Pub Date : 2025-02-01Epub Date: 2025-01-04DOI: 10.1016/j.ajps.2025.101015
Jiayuan Zhang , Xinyu Yang , Zhichao Chang , Wenwei Zhu , Yuhua Ma , Haisheng He
The recent commercialization of gene products has sparked significant interest in gene therapy, necessitating efficient and precise gene delivery via various vectors. Currently, viral vectors and lipid-based nanocarriers are the predominant choices and have been extensively investigated and reviewed. Beyond these vectors, polymeric nanocarriers also hold the promise in therapeutic gene delivery owing to their versatile functionalities, such as improving the stability, cellar uptake and endosomal escape of nucleic acid drugs, along with precise delivery to targeted tissues. This review presents a brief overview of the status quo of the emerging polymeric nanocarriers for therapeutic gene delivery, focusing on key cationic polymers, nanocarrier types, and preparation methods. It also highlights targeted diseases, strategies to improve delivery efficiency, and potential future directions in this research area. The review is hoped to inspire the development, optimization, and clinical translation of highly efficient polymeric nanocarriers for therapeutic gene delivery.
{"title":"Polymeric nanocarriers for therapeutic gene delivery","authors":"Jiayuan Zhang , Xinyu Yang , Zhichao Chang , Wenwei Zhu , Yuhua Ma , Haisheng He","doi":"10.1016/j.ajps.2025.101015","DOIUrl":"10.1016/j.ajps.2025.101015","url":null,"abstract":"<div><div>The recent commercialization of gene products has sparked significant interest in gene therapy, necessitating efficient and precise gene delivery via various vectors. Currently, viral vectors and lipid-based nanocarriers are the predominant choices and have been extensively investigated and reviewed. Beyond these vectors, polymeric nanocarriers also hold the promise in therapeutic gene delivery owing to their versatile functionalities, such as improving the stability, cellar uptake and endosomal escape of nucleic acid drugs, along with precise delivery to targeted tissues. This review presents a brief overview of the status quo of the emerging polymeric nanocarriers for therapeutic gene delivery, focusing on key cationic polymers, nanocarrier types, and preparation methods. It also highlights targeted diseases, strategies to improve delivery efficiency, and potential future directions in this research area. The review is hoped to inspire the development, optimization, and clinical translation of highly efficient polymeric nanocarriers for therapeutic gene delivery.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 1","pages":"Article 101015"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143102269","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 : 2025-02-01Epub Date: 2024-12-16DOI: 10.1016/j.ajps.2024.101009
Hai V. Ngo , Hy D. Nguyen , Beom-Jin Lee
A structural conjugate (HOC) of polysaccharide, hyaluronic acid (HA) with different ratios of oleic acid (OA) via cystamine (CYS) linker as a new ocular biomaterial was developed. The HOCs with controlled degrees of substitution of OA (4.6 %, 8.3 % and 12.2 %) were synthesized to form self-assembled HA-CYS-OA nanoparticles (HONs, HON1, HON2, HON3). A poorly water-soluble cyclosporine A (CsA) to be used for the treatment of multifactorial dry eye disease (DED) was chosen as model drug. CsA-loaded HONs exhibited improved solution transparency via solubilizing capacity of HON, and increased in vitro drug permeation compared to Restasis®. The physicochemical properties of CsA-loaded HONs such as nano behaviors, solution transparency, drug release, drug permeation and ocular cytocompatibility were highly variable according to the ratios of OA substitution. Interestingly, this CsA-loaded HON1 as optimal ocular nanoformulation showed markedly augmented macrophage polarization into the M2 phenotype, downregulated the expression of proinflammatory cytokines levels in LPS-induced M1 macrophage, and effectively inhibited VEGF-induced endothelial cell proliferation and capillary-like tube formation by the synergistic effect of CsA and HON1 containing OA at the same time. Collectively, the current fatty acid conjugated to HA, named fattigation platform, providing the roles and physicochemical properties via structural features of HA could be a promising co-delivery strategy of drug and fatty acid for DED and other ophthalmic disease treatments.
{"title":"Hyaluronic acid conjugates with controlled oleic acid substitution as new nanomaterials for improving ocular co-delivery of cyclosporine A and oleic acid","authors":"Hai V. Ngo , Hy D. Nguyen , Beom-Jin Lee","doi":"10.1016/j.ajps.2024.101009","DOIUrl":"10.1016/j.ajps.2024.101009","url":null,"abstract":"<div><div>A structural conjugate (HOC) of polysaccharide, hyaluronic acid (HA) with different ratios of oleic acid (OA) via cystamine (CYS) linker as a new ocular biomaterial was developed. The HOCs with controlled degrees of substitution of OA (4.6 %, 8.3 % and 12.2 %) were synthesized to form self-assembled HA-CYS-OA nanoparticles (HONs, HON1, HON2, HON3). A poorly water-soluble cyclosporine A (CsA) to be used for the treatment of multifactorial dry eye disease (DED) was chosen as model drug. CsA-loaded HONs exhibited improved solution transparency via solubilizing capacity of HON, and increased <em>in vitro</em> drug permeation compared to Restasis®. The physicochemical properties of CsA-loaded HONs such as nano behaviors, solution transparency, drug release, drug permeation and ocular cytocompatibility were highly variable according to the ratios of OA substitution. Interestingly, this CsA-loaded HON1 as optimal ocular nanoformulation showed markedly augmented macrophage polarization into the M2 phenotype, downregulated the expression of proinflammatory cytokines levels in LPS-induced M1 macrophage, and effectively inhibited VEGF-induced endothelial cell proliferation and capillary-like tube formation by the synergistic effect of CsA and HON1 containing OA at the same time. Collectively, the current fatty acid conjugated to HA, named fattigation platform, providing the roles and physicochemical properties via structural features of HA could be a promising co-delivery strategy of drug and fatty acid for DED and other ophthalmic disease treatments.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 1","pages":"Article 101009"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143102270","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 : 2025-02-01Epub Date: 2025-01-10DOI: 10.1016/j.ajps.2025.101017
Yuhan Wang , Yixin Tang , Lei Guo , Xi Yang , Shanli Wu , Ying Yue , Caina Xu
Biological nanotechnologies based on functional nanoplatforms have synergistically catalyzed the emergence of cancer therapies. As a subtype of metal-organic frameworks (MOFs), zeolitic imidazolate frameworks (ZIFs) have exploded in popularity in the field of biomaterials as excellent protective materials with the advantages of conformational flexibility, thermal and chemical stability, and functional controllability. With these superior properties, the applications of ZIF-based materials in combination with various therapies for cancer treatment have grown rapidly in recent years, showing remarkable achievements and great potential. This review elucidates the recent advancements in the use of ZIFs as drug delivery agents for cancer therapy. The structures, synthesis methods, properties, and various modifiers of ZIFs used in oncotherapy are presented. Recent advances in the application of ZIF-based nanoparticles as single or combination tumor treatments are reviewed. Furthermore, the future prospects, potential limitations, and challenges of the application of ZIF-based nanomaterials in cancer treatment are discussed. We except to fully explore the potential of ZIF-based materials to present a clear outline for their application as an effective cancer treatment to help them achieve early clinical application.
{"title":"Recent advances in zeolitic imidazolate frameworks as drug delivery systems for cancer therapy","authors":"Yuhan Wang , Yixin Tang , Lei Guo , Xi Yang , Shanli Wu , Ying Yue , Caina Xu","doi":"10.1016/j.ajps.2025.101017","DOIUrl":"10.1016/j.ajps.2025.101017","url":null,"abstract":"<div><div>Biological nanotechnologies based on functional nanoplatforms have synergistically catalyzed the emergence of cancer therapies. As a subtype of metal-organic frameworks (MOFs), zeolitic imidazolate frameworks (ZIFs) have exploded in popularity in the field of biomaterials as excellent protective materials with the advantages of conformational flexibility, thermal and chemical stability, and functional controllability. With these superior properties, the applications of ZIF-based materials in combination with various therapies for cancer treatment have grown rapidly in recent years, showing remarkable achievements and great potential. This review elucidates the recent advancements in the use of ZIFs as drug delivery agents for cancer therapy. The structures, synthesis methods, properties, and various modifiers of ZIFs used in oncotherapy are presented. Recent advances in the application of ZIF-based nanoparticles as single or combination tumor treatments are reviewed. Furthermore, the future prospects, potential limitations, and challenges of the application of ZIF-based nanomaterials in cancer treatment are discussed. We except to fully explore the potential of ZIF-based materials to present a clear outline for their application as an effective cancer treatment to help them achieve early clinical application.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 1","pages":"Article 101017"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143102274","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 : 2025-02-01Epub Date: 2024-12-12DOI: 10.1016/j.ajps.2024.101006
Youngki Lee , Subin Kang , Le Thi Thuy , Mincheol Son , Jae Young Park , Sung Bin Ahn , Minji Kang , Jihun Oh , Joon Sig Choi , Minhyung Lee
Herpes simplex virus thymidine kinase (HSVtk) gene therapy is a promising strategy for glioblastoma therapy. However, delivery of plasmid DNA (pDNA) encoding HSVtk into the brain by systemic administration is a challenge since pDNA can hardly penetrate the blood-brain barrier. In this study, an exosome-membrane (EM) and polymer-based hybrid complex was developed for systemic delivery of pDNA into the brain. Histidine/arginine-linked polyamidoamine (PHR) was used as a carrier. PHR binds to pDNA by electrostatic interaction. The pDNA/PHR complex was mixed with EM and subjected to extrusion to produce pDNA/PHR-EM hybrid complex. For glioblastoma targeting, T7 peptide was attached to the pDNA/PHR-EM complex. Both pDNA/PHR-EM and T7-decorated pDNA/PHR-EM (pDNA/PHR-EM-T7) had a surface charge of –5 mV and a size of 280 nm. Transfection assays indicated that pDNA/PHR-EM-T7 enhanced the transfection to C6 cells compared with pDNA/PHR-EM. Intravenous administration of pHSVtk/PHR-EM-T7 showed that pHSVtk/PHR-EM and pHSVtk/PHR-EM-T7 delivered pHSVtk more efficiently than pHSVtk/lipofectamine and pHSVtk/PHR into glioblastoma in vivo. pHSVtk/PHR-EM-T7 had higher delivery efficiency than pHSVtk/PHR-EM. As a result, the HSVtk expression and apoptosis levels in the tumors of the pHSVtk/PHR-EM-T7 group were higher than those of the other control groups. Therefore, the pDNA/PHR-EM-T7 hybrid complex is a useful carrier for systemic delivery of pHSVtk to glioblastoma.
单纯疱疹病毒胸苷激酶（HSVtk）基因治疗是一种很有前途的胶质母细胞瘤治疗策略。然而，编码HSVtk的质粒DNA （pDNA）通过全身给药进入大脑是一个挑战，因为pDNA很难穿透血脑屏障。在这项研究中，开发了一种外泌体-膜（EM）和基于聚合物的杂交复合物，用于将pDNA全身递送到大脑中。以组氨酸/精氨酸连接聚酰胺胺（PHR）为载体。PHR通过静电相互作用与pDNA结合。将pDNA/PHR配合物与EM混合，挤压得到pDNA/PHR-EM杂化配合物。针对胶质母细胞瘤，T7肽被附着在pDNA/ phrr - em复合物上。pDNA/PHR-EM和t7修饰的pDNA/PHR-EM （pDNA/PHR-EM- t7）表面电荷均为-5 mV，尺寸为280 nm。转染实验表明，与pDNA/PHR-EM相比，pDNA/PHR-EM- t7对C6细胞的转染增强。静脉给药pHSVtk/PHR- em - t7显示pHSVtk/PHR- em和pHSVtk/PHR- em - t7在体内比pHSVtk/脂质体和pHSVtk/PHR更有效地将pHSVtk输送到胶质母细胞瘤中。pHSVtk/PHR-EM- t7的输送效率高于pHSVtk/PHR-EM。结果显示，pHSVtk/ phrr - em - t7组肿瘤中HSVtk的表达和凋亡水平均高于其他对照组。因此，pDNA/ phrr - em - t7杂交复合体是将pHSVtk系统递送至胶质母细胞瘤的有用载体。
{"title":"Exosome-membrane and polymer-based hybrid-complex for systemic delivery of plasmid DNA into brains for the treatment of glioblastoma","authors":"Youngki Lee , Subin Kang , Le Thi Thuy , Mincheol Son , Jae Young Park , Sung Bin Ahn , Minji Kang , Jihun Oh , Joon Sig Choi , Minhyung Lee","doi":"10.1016/j.ajps.2024.101006","DOIUrl":"10.1016/j.ajps.2024.101006","url":null,"abstract":"<div><div>Herpes simplex virus thymidine kinase (HSVtk) gene therapy is a promising strategy for glioblastoma therapy. However, delivery of plasmid DNA (pDNA) encoding HSVtk into the brain by systemic administration is a challenge since pDNA can hardly penetrate the blood-brain barrier. In this study, an exosome-membrane (EM) and polymer-based hybrid complex was developed for systemic delivery of pDNA into the brain. Histidine/arginine-linked polyamidoamine (PHR) was used as a carrier. PHR binds to pDNA by electrostatic interaction. The pDNA/PHR complex was mixed with EM and subjected to extrusion to produce pDNA/PHR-EM hybrid complex. For glioblastoma targeting, T7 peptide was attached to the pDNA/PHR-EM complex. Both pDNA/PHR-EM and T7-decorated pDNA/PHR-EM (pDNA/PHR-EM-T7) had a surface charge of –5 mV and a size of 280 nm. Transfection assays indicated that pDNA/PHR-EM-T7 enhanced the transfection to C6 cells compared with pDNA/PHR-EM. Intravenous administration of pHSVtk/PHR-EM-T7 showed that pHSVtk/PHR-EM and pHSVtk/PHR-EM-T7 delivered pHSVtk more efficiently than pHSVtk/lipofectamine and pHSVtk/PHR into glioblastoma <em>in vivo</em>. pHSVtk/PHR-EM-T7 had higher delivery efficiency than pHSVtk/PHR-EM. As a result, the HSVtk expression and apoptosis levels in the tumors of the pHSVtk/PHR-EM-T7 group were higher than those of the other control groups. Therefore, the pDNA/PHR-EM-T7 hybrid complex is a useful carrier for systemic delivery of pHSVtk to glioblastoma.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 1","pages":"Article 101006"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143102273","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}
In clinical settings, regenerating critical-sized calvarial bone defects presents substantial problems owing to the intricacy of surgical methods, restricted bone growth medications, and a scarcity of commercial bone grafts. To treat this life-threatening issue, improved biofunctional grafts capable of properly healing critical-sized bone defects are required. In this study, we effectively created anti-fracture hydrogel systems using spongy-like metal-organic (magnesium-phosphate) coordinated chitosan-modified injectable hydrogels (CPMg) loaded with a bioinspired neobavaisoflavone (NBF) component. The CPMg-NBF hydrogels showed outstanding anti-fracture capabilities during compression testing and retained exceptional mechanical stability even after 28 d of immersion in phosphate-buffered saline. They also demonstrated prolonged and stable release profiles of Mg2+ and NBF. Importantly, CPMg-NBF hydrogels revealed robust biphasic mineralization and were non-toxic to MC3T3-E1 cells. To better understand the underlying mechanism of Mg2+ and NBF component, as well as their synergistic effect on osteogenesis, we investigated the expression of key osteogenic proteins in the p38 MAPK and NOTCH pathways. Our results showed that CPMg-NBF hydrogels greatly increased the expression of osteogenic proteins (Runx2, OCN, OPN, BMPS and ALP). In vivo experiments showed that the implantation of CPMg-NBF hydrogels resulted in a significant increase in new bone growth within critical-sized calvarial defects. Based on these findings, we expect that the CPMg-NBF supramolecular hydrogel has tremendous promise for use as a therapeutic biomaterial for treating critical-sized calvarial defects.
{"title":"Biofunctional supramolecular injectable hydrogel with spongy-like metal-organic coordination for effective repair of critical-sized calvarial defects","authors":"Yingqi Chen , Zuocheng Qiu , Xueling Hu , Tiehua Wang , Guoqing Li , Ziling Tang , Chongzhou Fang , Weibei Sheng , Jin Zhao , Fei Yu , Jian Weng , Anjaneyulu Udduttula , Geetha Manivasagam , Hui Zeng","doi":"10.1016/j.ajps.2024.100988","DOIUrl":"10.1016/j.ajps.2024.100988","url":null,"abstract":"<div><div>In clinical settings, regenerating critical-sized calvarial bone defects presents substantial problems owing to the intricacy of surgical methods, restricted bone growth medications, and a scarcity of commercial bone grafts. To treat this life-threatening issue, improved biofunctional grafts capable of properly healing critical-sized bone defects are required. In this study, we effectively created anti-fracture hydrogel systems using spongy-like metal-organic (magnesium-phosphate) coordinated chitosan-modified injectable hydrogels (CPMg) loaded with a bioinspired neobavaisoflavone (NBF) component. The CPMg-NBF hydrogels showed outstanding anti-fracture capabilities during compression testing and retained exceptional mechanical stability even after 28 d of immersion in phosphate-buffered saline. They also demonstrated prolonged and stable release profiles of Mg<sup>2+</sup> and NBF. Importantly, CPMg-NBF hydrogels revealed robust biphasic mineralization and were non-toxic to MC3T3-E1 cells. To better understand the underlying mechanism of Mg<sup>2+</sup> and NBF component, as well as their synergistic effect on osteogenesis, we investigated the expression of key osteogenic proteins in the p38 MAPK and NOTCH pathways. Our results showed that CPMg-NBF hydrogels greatly increased the expression of osteogenic proteins (Runx2, OCN, OPN, BMPS and ALP). <em>In vivo</em> experiments showed that the implantation of CPMg-NBF hydrogels resulted in a significant increase in new bone growth within critical-sized calvarial defects. Based on these findings, we expect that the CPMg-NBF supramolecular hydrogel has tremendous promise for use as a therapeutic biomaterial for treating critical-sized calvarial defects.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 1","pages":"Article 100988"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143102272","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 : 2025-02-01Epub Date: 2025-01-02DOI: 10.1016/j.ajps.2024.101014
Kyeng Min Park
A new type of amphiphiles bearing macrocycle such as cucurbit[7]uril (CB[7]) spontaneously forms a nanomaterial in water, specifically vesicles (tACB[7] vesicles) with a positive surface charge, verified through various analytical techniques including TIRF, DLS and TEM. Functional validation not only reveals the accessibility of the CB[7] portal on these vesicles allowing CB[7]-based host-guest interactions with various functional guest molecules such as fluorescein isothiocyanate conjugated adamantylammonium and spermine (FITC-AdA and FITC-SPM, respectively) using confocal laser scanning microscopy, but also showcases the effective internalization of tACB[7] vesicles into cancer cells with the anticancer drug oxaliplatin (OxPt), as a guest to CB[7], through in vitro cell experiments. Hence, this study provides a blueprint to impart amphiphilic properties to CB[7] through synthetic design and highlights the potential of CB[7] derivatives as a new class of unconventional amphiphiles self-assembling into functional nanomaterials for advanced drug delivery.
{"title":"Efficient anticancer drug delivery using nano-colloids self-assembled with an unconventional amphiphile bearing pumpkin-shaped host molecule","authors":"Kyeng Min Park","doi":"10.1016/j.ajps.2024.101014","DOIUrl":"10.1016/j.ajps.2024.101014","url":null,"abstract":"<div><div>A new type of amphiphiles bearing macrocycle such as cucurbit[7]uril (CB[7]) spontaneously forms a nanomaterial in water, specifically vesicles (<em>t</em>ACB[7] vesicles) with a positive surface charge, verified through various analytical techniques including TIRF, DLS and TEM. Functional validation not only reveals the accessibility of the CB[7] portal on these vesicles allowing CB[7]-based host-guest interactions with various functional guest molecules such as fluorescein isothiocyanate conjugated adamantylammonium and spermine (FITC-AdA and FITC-SPM, respectively) using confocal laser scanning microscopy, but also showcases the effective internalization of <em>t</em>ACB[7] vesicles into cancer cells with the anticancer drug oxaliplatin (OxPt), as a guest to CB[7], through <em>in vitro</em> cell experiments. Hence, this study provides a blueprint to impart amphiphilic properties to CB[7] through synthetic design and highlights the potential of CB[7] derivatives as a new class of unconventional amphiphiles self-assembling into functional nanomaterials for advanced drug delivery.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 1","pages":"Article 101014"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143102213","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 : 2025-02-01Epub Date: 2024-11-02DOI: 10.1016/j.ajps.2024.100990
Mengying Cheng , Tianxiang Yue , Hong Wang , Lai Jiang , Qiaoling Huang , Fanzhu Li
Atherosclerosis (AS) is a progressive inflammatory disease, and thrombosis most likely leads to cardiovascular morbidity and mortality globally. Thrombolytic drugs alone cannot completely prevent thrombotic events, and treatments targeting thrombosis also need to regulate the inflammatory process. Based on the dynamic pathological development of AS, biomimetic thrombus-targeted nanoparticles HMTL@PM were prepared. Hirudin and lumbrukinase, effective substances of traditional Chinese medicine, were self-assembled under the action of tannic acid and Mn2+. HMTL@PM dissociated in the weakly acidic microenvironment of atherosclerosis and exhibited excellent therapeutic effects, including alleviating inflammation, dissolving thrombus, anticoagulation, and promoting cholesterol efflux. HMTL@PM effectively regulated the progression of AS and provided a new perspective for the development of drug delivery systems for AS therapy, which holds important research significance for reducing the mortality of cardiovascular and cerebrovascular diseases.
{"title":"Biomimetic nanoparticles co-deliver hirudin and lumbrukinase to ameliorate thrombus and inflammation for atherosclerosis therapy","authors":"Mengying Cheng , Tianxiang Yue , Hong Wang , Lai Jiang , Qiaoling Huang , Fanzhu Li","doi":"10.1016/j.ajps.2024.100990","DOIUrl":"10.1016/j.ajps.2024.100990","url":null,"abstract":"<div><div>Atherosclerosis (AS) is a progressive inflammatory disease, and thrombosis most likely leads to cardiovascular morbidity and mortality globally. Thrombolytic drugs alone cannot completely prevent thrombotic events, and treatments targeting thrombosis also need to regulate the inflammatory process. Based on the dynamic pathological development of AS, biomimetic thrombus-targeted nanoparticles HMTL@PM were prepared. Hirudin and lumbrukinase, effective substances of traditional Chinese medicine, were self-assembled under the action of tannic acid and Mn<sup>2+</sup>. HMTL@PM dissociated in the weakly acidic microenvironment of atherosclerosis and exhibited excellent therapeutic effects, including alleviating inflammation, dissolving thrombus, anticoagulation, and promoting cholesterol efflux. HMTL@PM effectively regulated the progression of AS and provided a new perspective for the development of drug delivery systems for AS therapy, which holds important research significance for reducing the mortality of cardiovascular and cerebrovascular diseases.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 1","pages":"Article 100990"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143102276","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 : 2025-02-01Epub Date: 2024-11-12DOI: 10.1016/j.ajps.2024.100993
Fugen Wu , Xingsi An , Shize Li , Chenyu Qiu , Yixuan Zhu , Zhanzheng Ye , Shengnan Song , Yunzhi Wang , Dingchao Shen , Xinyu Di , Yinsha Yao , Wanling Zhu , Xinyu Jiang , Xianbao Shi , Ruijie Chen , Longfa Kou
Chemoimmunotherapy has the potential to enhance chemotherapy and modulate the immunosuppressive tumor microenvironment by activating immunogenic cell death (ICD), making it a promising strategy for clinical application. Alantolactone (A) was found to augment the anticancer efficacy of paclitaxel (P) at a molar ratio of 1:0.5 (P:A) through induction of more potent ICD via modulation of STAT3 signaling pathways. Nano drug delivery systems can synergistically combine natural drugs with conventional chemotherapeutic agents, thereby enhancing multi-drug chemoimmunotherapy. To improve tumor targeting ability and bioavailability of hydrophobic drugs, an amphiphilic prodrug conjugate (HA-PTX) was chemically modified with paclitaxel (PTX) and hyaluronic acid (HA) as a backbone. Based on this concept, CD44-targeted nanodrugs (A@HAP NPs) were developed for co-delivery of A and P in colorectal cancer treatment, aiming to achieve synergistic toxicity-based chemo-immunotherapy. The uniform size and high drug loading capacity of A@HAP NPs facilitated their accumulation within tumors through enhanced permeability and retention effect as well as HA-mediated targeting, providing a solid foundation for subsequent synergistic therapy and immunoregulation. In vitro and in vivo studies demonstrated that A@HAP NPs exhibited potent cytotoxicity against tumor cells while also remodeling the immune-suppressive tumor microenvironment by promoting antigen presentation and inducing dendritic cell maturation, thus offering a novel approach for colorectal cancer chemoimmunotherapy.
{"title":"Enhancing chemoimmunotherapy for colorectal cancer with paclitaxel and alantolactone via CD44-Targeted nanoparticles: A STAT3 signaling pathway modulation approach","authors":"Fugen Wu , Xingsi An , Shize Li , Chenyu Qiu , Yixuan Zhu , Zhanzheng Ye , Shengnan Song , Yunzhi Wang , Dingchao Shen , Xinyu Di , Yinsha Yao , Wanling Zhu , Xinyu Jiang , Xianbao Shi , Ruijie Chen , Longfa Kou","doi":"10.1016/j.ajps.2024.100993","DOIUrl":"10.1016/j.ajps.2024.100993","url":null,"abstract":"<div><div>Chemoimmunotherapy has the potential to enhance chemotherapy and modulate the immunosuppressive tumor microenvironment by activating immunogenic cell death (ICD), making it a promising strategy for clinical application. Alantolactone (A) was found to augment the anticancer efficacy of paclitaxel (P) at a molar ratio of 1:0.5 (P:A) through induction of more potent ICD via modulation of STAT3 signaling pathways. Nano drug delivery systems can synergistically combine natural drugs with conventional chemotherapeutic agents, thereby enhancing multi-drug chemoimmunotherapy. To improve tumor targeting ability and bioavailability of hydrophobic drugs, an amphiphilic prodrug conjugate (HA-PTX) was chemically modified with paclitaxel (PTX) and hyaluronic acid (HA) as a backbone. Based on this concept, CD44-targeted nanodrugs (A@HAP NPs) were developed for co-delivery of A and P in colorectal cancer treatment, aiming to achieve synergistic toxicity-based chemo-immunotherapy. The uniform size and high drug loading capacity of A@HAP NPs facilitated their accumulation within tumors through enhanced permeability and retention effect as well as HA-mediated targeting, providing a solid foundation for subsequent synergistic therapy and immunoregulation. <em>In vitro</em> and <em>in vivo</em> studies demonstrated that A@HAP NPs exhibited potent cytotoxicity against tumor cells while also remodeling the immune-suppressive tumor microenvironment by promoting antigen presentation and inducing dendritic cell maturation, thus offering a novel approach for colorectal cancer chemoimmunotherapy.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 1","pages":"Article 100993"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143102275","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}
Arthritis is an inflammatory joint disorder that progressively impairs function and diminishes quality of life. Conventional therapies often prove ineffective, as oral administration lacks specificity, resulting in off-target side effects like hepatotoxicity and GIT-related issues. Intravenous administration causes systemic side effects. The characteristic joint-localized symptoms such as pain, stiffness, and inflammation make the localized drug delivery suitable for managing arthritis. Topical/transdermal/intra-articular routes have become viable options for drug delivery in treating arthritis. However, challenges with those localized drug delivery routes include skin barrier and cartilage impermeability. Additionally, conventional intra-articular drug delivery also leads to rapid clearance of drugs from the synovial joint tissue. To circumvent these limitations, researchers have developed nanocarriers that enhance drug permeability through skin and cartilage, influencing localized action. Gel-based nanoengineered therapy employs a gel matrix to incorporate the drug-encapsulated nanocarriers. This approach combines the benefits of gels and nanocarriers to enhance therapeutic effects and improve patient compliance. This review emphasizes deep insights into drug delivery using diverse gel-based novel nanocarriers, exploring their various applications embedded in hyaluronic acid (biopolymer)–based gels, carbopol-based gels, and others. Furthermore, this review discusses the influence of nanocarrier pharmacokinetics on the localization and therapeutic manipulation of macrophages mediated by nanocarriers. The ELVIS (extravasation through leaky vasculature and inflammatory cell-mediated sequestration) effect associated with arthritis is advantageous in drug delivery. Simply put, the ELVIS effect refers to the extravasation of nanocarriers through leaky vasculatures, which finally results in the accumulation of nanocarriers in the joint cavity.
{"title":"Deep-insights: Nanoengineered gel-based localized drug delivery for arthritis management","authors":"Anitha Sriram , Harshada Ithape , Pankaj Kumar Singh","doi":"10.1016/j.ajps.2024.101012","DOIUrl":"10.1016/j.ajps.2024.101012","url":null,"abstract":"<div><div>Arthritis is an inflammatory joint disorder that progressively impairs function and diminishes quality of life. Conventional therapies often prove ineffective, as oral administration lacks specificity, resulting in off-target side effects like hepatotoxicity and GIT-related issues. Intravenous administration causes systemic side effects. The characteristic joint-localized symptoms such as pain, stiffness, and inflammation make the localized drug delivery suitable for managing arthritis. Topical/transdermal/intra-articular routes have become viable options for drug delivery in treating arthritis. However, challenges with those localized drug delivery routes include skin barrier and cartilage impermeability. Additionally, conventional intra-articular drug delivery also leads to rapid clearance of drugs from the synovial joint tissue. To circumvent these limitations, researchers have developed nanocarriers that enhance drug permeability through skin and cartilage, influencing localized action. Gel-based nanoengineered therapy employs a gel matrix to incorporate the drug-encapsulated nanocarriers. This approach combines the benefits of gels and nanocarriers to enhance therapeutic effects and improve patient compliance. This review emphasizes deep insights into drug delivery using diverse gel-based novel nanocarriers, exploring their various applications embedded in hyaluronic acid (biopolymer)–based gels, carbopol-based gels, and others. Furthermore, this review discusses the influence of nanocarrier pharmacokinetics on the localization and therapeutic manipulation of macrophages mediated by nanocarriers. The ELVIS (extravasation through leaky vasculature and inflammatory cell-mediated sequestration) effect associated with arthritis is advantageous in drug delivery. Simply put, the ELVIS effect refers to the extravasation of nanocarriers through leaky vasculatures, which finally results in the accumulation of nanocarriers in the joint cavity.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 1","pages":"Article 101012"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143336437","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}
In the current transformative era of biomedicine, hydrogels have established their presence in biomaterials due to their superior biocompatibility, tuneability and resemblance with native tissue. However, hydrogels typically exhibit poor conductivity due to their hydrophilic polymer structure. Electrical conductivity provides an important enhancement to the properties of hydrogel-based systems in various biomedical applications such as drug delivery and tissue engineering. Consequently, researchers are developing combinatorial strategies to develop electrically responsive “SMART” systems to improve the therapeutic efficacy of biomolecules. Electrically conductive hydrogels have been explored for various drug delivery applications, enabling higher loading of therapeutic cargo with on-demand delivery. This review emphasizes the properties, mechanisms, fabrication techniques and recent advancements of electrically responsive “SMART” systems aiding on-site drug delivery applications. Additionally, it covers prospects for the successful translation of these systems into clinical research.
{"title":"Electrically conductive “SMART” hydrogels for on-demand drug delivery","authors":"Soumajyoti Ghosh , Nikhil Kumar , Santanu Chattopadhyay","doi":"10.1016/j.ajps.2024.101007","DOIUrl":"10.1016/j.ajps.2024.101007","url":null,"abstract":"<div><div>In the current transformative era of biomedicine, hydrogels have established their presence in biomaterials due to their superior biocompatibility, tuneability and resemblance with native tissue. However, hydrogels typically exhibit poor conductivity due to their hydrophilic polymer structure. Electrical conductivity provides an important enhancement to the properties of hydrogel-based systems in various biomedical applications such as drug delivery and tissue engineering. Consequently, researchers are developing combinatorial strategies to develop electrically responsive “SMART” systems to improve the therapeutic efficacy of biomolecules. Electrically conductive hydrogels have been explored for various drug delivery applications, enabling higher loading of therapeutic cargo with on-demand delivery. This review emphasizes the properties, mechanisms, fabrication techniques and recent advancements of electrically responsive “SMART” systems aiding on-site drug delivery applications. Additionally, it covers prospects for the successful translation of these systems into clinical research.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 1","pages":"Article 101007"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143102268","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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