antitumor efficacy. Moreover, the DPPCP patch enabled 100% survival of nude mice over 90 days. In this work, the patch-mediated combined photothermal-chemotherapy strategy holds promise as an alternative to clinical surgical resection and postoperative chemotherapy, addressing the treatment needs of diverse cancer patients.

恶性实体瘤的治疗仍面临手术切除风险高、化疗副作用严重等挑战。此外，现有的临床策略往往不能满足不能手术肿瘤患者的治疗需求。本研究采用静电纺丝法设计了一种安全高效的纳米纤维贴片，用于腹腔肿瘤的光热联合化疗。通过负载硫化铜纳米粒子和聚多巴胺，贴片在安全的近红外II型激光照射下获得了高效的光热效应。此外，该贴片通过多多巴胺质子化和光热增强扩散表现出pH/NIR双响应性药物释放。具有这些优越的性能，可植入贴片可以通过光热治疗无创消融实体瘤，通过可控化疗消除残留癌细胞，同时保持较低的全身毒性。值得注意的是，这种安全有效的治疗策略显示肿瘤凋亡（68.6%）明显高于仅化疗贴片（29.3%）或光热贴片（42.5%）的对照组。DPPCP贴片+ NIR组信号强度显著降低，显示出较好的抗肿瘤效果。此外，DPPCP贴片使裸鼠90天以上的存活率达到100%。在这项工作中，贴片介导的光热联合化疗策略有望成为临床手术切除和术后化疗的替代方案，满足不同癌症患者的治疗需求。

{"title":"pH/NIR dual-responsive implantable patch for combined photothermal and chemotherapy of tumors.","authors":"Wenjie Sun, Xi Zhang, Yili Zhao, Bixiang Ye, Wen Gao, Guangyi Jiang, Xin Li, Xiaoji Lin","doi":"10.1016/j.ijpx.2026.100582","DOIUrl":"10.1016/j.ijpx.2026.100582","url":null,"abstract":"<p><p>The treatment of malignant solid tumors still faces challenges including the high risk of surgical resection and the severe side effects of chemotherapy. Moreover, existing clinical strategies often fail to meet the treatment needs of patients with inoperable tumors. In this study, a safe and efficient nanofiber patch was designed via electrospinning for combined photothermal-chemotherapy of abdominal tumors. By loading copper sulfide nanoparticles and polydopamine, the patch achieved efficient photothermal effects under safe NIR II laser irradiation. Moreover, the patch exhibited pH/NIR dual-responsive drug release through polydopamine protonation and photothermally enhanced diffusion. With these superior properties, the implantable patch can non-invasively ablate solid tumors via photothermal therapy and eliminate residual cancer cells through controllable chemotherapy, while maintaining low systemic toxicity. Notably, this safe and effective therapeutic strategy exhibited significantly higher tumor apoptosis (68.6%) than the control of only chemotherapy patch (29.3%) or photothermal therapy patch (42.5%). The DPPCP patch + NIR group exhibited dramatically decreased signal intensity, demonstrating superior antitumor efficacy. Moreover, the DPPCP patch enabled 100% survival of nude mice over 90 days. In this work, the patch-mediated combined photothermal-chemotherapy strategy holds promise as an alternative to clinical surgical resection and postoperative chemotherapy, addressing the treatment needs of diverse cancer patients.</p>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"100582"},"PeriodicalIF":7.9,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13262176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ROS-responsive tegafur-pheophorbide a conjugate-loaded microneedles for deep drug delivery and chemo-photodynamic therapy of superficial tumors. 一种用于深部药物传递和浅表肿瘤化学光动力治疗的偶联负载微针。

IF 7.9 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2026-06-02 eCollection Date: 2026-06-01 DOI: 10.1016/j.ijpx.2026.100580

Anning Li, Yingjie Ma, Yunfeng Dai, Yibin Guo, Yanjun He, Sihan Chen, Xinjie Su, Chenxi Fang, Long Chen, Meitao Duan, Ming Chen, Jungang Ren, Li Wang, Chen Wang, Zhiqiang Zhang

Superficial tumors, including breast cancer, melanoma, and oral carcinoma, pose significant treatment challenges due to their anatomical location and the inherent limitations of conventional therapies, such as systemic toxicity and poor tumor specificity. Chemotherapy often leads to severe side effects, while photodynamic therapy (PDT) is hindered by the limited tissue penetration of both light and photosensitizers. To address these issues, we developed an innovative reactive oxygen species (ROS)-responsive drug delivery system based on a conjugate of tegafur (TF) and pheophorbide a (PPa) linked via a thioether bond. This prodrug (TF-TA-PPa) integrates chemotherapy and PDT into a single molecular entity, enabling synergistic anti-tumor effects. To enhance localized delivery and patient compliance, the conjugate was encapsulated into polymeric micelles and further incorporated into soluble microneedles (MNs) containing cell-penetrating peptides. The resulting TF-TA-PPa@PMN system enables painless transdermal administration, deep tumor penetration, and on-demand drug release triggered by near-infrared laser irradiation through ROS-mediated cleavage of the thioether linker. Comprehensive in vitro and in vivo evaluations demonstrated excellent biocompatibility, sustained drug release profiles, enhanced cellular uptake, and potent tumor suppression in a 4 T1 breast cancer model, achieving a remarkable tumor inhibition rate of 89.2% with minimal systemic toxicity. This integrated platform represents a promising strategy for the localized, combinatory treatment of superficial tumors with improved efficacy and reduced side effects.

浅表肿瘤，包括乳腺癌、黑色素瘤和口腔癌，由于其解剖位置和传统治疗的固有局限性，如全身毒性和肿瘤特异性差，给治疗带来了重大挑战。化疗常常导致严重的副作用，而光动力疗法（PDT）受到光和光敏剂有限的组织渗透的阻碍。为了解决这些问题，我们开发了一种创新的活性氧（ROS）反应药物递送系统，该系统基于硫醚键连接的替加氟（TF）和硫代酚a （PPa）的共轭物。这种前药（TF-TA-PPa）将化疗和PDT整合到一个单一的分子实体中，从而实现协同抗肿瘤作用。为了增强局部递送和患者依从性，缀合物被包裹在聚合物胶束中，并进一步掺入含有细胞穿透肽的可溶性微针（MNs）中。由此产生的TF-TA-PPa@PMN系统可以实现无痛的经皮给药，深层肿瘤穿透，以及由近红外激光照射通过ros介导的硫醚连接物裂解触发的按需药物释放。综合体外和体内评价表明，在4 T1乳腺癌模型中，该药物具有良好的生物相容性、持续的药物释放特征、增强的细胞摄取和有效的肿瘤抑制作用，肿瘤抑制率达到89.2%，全身毒性最小。该综合平台为浅表肿瘤的局部联合治疗提供了一种有前景的策略，提高了疗效，减少了副作用。

{"title":"ROS-responsive tegafur-pheophorbide a conjugate-loaded microneedles for deep drug delivery and chemo-photodynamic therapy of superficial tumors.","authors":"Anning Li, Yingjie Ma, Yunfeng Dai, Yibin Guo, Yanjun He, Sihan Chen, Xinjie Su, Chenxi Fang, Long Chen, Meitao Duan, Ming Chen, Jungang Ren, Li Wang, Chen Wang, Zhiqiang Zhang","doi":"10.1016/j.ijpx.2026.100580","DOIUrl":"10.1016/j.ijpx.2026.100580","url":null,"abstract":"<p><p>Superficial tumors, including breast cancer, melanoma, and oral carcinoma, pose significant treatment challenges due to their anatomical location and the inherent limitations of conventional therapies, such as systemic toxicity and poor tumor specificity. Chemotherapy often leads to severe side effects, while photodynamic therapy (PDT) is hindered by the limited tissue penetration of both light and photosensitizers. To address these issues, we developed an innovative reactive oxygen species (ROS)-responsive drug delivery system based on a conjugate of tegafur (TF) and pheophorbide a (PPa) linked <i>via</i> a thioether bond. This prodrug (TF-TA-PPa) integrates chemotherapy and PDT into a single molecular entity, enabling synergistic anti-tumor effects. To enhance localized delivery and patient compliance, the conjugate was encapsulated into polymeric micelles and further incorporated into soluble microneedles (MNs) containing cell-penetrating peptides. The resulting TF-TA-PPa@PMN system enables painless transdermal administration, deep tumor penetration, and on-demand drug release triggered by near-infrared laser irradiation through ROS-mediated cleavage of the thioether linker. Comprehensive <i>in vitro</i> and <i>in vivo</i> evaluations demonstrated excellent biocompatibility, sustained drug release profiles, enhanced cellular uptake, and potent tumor suppression in a 4 T1 breast cancer model, achieving a remarkable tumor inhibition rate of 89.2% with minimal systemic toxicity. This integrated platform represents a promising strategy for the localized, combinatory treatment of superficial tumors with improved efficacy and reduced side effects.</p>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"100580"},"PeriodicalIF":7.9,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13264333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ligand-modified liposomes as drug delivery systems for the active targeting of pancreatic cancer 配体修饰脂质体作为主动靶向胰腺癌的药物递送系统

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2026-06-01 Epub Date: 2026-01-02 DOI: 10.1016/j.ijpx.2026.100483

Yerin Jang , Jaehee Jang , Jaewoo Son , Hee-Young Lee , Jonghoon Choi

Pancreatic cancer is among the most fatal malignancies worldwide. The aggressive nature of this disease, coupled with late-stage diagnosis and limited therapeutic options, highlights the urgent need for innovative treatment approaches. Targeted therapy has emerged as a promising strategy to enhance therapeutic efficacy while minimizing systemic toxicity. Liposomes, as versatile nanoparticles, have shown significant potential to contribute to the develpment of drug delivery system. These lipid-based vesicles encapsulate chemotherapeutic drugs, shield them from degradation, and promote greater accumulation within tumor cites. Furthermore, liposomes can be surface-modifed with various ligands to improve their specificity and cellular uptake. Research on liposome-based targeted chemotherapy for pancreatic cancer has explored useful ligand-based strategies to enhance drug delivery to pancreatic cancer cells. In this review, liposome-based targeted strategies for pancreatic cancer are classified by ligand type, including antibodies, aptamers, carbohydrates, proteins and peptides, and integrates case studies to demonstrate how different targeting approaches translate into improved cellular uptake, therapeutic efficacy, and antitumor effects. In addition, emerging formulations such as dual-targeting liposomes are described, highlighting their potential to further strengthen treatment performance. The review summarizes the current research landscape of liposome-based targeted drug delivery systems for pancreatic cancer, providing insights into promising biomarkers and ligand-mediated targeting strategies. It further discusses broader opportunities for target exploration and liposomal design optimization, as well as future research directions aimed at overcoming existing limitations and improving therapeutic outcomes.

胰腺癌是世界上最致命的恶性肿瘤之一。这种疾病的侵袭性，加上晚期诊断和有限的治疗选择，突出了迫切需要创新的治疗方法。靶向治疗已成为一种有前途的策略，以提高治疗效果，同时尽量减少全身毒性。脂质体作为一种多用途的纳米颗粒，在药物传递系统的发展中显示出巨大的潜力。这些以脂质为基础的囊泡包裹化疗药物，保护它们免受降解，并促进肿瘤细胞内更大的积累。此外，脂质体可以用各种配体进行表面修饰，以提高其特异性和细胞摄取。基于脂质体的胰腺癌靶向化疗研究探索了有效的基于配体的策略来增强药物对胰腺癌细胞的递送。在这篇综述中，基于脂质体的胰腺癌靶向策略按配体类型分类，包括抗体、适体、碳水化合物、蛋白质和肽，并整合案例研究来证明不同的靶向方法如何转化为改善细胞摄取、治疗效果和抗肿瘤效果。此外，介绍了双靶向脂质体等新兴制剂，强调了它们进一步加强治疗性能的潜力。本文总结了目前基于脂质体的胰腺癌靶向药物递送系统的研究现状，为有前途的生物标志物和配体介导的靶向策略提供了见解。它进一步讨论了靶点探索和脂质体设计优化的更广泛机会，以及旨在克服现有局限性和改善治疗效果的未来研究方向。

{"title":"Ligand-modified liposomes as drug delivery systems for the active targeting of pancreatic cancer","authors":"Yerin Jang , Jaehee Jang , Jaewoo Son , Hee-Young Lee , Jonghoon Choi","doi":"10.1016/j.ijpx.2026.100483","DOIUrl":"10.1016/j.ijpx.2026.100483","url":null,"abstract":"<div><div>Pancreatic cancer is among the most fatal malignancies worldwide. The aggressive nature of this disease, coupled with late-stage diagnosis and limited therapeutic options, highlights the urgent need for innovative treatment approaches. Targeted therapy has emerged as a promising strategy to enhance therapeutic efficacy while minimizing systemic toxicity. Liposomes, as versatile nanoparticles, have shown significant potential to contribute to the develpment of drug delivery system. These lipid-based vesicles encapsulate chemotherapeutic drugs, shield them from degradation, and promote greater accumulation within tumor cites. Furthermore, liposomes can be surface-modifed with various ligands to improve their specificity and cellular uptake. Research on liposome-based targeted chemotherapy for pancreatic cancer has explored useful ligand-based strategies to enhance drug delivery to pancreatic cancer cells. In this review, liposome-based targeted strategies for pancreatic cancer are classified by ligand type, including antibodies, aptamers, carbohydrates, proteins and peptides, and integrates case studies to demonstrate how different targeting approaches translate into improved cellular uptake, therapeutic efficacy, and antitumor effects. In addition, emerging formulations such as dual-targeting liposomes are described, highlighting their potential to further strengthen treatment performance. The review summarizes the current research landscape of liposome-based targeted drug delivery systems for pancreatic cancer, providing insights into promising biomarkers and ligand-mediated targeting strategies. It further discusses broader opportunities for target exploration and liposomal design optimization, as well as future research directions aimed at overcoming existing limitations and improving therapeutic outcomes.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100483"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921844","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

Enhancing islet transplantation outcomes in T1DM: The promise of mesenchymal stem cells and exosomes 增强胰岛移植治疗T1DM的结果：间充质干细胞和外泌体的前景

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2026-06-01 Epub Date: 2026-01-31 DOI: 10.1016/j.ijpx.2026.100498

Ying Zhang , Xiaoyue Chen , Zhuoxun Huang , Yifan Qiu , Longfa Kou , Qing Yao

Islet transplantation represents a promising therapeutic strategy for type 1 diabetes mellitus (T1DM), yet its clinical application is constrained by hypoxia, oxidative stress, and immune rejection during islet isolation, culture, and post-transplantation. In recent years, mesenchymal stem cells (MSCs) have demonstrated the ability to enhance islet survival and function through immunomodulation, anti-inflammatory effects, and paracrine signaling. Among the secreted components, exosomes have emerged as key mediators of MSC function, capable of delivering nucleic acids, proteins, and lipids to target cells with high biocompatibility and low immunogenicity. This review highlights recent advances in utilizing MSCs and MSC-derived exosomes to improve islet engraftment and long-term function. Particular emphasis is placed on exosome engineering strategies—such as therapeutic cargo loading and targeted delivery—as well as encapsulation techniques that facilitate sustained release and graft protection. Despite encouraging preclinical results, the field remains in its early stages, and further research is required to standardize exosome isolation, elucidate mechanisms of action, and ensure clinical translatability. Harnessing the full potential of MSC-derived exosomes may offer a next-generation approach for achieving durable glycemic control and β-cell regeneration in T1DM.

胰岛移植是治疗1型糖尿病（T1DM）的一种有前景的治疗策略，但其临床应用受到胰岛分离、培养和移植后缺氧、氧化应激和免疫排斥的限制。近年来，间充质干细胞（MSCs）已被证明能够通过免疫调节、抗炎作用和旁分泌信号传导增强胰岛的存活和功能。在分泌的成分中，外泌体已成为MSC功能的关键介质，能够将核酸，蛋白质和脂质传递到具有高生物相容性和低免疫原性的靶细胞。本文综述了利用间充质干细胞和间充质干细胞衍生的外泌体改善胰岛移植和长期功能的最新进展。特别强调的是外泌体工程策略，如治疗货物装载和靶向递送，以及促进持续释放和移植物保护的封装技术。尽管临床前结果令人鼓舞，但该领域仍处于早期阶段，需要进一步的研究来规范外泌体的分离，阐明作用机制，并确保临床可翻译性。利用msc来源的外泌体的全部潜力可能为T1DM患者实现持久的血糖控制和β细胞再生提供新一代方法。

{"title":"Enhancing islet transplantation outcomes in T1DM: The promise of mesenchymal stem cells and exosomes","authors":"Ying Zhang , Xiaoyue Chen , Zhuoxun Huang , Yifan Qiu , Longfa Kou , Qing Yao","doi":"10.1016/j.ijpx.2026.100498","DOIUrl":"10.1016/j.ijpx.2026.100498","url":null,"abstract":"<div><div>Islet transplantation represents a promising therapeutic strategy for type 1 diabetes mellitus (T1DM), yet its clinical application is constrained by hypoxia, oxidative stress, and immune rejection during islet isolation, culture, and post-transplantation. In recent years, mesenchymal stem cells (MSCs) have demonstrated the ability to enhance islet survival and function through immunomodulation, anti-inflammatory effects, and paracrine signaling. Among the secreted components, exosomes have emerged as key mediators of MSC function, capable of delivering nucleic acids, proteins, and lipids to target cells with high biocompatibility and low immunogenicity. This review highlights recent advances in utilizing MSCs and MSC-derived exosomes to improve islet engraftment and long-term function. Particular emphasis is placed on exosome engineering strategies—such as therapeutic cargo loading and targeted delivery—as well as encapsulation techniques that facilitate sustained release and graft protection. Despite encouraging preclinical results, the field remains in its early stages, and further research is required to standardize exosome isolation, elucidate mechanisms of action, and ensure clinical translatability. Harnessing the full potential of MSC-derived exosomes may offer a next-generation approach for achieving durable glycemic control and β-cell regeneration in T1DM.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100498"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188934","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

Brain-targeted delivery of siRNA via non-viral delivery systems, the therapeutic strategy for Alzheimer's disease—Unveiling challenges and prospects 通过非病毒传递系统的siRNA脑靶向递送，阿尔茨海默病的治疗策略-揭示挑战和前景

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2026-06-01 Epub Date: 2026-02-05 DOI: 10.1016/j.ijpx.2026.100503

Lili Gu , Jiayi Liu , Can Wang , Xiaoqin Shan , Siyi Li , Xinyue Zhang , Lijie Xia , Jinyao Li

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive and behavioral issues, posing significant public health challenges. Small interfering RNAs (siRNAs) offer the potential to selectively silence AD-related pathogenic genes. This review first outlines the diverse pathogenic mechanisms and hallmark pathologies of AD, then spotlights the key genes now being silenced by siRNA for therapeutic intervention. These genes encompass those directly implicated in amyloidogenesis, tau phosphorylation, and neuroinflammation, along with those aberrantly up-regulated and associated with AD pathology. Finally, it summarizes recent research on non-viral and local siRNA delivery strategies including lipid, polymer, quantum dots, inorganic materials, extracellular vesicles, and conjugates aimed at effectively penetrating the blood-brain barrier while overcoming intra- and extracellular barriers to target key AD pathways. These findings underscore the promise of siRNA therapy in addressing AD pathology and provide valuable insights into overcoming delivery challenges.

阿尔茨海默病（AD）是一种以认知和行为问题为特征的神经退行性疾病，对公共卫生构成重大挑战。小干扰rna （sirna）提供了选择性沉默ad相关致病基因的潜力。本文首先概述了阿尔茨海默病的多种致病机制和标志性病理，然后重点介绍了目前被siRNA沉默用于治疗干预的关键基因。这些基因包括那些直接涉及淀粉样蛋白形成、tau磷酸化和神经炎症的基因，以及那些异常上调并与AD病理相关的基因。最后，总结了近年来关于非病毒和局部siRNA递送策略的研究，包括脂质、聚合物、量子点、无机材料、细胞外囊泡和偶联物，旨在有效穿透血脑屏障，同时克服细胞内和细胞外屏障，靶向AD关键通路。这些发现强调了siRNA疗法在解决AD病理方面的前景，并为克服递送挑战提供了有价值的见解。

{"title":"Brain-targeted delivery of siRNA via non-viral delivery systems, the therapeutic strategy for Alzheimer's disease—Unveiling challenges and prospects","authors":"Lili Gu , Jiayi Liu , Can Wang , Xiaoqin Shan , Siyi Li , Xinyue Zhang , Lijie Xia , Jinyao Li","doi":"10.1016/j.ijpx.2026.100503","DOIUrl":"10.1016/j.ijpx.2026.100503","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive and behavioral issues, posing significant public health challenges. Small interfering RNAs (siRNAs) offer the potential to selectively silence AD-related pathogenic genes. This review first outlines the diverse pathogenic mechanisms and hallmark pathologies of AD, then spotlights the key genes now being silenced by siRNA for therapeutic intervention. These genes encompass those directly implicated in amyloidogenesis, tau phosphorylation, and neuroinflammation, along with those aberrantly up-regulated and associated with AD pathology. Finally, it summarizes recent research on non-viral and local siRNA delivery strategies including lipid, polymer, quantum dots, inorganic materials, extracellular vesicles, and conjugates aimed at effectively penetrating the blood-brain barrier while overcoming intra- and extracellular barriers to target key AD pathways. These findings underscore the promise of siRNA therapy in addressing AD pathology and provide valuable insights into overcoming delivery challenges.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100503"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188935","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

Stabilization strategies and advancements in lyophilization to preserve integrity and efficacy of next-generation biologicals 冷冻干燥的稳定策略和进展，以保持下一代生物制品的完整性和有效性

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2026-06-01 Epub Date: 2026-05-26 DOI: 10.1016/j.ijpx.2026.100575

Ravi Maharjan , Chang Yell Shin , Seon-Kwang Lee , Eun-Sol Ha , Heejun Park , Jeong-Soo Kim , Ki Hyun Kim , Nam Ah. Kim , Min-Soo Kim , Seong Hoon Jeong

The success of mRNA-lipid nanoparticles (LNPs) vaccines during the COVID-19 pandemic has significantly increased global demand for stable, thermo-resistant biologicals. Lyophilization remains a cornerstone technology for enhancing the stability of these formulations; however, the freezing and drying processes impose major stresses that can compromise the integrity of fragile LNPs. This review systematically explores the molecular mechanisms by which lyoprotectants, including sugars, polyols, amino acids, and polymers, mitigate challenges such as ice-induced denaturation, dehydration-driven aggregation, and interfacial destabilization. This review emphasizes the importance of optimized sucrose-trehalose combinations and effective ice-nucleation control in preserving encapsulation efficiency and maintaining particle integrity. Furthermore, the review discusses advanced process optimization tools, including digital twin modeling and in-line Raman spectroscopy, which enhance lyophilization efficiency by reducing primary drying times by up to 40% while ensuring critical quality attributes are preserved. Additionally, emerging applications utilizing novel excipient combinations are highlighted, showcasing their potential to enable refrigerated storage of viral vectors. With 85% of commercial conjugates relying on lyophilization, recent advancements in continuous freeze-drying technology, such as spin-freeze approaches, have achieved cycle times that are three-fold faster. These developments provide a comprehensive roadmap for overcoming cold chain limitations while addressing the stabilization needs of next-generation biologicals, CRISPR-based systems, and personalized medicines.

在COVID-19大流行期间，mrna -脂质纳米颗粒（LNPs）疫苗的成功显著增加了全球对稳定、耐热生物制品的需求。冻干仍然是提高这些配方稳定性的基础技术；然而，冷冻和干燥过程施加的压力可能会损害脆弱的LNPs的完整性。这篇综述系统地探讨了冷冻保护剂的分子机制，包括糖、多元醇、氨基酸和聚合物，减轻了冰诱导的变性、脱水驱动的聚集和界面不稳定等挑战。本文强调了优化蔗糖-海藻糖组合和有效的冰核控制对保持包封效率和保持颗粒完整性的重要性。此外，该综述还讨论了先进的工艺优化工具，包括数字孪生模型和在线拉曼光谱，它们通过将初级干燥时间减少40%来提高冻干效率，同时确保关键的质量属性得以保留。此外，利用新型赋形剂组合的新兴应用被强调，展示了它们的潜力，使病毒载体的冷藏储存。85%的商业偶联物依赖于冻干，最近连续冷冻干燥技术的进步，如自旋冷冻方法，已经实现了三倍快的循环时间。这些发展为克服冷链限制提供了全面的路线图，同时解决了下一代生物制品、基于crispr的系统和个性化药物的稳定需求。

{"title":"Stabilization strategies and advancements in lyophilization to preserve integrity and efficacy of next-generation biologicals","authors":"Ravi Maharjan , Chang Yell Shin , Seon-Kwang Lee , Eun-Sol Ha , Heejun Park , Jeong-Soo Kim , Ki Hyun Kim , Nam Ah. Kim , Min-Soo Kim , Seong Hoon Jeong","doi":"10.1016/j.ijpx.2026.100575","DOIUrl":"10.1016/j.ijpx.2026.100575","url":null,"abstract":"<div><div>The success of mRNA-lipid nanoparticles (LNPs) vaccines during the COVID-19 pandemic has significantly increased global demand for stable, thermo-resistant biologicals. Lyophilization remains a cornerstone technology for enhancing the stability of these formulations; however, the freezing and drying processes impose major stresses that can compromise the integrity of fragile LNPs. This review systematically explores the molecular mechanisms by which lyoprotectants, including sugars, polyols, amino acids, and polymers, mitigate challenges such as ice-induced denaturation, dehydration-driven aggregation, and interfacial destabilization. This review emphasizes the importance of optimized sucrose-trehalose combinations and effective ice-nucleation control in preserving encapsulation efficiency and maintaining particle integrity. Furthermore, the review discusses advanced process optimization tools, including digital twin modeling and in-line Raman spectroscopy, which enhance lyophilization efficiency by reducing primary drying times by up to 40% while ensuring critical quality attributes are preserved. Additionally, emerging applications utilizing novel excipient combinations are highlighted, showcasing their potential to enable refrigerated storage of viral vectors. With 85% of commercial conjugates relying on lyophilization, recent advancements in continuous freeze-drying technology, such as spin-freeze approaches, have achieved cycle times that are three-fold faster. These developments provide a comprehensive roadmap for overcoming cold chain limitations while addressing the stabilization needs of next-generation biologicals, CRISPR-based systems, and personalized medicines.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100575"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148184151","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

Data-efficient prediction in tableting using word embeddings and empirically-guided neural networks 使用词嵌入和经验引导神经网络的数据高效预测

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2026-06-01 Epub Date: 2025-12-03 DOI: 10.1016/j.ijpx.2025.100458

Najeeb Abdelrahman, Stefan Klinken-Uth

The development of robust oral tablet formulations remains time-consuming, often limited by scarce data and the difficulty of incorporating categorical formulation variables into predictive models. Traditional regression methods are interpretable but struggle with nonlinear interactions, whereas modern machine learning approaches offer higher predictive power at the expense of transparency. In this study, we present a neural network framework that employs word embedding layers to represent categorical formulation factors, such as active pharmaceutical ingredients (APIs), as trainable semantic vectors. These embeddings are integrated with empirically-guided output functions and a deep ensemble strategy to predict tablet quality attributes, including tensile strength and density as well as ejection force, and dosing height, based solely on formulation composition, compression pressure, and tablet weight. The model achieved predictive accuracy comparable to or exceeding classical regression while reliably avoiding physically implausible outputs. Analysis of the learned embedding vectors revealed meaningful clustering of APIs, enabling transfer learning across materials and robust predictions even for APIs with few or no training data. Furthermore, information gain analysis demonstrated that low-concentration formulations can substantially enhance predictive accuracy, supporting more material-efficient experimental designs. These results highlight embedding-based, empirically-guided neural networks as explainable and practical tools that could accelerate pharmaceutical formulation development in the future.

强大的口服片剂配方的开发仍然耗时，往往受到数据稀缺和将分类配方变量纳入预测模型的困难的限制。传统的回归方法是可解释的，但与非线性相互作用作斗争，而现代机器学习方法以牺牲透明度为代价提供了更高的预测能力。在这项研究中，我们提出了一个神经网络框架，该框架使用词嵌入层来表示分类配方因素，如活性药物成分（api），作为可训练的语义向量。这些嵌入集成了经验导向的输出函数和深度集成策略，以预测片剂的质量属性，包括抗拉强度和密度，以及弹射力和剂量高度，仅基于配方成分，压缩压力和片剂重量。该模型达到了与经典回归相当或超过经典回归的预测精度，同时可靠地避免了物理上不合理的输出。对学习到的嵌入向量的分析揭示了api的有意义的聚类，实现了跨材料的迁移学习和即使只有很少或没有训练数据的api的鲁棒预测。此外，信息增益分析表明，低浓度配方可以大大提高预测精度，支持更高效的实验设计。这些结果突出了基于嵌入的、经验指导的神经网络作为可解释和实用的工具，可以加速未来的药物配方开发。

{"title":"Data-efficient prediction in tableting using word embeddings and empirically-guided neural networks","authors":"Najeeb Abdelrahman, Stefan Klinken-Uth","doi":"10.1016/j.ijpx.2025.100458","DOIUrl":"10.1016/j.ijpx.2025.100458","url":null,"abstract":"<div><div>The development of robust oral tablet formulations remains time-consuming, often limited by scarce data and the difficulty of incorporating categorical formulation variables into predictive models. Traditional regression methods are interpretable but struggle with nonlinear interactions, whereas modern machine learning approaches offer higher predictive power at the expense of transparency. In this study, we present a neural network framework that employs word embedding layers to represent categorical formulation factors, such as active pharmaceutical ingredients (APIs), as trainable semantic vectors. These embeddings are integrated with empirically-guided output functions and a deep ensemble strategy to predict tablet quality attributes, including tensile strength and density as well as ejection force, and dosing height, based solely on formulation composition, compression pressure, and tablet weight. The model achieved predictive accuracy comparable to or exceeding classical regression while reliably avoiding physically implausible outputs. Analysis of the learned embedding vectors revealed meaningful clustering of APIs, enabling transfer learning across materials and robust predictions even for APIs with few or no training data. Furthermore, information gain analysis demonstrated that low-concentration formulations can substantially enhance predictive accuracy, supporting more material-efficient experimental designs. These results highlight embedding-based, empirically-guided neural networks as explainable and practical tools that could accelerate pharmaceutical formulation development in the future.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100458"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977954","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

Nanoparticle carriers in the treatment of intracellular bacterial infections: Current approaches and challenges 纳米颗粒载体治疗细胞内细菌感染：目前的方法和挑战

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2026-06-01 Epub Date: 2026-05-20 DOI: 10.1016/j.ijpx.2026.100574

Zheng Lu , Bin He , Zhixin Lei , Lijun Wu , Dongyang Ye , Dan Xu , Shanqin Chen , Xiaotian Zhang , Ziqi Weng

Pathogenic bacterial intracellular infection by Mycobacterium tuberculosis and Staphylococcus aureus is a major complication to treatment because of resistance to immune actions and the ability to withstand traditional antibiotics. Failure of existing therapies is usually due to inefficient intracellular penetration of drugs and inappropriate targeting of subcellular sites. We discuss the nanoparticle drug delivery systems (NDDSs) here that enhance intracellular delivery of antibiotics using customized carrier materials, targeted internalization processes and stimuli-responsive release of antibiotics. These systems enhance specificity of pathogen targeting and efficacy of drugs and overcome barriers of microenvironment. We also address translational challenges such as toxicity, heterogeneity of infection, scalability of manufacturing, and scanty clinical data. Future trends include versatile hybrid vehicles, combination with immunomodulators or gene-editing applications and AI-enhanced personalized nanomedicine. The potential to tackle pathogen-specific issues with nanotechnology advances can provide possible solutions to the treatment of persistent intracellular infections and antibiotic resistance, which are the prospects with NDDSs.

由结核分枝杆菌和金黄色葡萄球菌引起的致病性细菌细胞内感染是治疗的主要并发症，因为它们对免疫作用有抵抗力，并且能够抵抗传统抗生素。现有疗法的失败通常是由于药物在细胞内渗透效率低下和亚细胞部位靶向不当。我们在这里讨论纳米颗粒药物递送系统（ndds），该系统使用定制的载体材料、靶向内化过程和抗生素的刺激反应释放来增强抗生素的细胞内递送。这些系统提高了病原体靶向的特异性和药物的有效性，克服了微环境的障碍。我们还解决了翻译方面的挑战，如毒性、感染的异质性、生产的可扩展性和缺乏临床数据。未来的趋势包括多用途混合动力汽车，与免疫调节剂或基因编辑应用的结合，以及人工智能增强的个性化纳米医学。利用纳米技术进步解决病原体特异性问题的潜力可以为治疗持续性细胞内感染和抗生素耐药性提供可能的解决方案，这是NDDSs的前景。

{"title":"Nanoparticle carriers in the treatment of intracellular bacterial infections: Current approaches and challenges","authors":"Zheng Lu , Bin He , Zhixin Lei , Lijun Wu , Dongyang Ye , Dan Xu , Shanqin Chen , Xiaotian Zhang , Ziqi Weng","doi":"10.1016/j.ijpx.2026.100574","DOIUrl":"10.1016/j.ijpx.2026.100574","url":null,"abstract":"<div><div>Pathogenic bacterial intracellular infection by <em>Mycobacterium tuberculosis</em> and <em>Staphylococcus aureus</em> is a major complication to treatment because of resistance to immune actions and the ability to withstand traditional antibiotics. Failure of existing therapies is usually due to inefficient intracellular penetration of drugs and inappropriate targeting of subcellular sites. We discuss the nanoparticle drug delivery systems (NDDSs) here that enhance intracellular delivery of antibiotics using customized carrier materials, targeted internalization processes and stimuli-responsive release of antibiotics. These systems enhance specificity of pathogen targeting and efficacy of drugs and overcome barriers of microenvironment. We also address translational challenges such as toxicity, heterogeneity of infection, scalability of manufacturing, and scanty clinical data. Future trends include versatile hybrid vehicles, combination with immunomodulators or gene-editing applications and AI-enhanced personalized nanomedicine. The potential to tackle pathogen-specific issues with nanotechnology advances can provide possible solutions to the treatment of persistent intracellular infections and antibiotic resistance, which are the prospects with NDDSs.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100574"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148184152","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

Improving the bioavailability of nintedanib by formulating inhalable ufasomes as a targeted therapy for non-small cell lung cancer 提高尼达尼布的生物利用度，通过制定可吸入的非小细胞肺癌的靶向治疗

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2026-06-01 Epub Date: 2025-12-30 DOI: 10.1016/j.ijpx.2025.100482

Salman M. Ghazwani , Sami Alhazmi , Salhah M. Ghazwani , Hussam M. Shubaily , Ahmed M. Wafi , Naifa Alenazi , Marwa Qadri , Amal Naif Alshammari , Wedad Mawkili , Jobran M. Moshi , Zenat Khired , Salama A. Salama

The safety and effectiveness of nintedanib in treating non-small cell lung cancer (NSCLC) have been evaluated in several clinical trials. However, nintedanib exhibits low oral bioavailability due to its poor solubility and first-pass metabolism. To enhance the sustainability, targeting, bioavailability, and effectiveness of nintedanib, a targeted therapy for NSCLC was developed in the form of nebulized nintedanib ufasomes (NLU). Various NLU formulations were optimized utilizing the Design Expert software. The selected NLU was then evaluated for its aerodynamics, cytotoxicity, bioavailability, and targeting capabilities. To evaluate the effectiveness and safety of the optimal NLU formulation, a dose-dependent study was conducted using a mouse model of lung cancer induced by Lewis lung carcinoma (LLC) cell lines. The selected NLU formulation increased the sustainability, bioavailability, and targeting capability of nintedanib by 49.5 %, 6.63-fold, and 8.99-fold, respectively. Additionally, it decreased the IC₅₀ value by 4.7-fold. The nebulized NLU showed better anti-tumor, anti-inflammatory, and anti-oxidative effects than oral nintedanib in terms of LDH, CEA, AFP, MDA, TNF-α, and IL-1β. The histopathological analysis confirmed these results. The safety and efficacy studies demonstrated that the nebulized NLU formulation at a dose of 100 mg/kg could serve as a viable therapy for NSCLC.

尼达尼布治疗非小细胞肺癌（NSCLC）的安全性和有效性已在多个临床试验中得到评价。然而，尼达尼布由于其溶解度和首次代谢较差，口服生物利用度较低。为了提高尼达尼布的可持续性、靶向性、生物利用度和有效性，一种以雾化尼达尼布素（NLU）形式的非小细胞肺癌靶向治疗被开发出来。利用Design Expert软件对各种NLU配方进行了优化。然后对选定的NLU进行空气动力学、细胞毒性、生物利用度和靶向能力的评估。为了评价最佳NLU配方的有效性和安全性，采用Lewis肺癌（LLC）细胞系诱导的小鼠肺癌模型进行了剂量依赖性研究。选择的NLU配方使尼达尼布的可持续性、生物利用度和靶向性分别提高了49.5%、6.63倍和8.99倍。此外，IC50值降低了4.7倍。在LDH、CEA、AFP、MDA、TNF-α、IL-1β等指标上，NLU雾化组的抗肿瘤、抗炎、抗氧化作用优于口服尼达尼布。组织病理学分析证实了这些结果。安全性和有效性研究表明，雾化NLU制剂剂量为100mg /kg，可作为一种可行的治疗NSCLC的方法。

{"title":"Improving the bioavailability of nintedanib by formulating inhalable ufasomes as a targeted therapy for non-small cell lung cancer","authors":"Salman M. Ghazwani , Sami Alhazmi , Salhah M. Ghazwani , Hussam M. Shubaily , Ahmed M. Wafi , Naifa Alenazi , Marwa Qadri , Amal Naif Alshammari , Wedad Mawkili , Jobran M. Moshi , Zenat Khired , Salama A. Salama","doi":"10.1016/j.ijpx.2025.100482","DOIUrl":"10.1016/j.ijpx.2025.100482","url":null,"abstract":"<div><div>The safety and effectiveness of nintedanib in treating non-small cell lung cancer (NSCLC) have been evaluated in several clinical trials. However, nintedanib exhibits low oral bioavailability due to its poor solubility and first-pass metabolism. To enhance the sustainability, targeting, bioavailability, and effectiveness of nintedanib, a targeted therapy for NSCLC was developed in the form of nebulized nintedanib ufasomes (NLU). Various NLU formulations were optimized utilizing the Design Expert software. The selected NLU was then evaluated for its aerodynamics, cytotoxicity, bioavailability, and targeting capabilities. To evaluate the effectiveness and safety of the optimal NLU formulation, a dose-dependent study was conducted using a mouse model of lung cancer induced by Lewis lung carcinoma (LLC) cell lines. The selected NLU formulation increased the sustainability, bioavailability, and targeting capability of nintedanib by 49.5 %, 6.63-fold, and 8.99-fold, respectively. Additionally, it decreased the IC<sub>50</sub> value by 4.7-fold. The nebulized NLU showed better anti-tumor, anti-inflammatory, and anti-oxidative effects than oral nintedanib in terms of LDH, CEA, AFP, MDA, TNF-α, and IL-1β. The histopathological analysis confirmed these results. The safety and efficacy studies demonstrated that the nebulized NLU formulation at a dose of 100 mg/kg could serve as a viable therapy for NSCLC.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100482"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034577","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

Can therapeutic potency of a cancer nanomedicine be predicted by pain-related behavioral test in subcutaneous tumor model? 皮下肿瘤模型疼痛相关行为测试能否预测纳米肿瘤药物的治疗效果？

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2026-06-01 Epub Date: 2025-11-17 DOI: 10.1016/j.ijpx.2025.100450

Ye Tao , Xiaohui Cai , Zhongping Chen

Cancer nanomedicines have shown great potential in fighting against cancer. While the development of cancer nanomedicines is advancing rapidly, preclinical assessment approaches for their therapeutic potency have stagnated. In view of high prevalence of cancer pain in cancer patients, we aim to determine whether therapeutic potency of a cancer nanomedicine can be predicted by pain-related behavioral test in subcutaneous tumor model, the simplest and most widely used tumor model in oncology. Behavioral profiles reveal that subcutaneous tumor, probably irrespective of tumor type, presents with spontaneous pain (open field test) and evoked pain (von Frey test for mechanical allodynia; Hargreaves test, hot plate test, and tail flick test for thermal hyperalgesia; cold plate test and acetone drop test for thermal allodynia). Using doxorubicin (DOX)-loaded lipid nanoparticles (LNPs) (LNPs/DOX) as a representative cancer nanomedicine and ropivacaine (ROP)-loaded LNPs (LNPs/ROP) as a pain nanomedicine, it is validated that inhibiting subcutaneous tumor growth can relieve cancer pain, while delaying the growth cannot, despite a significant difference found compared with non-treatment group. Moreover, behavioral results in all the tests are consistent and von Frey test is suggested the most sensitive among them. It is strongly suggested that pain-related behavioral test can serve as a powerful tool to predict therapeutic potency of a cancer nanomedicine in vivo in treating subcutaneous tumor.

纳米抗癌药物在抗癌方面显示出巨大的潜力。虽然癌症纳米药物的发展正在迅速推进，但对其治疗效力的临床前评估方法却停滞不前。鉴于癌症患者中癌性疼痛的高发性，我们的目的是通过肿瘤模型中最简单、应用最广泛的肿瘤模型——皮下肿瘤模型的疼痛相关行为测试，来确定一种癌症纳米药物的治疗效力是否可以预测。行为特征显示皮下肿瘤，可能与肿瘤类型无关，表现为自发性疼痛（开场试验）和诱发性疼痛（von Frey机械异常痛试验；Hargreaves热痛觉过敏试验、热板试验和甩尾试验；热异常痛冷板试验和丙酮滴试验）。以阿霉素（DOX）负载脂质纳米颗粒（LNPs/DOX）为代表的肿瘤纳米药物，以罗哌卡因（ROP）负载的LNPs （LNPs/ROP）为代表的疼痛纳米药物，验证了抑制皮下肿瘤生长可以缓解癌症疼痛，而延迟生长则不能，尽管与未治疗组相比有显著差异。此外，所有测试的行为结果都是一致的，其中von Frey测试被认为是最敏感的。提示疼痛相关行为测试可作为预测肿瘤纳米药物在体内治疗皮下肿瘤疗效的有力工具。

{"title":"Can therapeutic potency of a cancer nanomedicine be predicted by pain-related behavioral test in subcutaneous tumor model?","authors":"Ye Tao , Xiaohui Cai , Zhongping Chen","doi":"10.1016/j.ijpx.2025.100450","DOIUrl":"10.1016/j.ijpx.2025.100450","url":null,"abstract":"<div><div>Cancer nanomedicines have shown great potential in fighting against cancer. While the development of cancer nanomedicines is advancing rapidly, preclinical assessment approaches for their therapeutic potency have stagnated. In view of high prevalence of cancer pain in cancer patients, we aim to determine whether therapeutic potency of a cancer nanomedicine can be predicted by pain-related behavioral test in subcutaneous tumor model, the simplest and most widely used tumor model in oncology. Behavioral profiles reveal that subcutaneous tumor, probably irrespective of tumor type, presents with spontaneous pain (open field test) and evoked pain (von Frey test for mechanical allodynia; Hargreaves test, hot plate test, and tail flick test for thermal hyperalgesia; cold plate test and acetone drop test for thermal allodynia). Using doxorubicin (DOX)-loaded lipid nanoparticles (LNPs) (LNPs/DOX) as a representative cancer nanomedicine and ropivacaine (ROP)-loaded LNPs (LNPs/ROP) as a pain nanomedicine, it is validated that inhibiting subcutaneous tumor growth can relieve cancer pain, while delaying the growth cannot, despite a significant difference found compared with non-treatment group. Moreover, behavioral results in all the tests are consistent and von Frey test is suggested the most sensitive among them. It is strongly suggested that pain-related behavioral test can serve as a powerful tool to predict therapeutic potency of a cancer nanomedicine <em>in vivo</em> in treating subcutaneous tumor.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100450"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921846","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