Pub Date : 2024-10-01DOI: 10.1016/j.ajps.2024.100953
Jung Suk Kim , Seunghyun Cheon , Mi Ran Woo , Sanghyun Woo , Jee-Eun Chung , Yu Seok Youn , Kyung Taek Oh , Soo-Jeong Lim , Sae Kwang Ku , Bao Loc Nguyen , Jong Oh Kim , Sung Giu Jin , Han-Gon Choi
While spray-drying has been widely utilized to improve the bioavailability of poorly water-soluble drugs, the outcomes often exhibit suboptimal particle size distribution and large particle sizes, limiting their effectiveness. In this study, we introduce electrostatic spraying as an advanced technology tailored for poorly water-soluble drugs, enabling the fabrication of nanoparticles with fine and uniform particle size distribution. Regorafenib (1 g), as a model drug, copovidone (5 g), and sodium dodecyl sulfate (0.1 g) were dissolved in 200 ml ethanol and subjected to conventional-spray-dryer and electrostatic spray dryer. The electrostatic spray-dried nanoparticles (ESDN) showed smaller particle sizes with better uniformity compared to conventional spray-dried nanoparticles (CSDN). ESDN demonstrated significantly enhanced solubility and rapid release in water. In vitro studies revealed that ESDN induced apoptosis in HCT-116 cells to a greater extent, exhibiting superior cytotoxicity compared to CSDN. Furthermore, ESDN substantially improved oral bioavailability and antitumor efficacy compared to CSDN. These findings suggest that ESD shows potential in developing enhanced drug delivery systems for poorly water-soluble drugs, effectively addressing the limitations associated with CSD methods.
{"title":"Electrostatic spraying for fine-tuning particle dimensions to enhance oral bioavailability of poorly water-soluble drugs","authors":"Jung Suk Kim , Seunghyun Cheon , Mi Ran Woo , Sanghyun Woo , Jee-Eun Chung , Yu Seok Youn , Kyung Taek Oh , Soo-Jeong Lim , Sae Kwang Ku , Bao Loc Nguyen , Jong Oh Kim , Sung Giu Jin , Han-Gon Choi","doi":"10.1016/j.ajps.2024.100953","DOIUrl":"10.1016/j.ajps.2024.100953","url":null,"abstract":"<div><div>While spray-drying has been widely utilized to improve the bioavailability of poorly water-soluble drugs, the outcomes often exhibit suboptimal particle size distribution and large particle sizes, limiting their effectiveness. In this study, we introduce electrostatic spraying as an advanced technology tailored for poorly water-soluble drugs, enabling the fabrication of nanoparticles with fine and uniform particle size distribution. Regorafenib (1 g), as a model drug, copovidone (5 g), and sodium dodecyl sulfate (0.1 g) were dissolved in 200 ml ethanol and subjected to conventional-spray-dryer and electrostatic spray dryer. The electrostatic spray-dried nanoparticles (ESDN) showed smaller particle sizes with better uniformity compared to conventional spray-dried nanoparticles (CSDN). ESDN demonstrated significantly enhanced solubility and rapid release in water. <em>In vitro</em> studies revealed that ESDN induced apoptosis in HCT-116 cells to a greater extent, exhibiting superior cytotoxicity compared to CSDN. Furthermore, ESDN substantially improved oral bioavailability and antitumor efficacy compared to CSDN. These findings suggest that ESD shows potential in developing enhanced drug delivery systems for poorly water-soluble drugs, effectively addressing the limitations associated with CSD methods.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 5","pages":"Article 100953"},"PeriodicalIF":10.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142191684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.ajps.2024.100949
Cong Li , Kexin Zhang , Zehua Cheng , Lihong Wang , Zehao Li , Chao Shen , Zhihang Li , Zeyu Wang , Lianrui Cao , Lijiang Chen
Tumor metastasis is responsible for 90 % of cancer-associated deaths, and its early detection may decrease the likelihood of mortality. Studies have demonstrated that metastasis results from the interaction between “seeds” (tumor cells) and “soil” (pre-metastatic niche, PMN). As the first and most abundant immune cells to be recruited to PMN, neutrophils play a key role in the ultimate formation of metastatic foci through mechanisms such as supporting tumor cell growth, promoting angiogenesis, and shaping an immune-suppressive microenvironment. In this study, two distinct types of sialic acid (SA)-modified liposomes were prepared to target and regulate pro-metastatic neutrophils through the l-selectin receptor. One of these liposomes, named ICG@SAL, was used to encapsulate indocyanine green (ICG) and was specifically designed for the early detection of cancer metastasis. The other liposome, referred to as ABE/Cur@SAL, co-loaded abemaciclib (ABE) and curcumin (Cur), with the intention of suppressing the progression of metastatic tumor. Fluorescence imaging results from the mouse spontaneous metastasis model indicated that ICG@SAL demonstrated faster targeting and stronger accumulation in the metastatic organs than unmodified ICG liposomes (ICG@CL). This suggested that ICG@SAL could detect tumor metastasis at an early stage. The therapy with co-loaded liposomes in the mouse experimental lung metastasis model indicated that ABE/Cur@SAL could inhibit regulatory T (Treg) cell proliferation, enhance effector T cell activity and reduce tumorigenic factor release, implying that ABE/Cur@SAL could inhibit tumor metastasis. Overall, our work provided a sensitive and convenient approach to early diagnosis and treatment of tumor metastasis. ICG@SAL could be employed for the early detection of tumor metastasis, while ABE/Cur@SAL could be used to inhibit the development of tumor metastasis when early metastasis was identified.
{"title":"Neutrophil-targeted liposomal platform: A shift in novel approach for early detection and treatment of cancer metastasis","authors":"Cong Li , Kexin Zhang , Zehua Cheng , Lihong Wang , Zehao Li , Chao Shen , Zhihang Li , Zeyu Wang , Lianrui Cao , Lijiang Chen","doi":"10.1016/j.ajps.2024.100949","DOIUrl":"10.1016/j.ajps.2024.100949","url":null,"abstract":"<div><div>Tumor metastasis is responsible for 90 % of cancer-associated deaths, and its early detection may decrease the likelihood of mortality. Studies have demonstrated that metastasis results from the interaction between “seeds” (tumor cells) and “soil” (pre-metastatic niche, PMN). As the first and most abundant immune cells to be recruited to PMN, neutrophils play a key role in the ultimate formation of metastatic foci through mechanisms such as supporting tumor cell growth, promoting angiogenesis, and shaping an immune-suppressive microenvironment. In this study, two distinct types of sialic acid (SA)-modified liposomes were prepared to target and regulate pro-metastatic neutrophils through the <em>l</em>-selectin receptor. One of these liposomes, named ICG@SAL, was used to encapsulate indocyanine green (ICG) and was specifically designed for the early detection of cancer metastasis. The other liposome, referred to as ABE/Cur@SAL, co-loaded abemaciclib (ABE) and curcumin (Cur), with the intention of suppressing the progression of metastatic tumor. Fluorescence imaging results from the mouse spontaneous metastasis model indicated that ICG@SAL demonstrated faster targeting and stronger accumulation in the metastatic organs than unmodified ICG liposomes (ICG@CL). This suggested that ICG@SAL could detect tumor metastasis at an early stage. The therapy with co-loaded liposomes in the mouse experimental lung metastasis model indicated that ABE/Cur@SAL could inhibit regulatory T (Treg) cell proliferation, enhance effector T cell activity and reduce tumorigenic factor release, implying that ABE/Cur@SAL could inhibit tumor metastasis. Overall, our work provided a sensitive and convenient approach to early diagnosis and treatment of tumor metastasis. ICG@SAL could be employed for the early detection of tumor metastasis, while ABE/Cur@SAL could be used to inhibit the development of tumor metastasis when early metastasis was identified.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 5","pages":"Article 100949"},"PeriodicalIF":10.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142191724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.ajps.2024.100954
Huiwen Zhang , Wanqi Zhu , Wei Pan , Xiuyan Wan , Na Li , Bo Tang
Malignant glioma remains one of the most aggressive intracranial tumors with devastating clinical outcomes despite the great advances in conventional treatment approaches, including surgery and chemotherapy. Spatio-temporally controllable approaches to glioma are now being actively investigated due to the preponderance, including spatio-temporal adjustability, minimally invasive, repetitive properties, etc. External stimuli can be readily controlled by adjusting the site and density of stimuli to exert the cytotoxic on glioma tissue and avoid undesired injury to normal tissues. It is worth noting that the removability of external stimuli allows for on-demand treatment, which effectively reduces the occurrence of side effects. In this review, we highlight recent advancements in drug delivery systems for spatio-temporally controllable treatments of glioma, focusing on the mechanisms and design principles of sensitizers utilized in these controllable therapies. Moreover, the potential challenges regarding spatio-temporally controllable therapy for glioma are also described, aiming to provide insights into future advancements in this field and their potential clinical applications.
{"title":"Recent advances in spatio-temporally controllable systems for management of glioma","authors":"Huiwen Zhang , Wanqi Zhu , Wei Pan , Xiuyan Wan , Na Li , Bo Tang","doi":"10.1016/j.ajps.2024.100954","DOIUrl":"10.1016/j.ajps.2024.100954","url":null,"abstract":"<div><div>Malignant glioma remains one of the most aggressive intracranial tumors with devastating clinical outcomes despite the great advances in conventional treatment approaches, including surgery and chemotherapy. Spatio-temporally controllable approaches to glioma are now being actively investigated due to the preponderance, including spatio-temporal adjustability, minimally invasive, repetitive properties, etc. External stimuli can be readily controlled by adjusting the site and density of stimuli to exert the cytotoxic on glioma tissue and avoid undesired injury to normal tissues. It is worth noting that the removability of external stimuli allows for on-demand treatment, which effectively reduces the occurrence of side effects. In this review, we highlight recent advancements in drug delivery systems for spatio-temporally controllable treatments of glioma, focusing on the mechanisms and design principles of sensitizers utilized in these controllable therapies. Moreover, the potential challenges regarding spatio-temporally controllable therapy for glioma are also described, aiming to provide insights into future advancements in this field and their potential clinical applications.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 5","pages":"Article 100954"},"PeriodicalIF":10.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142191682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.ajps.2024.100951
Aun Raza , Wei Wu
Metal-organic frameworks (MOFs) offer innovative solutions to the limitations of traditional oral drug delivery systems through their unique combination of metal ions and organic ligands. This review systematically examines the structural properties and principles of MOFs, setting the stage for their application in drug delivery. It discusses various classes of MOFs, including those based on zirconium, iron, zinc, copper, titanium, aluminum, potassium, and magnesium, assessing their drug-loading capacities, biocompatibility, and controlled release mechanisms. The effectiveness of MOFs is illustrated through case studies that highlight their capabilities in enhancing drug solubility, providing protection against the harsh gastrointestinal environment, and enabling precise drug release. The review addresses potential challenges, particularly the toxicity concerns associated with MOFs, and calls for further research into their biocompatibility and interactions with biological systems. It concludes by emphasizing the potential of MOFs in revolutionizing oral drug delivery, highlighting the critical need for comprehensive research to harness their full potential in clinical applications.
{"title":"Metal-organic frameworks in oral drug delivery","authors":"Aun Raza , Wei Wu","doi":"10.1016/j.ajps.2024.100951","DOIUrl":"10.1016/j.ajps.2024.100951","url":null,"abstract":"<div><div>Metal-organic frameworks (MOFs) offer innovative solutions to the limitations of traditional oral drug delivery systems through their unique combination of metal ions and organic ligands. This review systematically examines the structural properties and principles of MOFs, setting the stage for their application in drug delivery. It discusses various classes of MOFs, including those based on zirconium, iron, zinc, copper, titanium, aluminum, potassium, and magnesium, assessing their drug-loading capacities, biocompatibility, and controlled release mechanisms. The effectiveness of MOFs is illustrated through case studies that highlight their capabilities in enhancing drug solubility, providing protection against the harsh gastrointestinal environment, and enabling precise drug release. The review addresses potential challenges, particularly the toxicity concerns associated with MOFs, and calls for further research into their biocompatibility and interactions with biological systems. It concludes by emphasizing the potential of MOFs in revolutionizing oral drug delivery, highlighting the critical need for comprehensive research to harness their full potential in clinical applications.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 5","pages":"Article 100951"},"PeriodicalIF":10.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142191722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.ajps.2024.100955
Dawei Jiang , Chao Chen , Peng Dai , Caiyan Li , Zhiyi Feng , Na Dong , Fenzan Wu , Junpeng Xu , Ping Wu , Liuxi Chu , Shengcun Li , Xiaokun Li , Youjun Yang , Weian Zhang , Zhouguang Wang
The cyanine dyes represented by IR780 can achieve synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) under the stimulation of near-infrared (NIR) light (commonly 808 nm). Unfortunately, the stability of NIR-excited cyanine dyes is not satisfactory. These cyanine dyes can be attacked by self-generated reactive oxygen species (ROS) during PDT processes, resulting in structural damage and rapid degradation, which is fatal for phototherapy. To address this issue, a novel non-cyanine dye (IR890) was elaborately designed and synthesized by our team. The maximum absorption wavelength of IR890 was located in the deep NIR region (ca. 890 nm), which was beneficial for further improving tissue penetration depth. Importantly, IR890 exhibited good stability when continuously illuminated by deep NIR light. To improve the hydrophilicity and biocompatibility, the hydrophobic IR890 dye was grafted onto the side chain of hydrophilic polymer (POEGMA-b-PGMA-g-CCH) via click chemistry. Then, the synthesized POEGMA-b-PGMA-g-IR890 amphiphilic polymer was utilized to prepare P-IR890 nano-photosensitizer via self-assembly method. Under irradiation with deep NIR light (850 nm, 0.5 W/cm2, 10 min), the dye degradation rate of P-IR890 was less than 5%. However, IR780 was almost completely degraded with the same light output power density and irradiation duration. In addition, P-IR890 could stably generate a large number of ROS and heat at the same time. It was rarely reported that the stable synergistic combination therapy of PDT and PTT could be efficiently performed by a single photosensitizer via irradiation with deep NIR light. P-IR890 exhibited favorable anti-tumor outcomes through apoptosis pathway. Therefore, the P-IR890 could provide a new insight into the design of photosensitizers and new opportunities for synergistic combination therapy of PDT and PTT.
{"title":"Deep near infrared light-excited stable synergistic photodynamic and photothermal therapies based on P-IR890 nano-photosensitizer constructed via a non-cyanine dye","authors":"Dawei Jiang , Chao Chen , Peng Dai , Caiyan Li , Zhiyi Feng , Na Dong , Fenzan Wu , Junpeng Xu , Ping Wu , Liuxi Chu , Shengcun Li , Xiaokun Li , Youjun Yang , Weian Zhang , Zhouguang Wang","doi":"10.1016/j.ajps.2024.100955","DOIUrl":"10.1016/j.ajps.2024.100955","url":null,"abstract":"<div><div>The cyanine dyes represented by IR780 can achieve synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) under the stimulation of near-infrared (NIR) light (commonly 808 nm). Unfortunately, the stability of NIR-excited cyanine dyes is not satisfactory. These cyanine dyes can be attacked by self-generated reactive oxygen species (ROS) during PDT processes, resulting in structural damage and rapid degradation, which is fatal for phototherapy. To address this issue, a novel non-cyanine dye (IR890) was elaborately designed and synthesized by our team. The maximum absorption wavelength of IR890 was located in the deep NIR region (<em>ca.</em> 890 nm), which was beneficial for further improving tissue penetration depth. Importantly, IR890 exhibited good stability when continuously illuminated by deep NIR light. To improve the hydrophilicity and biocompatibility, the hydrophobic IR890 dye was grafted onto the side chain of hydrophilic polymer (POEGMA-b-PGMA-g-C<img>CH) <em>via</em> click chemistry. Then, the synthesized POEGMA-<em>b</em>-PGMA-<em>g</em>-IR890 amphiphilic polymer was utilized to prepare P-IR890 nano-photosensitizer <em>via</em> self-assembly method. Under irradiation with deep NIR light (850 nm, 0.5 W/cm<sup>2</sup>, 10 min), the dye degradation rate of P-IR890 was less than 5%. However, IR780 was almost completely degraded with the same light output power density and irradiation duration. In addition, P-IR890 could stably generate a large number of ROS and heat at the same time. It was rarely reported that the stable synergistic combination therapy of PDT and PTT could be efficiently performed by a single photosensitizer <em>via</em> irradiation with deep NIR light. P-IR890 exhibited favorable anti-tumor outcomes through apoptosis pathway. Therefore, the P-IR890 could provide a new insight into the design of photosensitizers and new opportunities for synergistic combination therapy of PDT and PTT.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 5","pages":"Article 100955"},"PeriodicalIF":10.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142191683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.ajps.2024.100948
Xinghua Ren , Xinyi Luo , Fuchang Wang , Long Wan , Xiaofan Wang , Jinya Xiong , Mengwei Ye , Shiqiao Rui , Zhu Liu , Siling Wang , Qinfu Zhao
As the third essential trace element in the human body, copper plays a crucial role in various physiological processes, which lays the foundation for its broad applications in cancer treatments. The overview of copper, including pharmacokinetics, signaling pathways, and homeostasis dysregulation, is hereby discussed. Additionally, cuproptosis, as a newly proposed cell death mechanism associated with copper accumulation, is analyzed and further developed for efficient cancer treatment. Different forms of Cu-based nanoparticles and their advantages, as well as limiting factors, are introduced. Moreover, the unique characteristics of Cu-based nanoparticles give rise to their applications in various imaging modalities. In addition, Cu-based nanomaterials are featured by their excellent photothermal property and ROS-associated tumor-killing potential, which are widely explored in diverse cancer therapies and combined therapies. Reducing the concentration of Cu2+/Cu+ is another cancer-killing method, and chelators can meet this need. More importantly, challenges and future prospects are identified for further research.
{"title":"Recent advances in copper homeostasis-involved tumor theranostics","authors":"Xinghua Ren , Xinyi Luo , Fuchang Wang , Long Wan , Xiaofan Wang , Jinya Xiong , Mengwei Ye , Shiqiao Rui , Zhu Liu , Siling Wang , Qinfu Zhao","doi":"10.1016/j.ajps.2024.100948","DOIUrl":"10.1016/j.ajps.2024.100948","url":null,"abstract":"<div><div>As the third essential trace element in the human body, copper plays a crucial role in various physiological processes, which lays the foundation for its broad applications in cancer treatments. The overview of copper, including pharmacokinetics, signaling pathways, and homeostasis dysregulation, is hereby discussed. Additionally, cuproptosis, as a newly proposed cell death mechanism associated with copper accumulation, is analyzed and further developed for efficient cancer treatment. Different forms of Cu-based nanoparticles and their advantages, as well as limiting factors, are introduced. Moreover, the unique characteristics of Cu-based nanoparticles give rise to their applications in various imaging modalities. In addition, Cu-based nanomaterials are featured by their excellent photothermal property and ROS-associated tumor-killing potential, which are widely explored in diverse cancer therapies and combined therapies. Reducing the concentration of Cu<sup>2+</sup>/Cu<sup>+</sup> is another cancer-killing method, and chelators can meet this need. More importantly, challenges and future prospects are identified for further research.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 5","pages":"Article 100948"},"PeriodicalIF":10.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142444875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.ajps.2024.100950
Xiang Chen , Zhengtao Yong , Yuxuan Xiong , Hai Yang , Chen Xu , Xing Wang , Qingyuan Deng , Jiayuan Li , Xiangliang Yang , Zifu Li
Photodynamic therapy (PDT) can produce high levels of reactive oxygen species (ROS) to kill tumor cells and induce antitumor immunity. However, intracellular antioxidant systems, including glutathione (GSH) system and thioredoxin (Trx) system, limit the accumulation of ROS, resulting in compromised PDT and insufficient immune stimulation. Herein, we designed a nanomedicine PtHPs co-loading photosensitizer pyropheophorbide a (PPa) and cisplatin prodrug Pt–COOH(IV) (Pt (IV)) based on hydroxyethyl starch (HES) to inhibit both GSH and Trx antioxidant systems and achieve potent PDT as well as antitumor immune responses. Specifically, HES-PPa and HES-Pt were obtained by coupling HES with PPa and Pt (IV), and assembled into nanoparticle PtHPs by emulsification method to achieve the purpose of co-delivery of PPa and Pt (IV). PtHPs improved PPa photostability while retaining PPa photodynamic properties. In vitro experiments showed that PtHPs reduced GSH, inhibited Trx system and had better cell-killing effect and ROS generation ability. Subcutaneous tumor models showed that PtHPs had good safety and tumor inhibition effect. Bilateral tumor models suggested that PtHPs promoted the release of damage-associated molecular patterns and the maturation of dendritic cells, induced T cell-mediated immune responses, and thus suppressed the growth of both primary and distal tumors. This study reports a novel platinum-based nanomedicine and provides a new strategy for boosting PDT therapy-mediated antitumor immunity by overcoming intrinsic antioxidant systems.
光动力疗法（PDT）可产生大量活性氧（ROS），从而杀死肿瘤细胞并诱导抗肿瘤免疫。然而，细胞内的抗氧化系统，包括谷胱甘肽（GSH）系统和硫代氧化酶（Trx）系统，限制了ROS的积累，导致光动力疗法受到影响，免疫刺激不足。在此，我们设计了一种基于羟乙基淀粉（HES）的纳米药物PtHPs，其中共载光敏剂吡咯并卟啉a（PPa）和顺铂原药Pt-COOH(IV)（Pt (IV)），以抑制GSH和Trx抗氧化系统，实现强效PDT和抗肿瘤免疫反应。具体来说，将羟乙基淀粉与PPa和Pt（IV）偶联得到HES-PPa和HES-Pt，并通过乳化方法组装成纳米颗粒PtHPs，以达到PPa和Pt（IV）共同递送的目的。实验表明，PtHPs能降低GSH，抑制Trx系统，具有更好的细胞杀伤作用和ROS生成能力。皮下肿瘤模型显示，PtHPs 具有良好的安全性和肿瘤抑制效果。双侧肿瘤模型表明，PtHPs 可促进损伤相关分子模式的释放和树突状细胞的成熟，诱导 T 细胞介导的免疫反应，从而抑制原发性和远端肿瘤的生长。这项研究报告了一种新型铂基纳米药物，并提供了一种通过克服内在抗氧化系统来增强PDT疗法介导的抗肿瘤免疫的新策略。
{"title":"Hydroxyethyl starch conjugates co-assembled nanoparticles promote photodynamic therapy and antitumor immunity by inhibiting antioxidant systems","authors":"Xiang Chen , Zhengtao Yong , Yuxuan Xiong , Hai Yang , Chen Xu , Xing Wang , Qingyuan Deng , Jiayuan Li , Xiangliang Yang , Zifu Li","doi":"10.1016/j.ajps.2024.100950","DOIUrl":"10.1016/j.ajps.2024.100950","url":null,"abstract":"<div><div>Photodynamic therapy (PDT) can produce high levels of reactive oxygen species (ROS) to kill tumor cells and induce antitumor immunity. However, intracellular antioxidant systems, including glutathione (GSH) system and thioredoxin (Trx) system, limit the accumulation of ROS, resulting in compromised PDT and insufficient immune stimulation. Herein, we designed a nanomedicine PtHPs co-loading photosensitizer pyropheophorbide a (PPa) and cisplatin prodrug Pt–COOH(IV) (Pt (IV)) based on hydroxyethyl starch (HES) to inhibit both GSH and Trx antioxidant systems and achieve potent PDT as well as antitumor immune responses. Specifically, HES-PPa and HES-Pt were obtained by coupling HES with PPa and Pt (IV), and assembled into nanoparticle PtHPs by emulsification method to achieve the purpose of co-delivery of PPa and Pt (IV). PtHPs improved PPa photostability while retaining PPa photodynamic properties. <em>In vitro</em> experiments showed that PtHPs reduced GSH, inhibited Trx system and had better cell-killing effect and ROS generation ability. Subcutaneous tumor models showed that PtHPs had good safety and tumor inhibition effect. Bilateral tumor models suggested that PtHPs promoted the release of damage-associated molecular patterns and the maturation of dendritic cells, induced T cell-mediated immune responses, and thus suppressed the growth of both primary and distal tumors. This study reports a novel platinum-based nanomedicine and provides a new strategy for boosting PDT therapy-mediated antitumor immunity by overcoming intrinsic antioxidant systems.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 5","pages":"Article 100950"},"PeriodicalIF":10.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142191723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.ajps.2024.100969
Dan Yan , Yuqian Wang , Weijie Ouyang , Caihong Huang , Qian Chen , Jiaoyue Hu , Zuguo Liu
Retinal neovascularization is a leading cause of blindness. While current anti-VEGF drugs effectively inhibit pathological angiogenesis, some patients develop resistance or reduced responsiveness to treatments over time, leading to diminished effectiveness. In this study, we identified high activation of the cGAS-STING signaling pathway, which exacerbated pathological neovascularization and vessel leakage. We developed an injectable thermo-responsive supramolecular hydrogel loaded with an anti-STING drug. The hydrogel, made of Pluronic F127 (PF·127) consisting of poly(ethylene oxide) and poly(propylene oxide) units, demonstrated excellent transparency and biocompatibility. Importantly, the thermo-sensitive property allowed for precise spatial release of the drug, extending the effective treatment duration of C-176, which suppressed STING activation in the retina, reduced inflammation, and protected retinal tissue. HydroC-176 effectively inhibited microglial cell infiltration and the release of inflammatory angiogenic factors, highlighting its enhanced efficacy. While demonstrating slightly lower effectiveness compared to traditional anti-VEGF therapy, HydroC-176 exhibited more robust capabilities in regulating ocular microenvironmental inflammation. This approach may assist in enhancing the sensitivity and effectiveness of anti-VEGF therapy for reducing ocular inflammation, potentially improving patients’ response to traditional treatment. These results have suggested innovative and comprehensive strategies for the management of retinal neovascularization.
{"title":"Revamping anti-cGAS-STING therapy via an injectable thermo-responsive supramolecular hydrogel for pathological retinal angiogenesis","authors":"Dan Yan , Yuqian Wang , Weijie Ouyang , Caihong Huang , Qian Chen , Jiaoyue Hu , Zuguo Liu","doi":"10.1016/j.ajps.2024.100969","DOIUrl":"10.1016/j.ajps.2024.100969","url":null,"abstract":"<div><div>Retinal neovascularization is a leading cause of blindness. While current anti-VEGF drugs effectively inhibit pathological angiogenesis, some patients develop resistance or reduced responsiveness to treatments over time, leading to diminished effectiveness. In this study, we identified high activation of the cGAS-STING signaling pathway, which exacerbated pathological neovascularization and vessel leakage. We developed an injectable thermo-responsive supramolecular hydrogel loaded with an anti-STING drug. The hydrogel, made of Pluronic F127 (PF·127) consisting of poly(ethylene oxide) and poly(propylene oxide) units, demonstrated excellent transparency and biocompatibility. Importantly, the thermo-sensitive property allowed for precise spatial release of the drug, extending the effective treatment duration of C-176, which suppressed STING activation in the retina, reduced inflammation, and protected retinal tissue. Hydro<sup>C-176</sup> effectively inhibited microglial cell infiltration and the release of inflammatory angiogenic factors, highlighting its enhanced efficacy. While demonstrating slightly lower effectiveness compared to traditional anti-VEGF therapy, Hydro<sup>C-176</sup> exhibited more robust capabilities in regulating ocular microenvironmental inflammation. This approach may assist in enhancing the sensitivity and effectiveness of anti-VEGF therapy for reducing ocular inflammation, potentially improving patients’ response to traditional treatment. These results have suggested innovative and comprehensive strategies for the management of retinal neovascularization.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 5","pages":"Article 100969"},"PeriodicalIF":10.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142444740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.ajps.2024.100947
Simin Lee , Jun Young Park , Hye Kyoung Hong , Joo Young Son , Byungwook Kim , Jae Yong Chung , Se Joon Woo , Ki Dong Park
Retinal vascular disease is the leading cause of visual impairment. Although intravitreal drug injections are the most suitable approach for addressing retinal disorders, existing clinical treatments necessitate repeated administration, imposing a substantial burden on patients with various intraocular complications. This study introduces an injectable and biodegradable hyaluronan microgel (Hm)-embedded gelatin–poly(ethylene glycol)–tyramine hydrogel (HmGh) designed for sustained intravitreal ranibizumab (RBZ) delivery to reduce patient burden and minimize the side effects associated with frequent injections. Hm exhibited a controlled RBZ loading capacity and release profile. HmGh effectively controlled the initial burst release and overall release profile. Cytocompatibility and cellular drug efficacy were also demonstrated. In an animal study, HmGh maintained RBZ concentrations in the vitreous and retina for >120 d. Pharmacokinetic studies showed that the half-life of RBZ-loaded HmGh in the vitreous and retina was 2.55 and 2.05 times longer than that of RBZ-loaded Hm, respectively, and 9.58 and 38.46 times longer than that of RBZ solution, respectively. Importantly, the initial RBZ elimination from HmGh to the aqueous humor was significantly reduced compared to that from the Hm and RBZ solutions. Intraocular degradation and safety were comprehensively evaluated using fundus imaging and histological analyses. In conclusion, this injectable microgel-embedded hydrogel formulation is a promising prolonged drug delivery system for treating various posterior segment eye diseases.
{"title":"Intravitreal long-term sustained ranibizumab delivery using injectable microgel-embedded hydrogel","authors":"Simin Lee , Jun Young Park , Hye Kyoung Hong , Joo Young Son , Byungwook Kim , Jae Yong Chung , Se Joon Woo , Ki Dong Park","doi":"10.1016/j.ajps.2024.100947","DOIUrl":"10.1016/j.ajps.2024.100947","url":null,"abstract":"<div><div>Retinal vascular disease is the leading cause of visual impairment. Although intravitreal drug injections are the most suitable approach for addressing retinal disorders, existing clinical treatments necessitate repeated administration, imposing a substantial burden on patients with various intraocular complications. This study introduces an injectable and biodegradable hyaluronan microgel (Hm)-embedded gelatin–poly(ethylene glycol)–tyramine hydrogel (HmGh) designed for sustained intravitreal ranibizumab (RBZ) delivery to reduce patient burden and minimize the side effects associated with frequent injections. Hm exhibited a controlled RBZ loading capacity and release profile. HmGh effectively controlled the initial burst release and overall release profile. Cytocompatibility and cellular drug efficacy were also demonstrated. In an animal study, HmGh maintained RBZ concentrations in the vitreous and retina for >120 d. Pharmacokinetic studies showed that the half-life of RBZ-loaded HmGh in the vitreous and retina was 2.55 and 2.05 times longer than that of RBZ-loaded Hm, respectively, and 9.58 and 38.46 times longer than that of RBZ solution, respectively. Importantly, the initial RBZ elimination from HmGh to the aqueous humor was significantly reduced compared to that from the Hm and RBZ solutions. Intraocular degradation and safety were comprehensively evaluated using fundus imaging and histological analyses. In conclusion, this injectable microgel-embedded hydrogel formulation is a promising prolonged drug delivery system for treating various posterior segment eye diseases.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 5","pages":"Article 100947"},"PeriodicalIF":10.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142191744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.ajps.2024.100945
Taozhao Yu , Irene Shuping Zhao , Hongguang Pan , Jianhua Yang , Huanan Wang , Yongqiang Deng , Yang Zhang
The clinical need for effective bone regeneration in compromised conditions continues to drive demand for innovative solutions. Among emerging strategies, extracellular vesicles (EVs) have shown promise as an acellular approach for bone regeneration. However, their efficacy is hindered by rapid sequestration and clearance when administered via bolus injection. To address this challenge, EV-functionalized scaffolds have recently been proposed as an alternative delivery strategy to enhance EV retention and subsequent healing efficacy. This review aims to consolidate recent advancements in the development of EV-functionalized scaffolds for augmenting bone regeneration. It explores various sources of EVs and different strategies for integrating them into biomaterials. Furthermore, the mechanisms underlying their therapeutic effects in bone regeneration are elucidated. Current limitations in clinical translation and perspectives on the design of more efficient EVs for improved therapeutic efficacy are also presented. Overall, this review can provide inspiration for the development of novel EV-assisted grafts with superior bone regeneration potential.
在受损条件下进行有效骨再生的临床需求不断推动着对创新解决方案的需求。在新出现的策略中，细胞外囊泡（EVs）作为一种细胞外骨再生方法已显示出前景。然而，通过栓剂注射给药时，细胞外囊泡会迅速被螯合和清除，从而影响其功效。为了应对这一挑战，最近有人提出了 EV 功能化支架作为替代给药策略，以提高 EV 的保留率和随后的愈合效果。本综述旨在总结最近在开发用于促进骨再生的 EV 功能化支架方面取得的进展。文章探讨了 EVs 的各种来源以及将 EVs 整合到生物材料中的不同策略。此外，还阐明了它们在骨再生中的治疗作用机制。此外，还介绍了目前临床应用的局限性，以及设计更有效的 EVs 以提高疗效的前景。总之，本综述可为开发具有卓越骨再生潜力的新型 EV 辅助移植物提供灵感。
{"title":"Extracellular vesicle-functionalized bioactive scaffolds for bone regeneration","authors":"Taozhao Yu , Irene Shuping Zhao , Hongguang Pan , Jianhua Yang , Huanan Wang , Yongqiang Deng , Yang Zhang","doi":"10.1016/j.ajps.2024.100945","DOIUrl":"10.1016/j.ajps.2024.100945","url":null,"abstract":"<div><div>The clinical need for effective bone regeneration in compromised conditions continues to drive demand for innovative solutions. Among emerging strategies, extracellular vesicles (EVs) have shown promise as an acellular approach for bone regeneration. However, their efficacy is hindered by rapid sequestration and clearance when administered via bolus injection. To address this challenge, EV-functionalized scaffolds have recently been proposed as an alternative delivery strategy to enhance EV retention and subsequent healing efficacy. This review aims to consolidate recent advancements in the development of EV-functionalized scaffolds for augmenting bone regeneration. It explores various sources of EVs and different strategies for integrating them into biomaterials. Furthermore, the mechanisms underlying their therapeutic effects in bone regeneration are elucidated. Current limitations in clinical translation and perspectives on the design of more efficient EVs for improved therapeutic efficacy are also presented. Overall, this review can provide inspiration for the development of novel EV-assisted grafts with superior bone regeneration potential.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 5","pages":"Article 100945"},"PeriodicalIF":10.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141695052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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