Pub Date : 2025-04-21DOI: 10.1016/j.ajps.2025.101060
Jasleen Kaur , Abhishek Thakran , Saba Naqvi
Neuroinflammation, α-synuclein pathology and dopaminergic cell loss are the hallmarks of Parkinson’s disease (PD), an incurable movement disorder. The presence of the blood-brain barrier (BBB) impedes the delivery of therapeutics and makes the design of drug-targeting delivery vehicles challenging. Nanomedicine is designed and has significantly impacted the scientific community. Over the last few decades, to address the shortcomings of synthetic nanoparticles, a new approach has emerged that mimic the physiological environment. Cell membrane-coated nanoparticles have been developed to interact with the physiological environment, enhance central nervous system drug delivery and mask toxic effects. Cell membranes are multifunctional, biocompatible platforms with the potential for surface modification and targeted delivery design. A synchronous design of cell membrane and nanoparticles is required for the cell membrane-based biomimetics, which can improve the BBB recognition and transport. This review summarizes the challenges in drug delivery and how cell membrane-coated nanoparticles can overcome them. Moreover, major cell membranes used in biomedical applications are discussed with a focus on PD.
{"title":"Recent advances in cell membrane-based biomimetic delivery systems for Parkinson’s disease: Perspectives and challenges","authors":"Jasleen Kaur , Abhishek Thakran , Saba Naqvi","doi":"10.1016/j.ajps.2025.101060","DOIUrl":"10.1016/j.ajps.2025.101060","url":null,"abstract":"<div><div>Neuroinflammation, α-synuclein pathology and dopaminergic cell loss are the hallmarks of Parkinson’s disease (PD), an incurable movement disorder. The presence of the blood-brain barrier (BBB) impedes the delivery of therapeutics and makes the design of drug-targeting delivery vehicles challenging. Nanomedicine is designed and has significantly impacted the scientific community. Over the last few decades, to address the shortcomings of synthetic nanoparticles, a new approach has emerged that mimic the physiological environment. Cell membrane-coated nanoparticles have been developed to interact with the physiological environment, enhance central nervous system drug delivery and mask toxic effects. Cell membranes are multifunctional, biocompatible platforms with the potential for surface modification and targeted delivery design. A synchronous design of cell membrane and nanoparticles is required for the cell membrane-based biomimetics, which can improve the BBB recognition and transport. This review summarizes the challenges in drug delivery and how cell membrane-coated nanoparticles can overcome them. Moreover, major cell membranes used in biomedical applications are discussed with a focus on PD.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 4","pages":"Article 101060"},"PeriodicalIF":11.9,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-18DOI: 10.1016/j.ajps.2025.101056
Qinying Chen , Xinao Liu , Zijin Tan , Zhihao Liu , Zijie Qiu , Yerong Xiong , Jiasheng Tu , Yanping Wu , Chunmeng Sun
Antitumor nanomedicines are usually decorated with ligands to achieve multiple functions, such as targeting delivery, tissue penetration and enhanced cellular uptake. However, a single ligand with multiple functions is generally preferred for use in practice. Herein, a versatile peptide, (HE)10G5R6GDK (HE-RK), was engineered by integrating several motifs into a single sequence, including a masking segment (HE), a flexible linker (G5), and a tumor-penetrating head (RK) which comprised a cell-penetrating peptide (R6) and a C-end Rule peptide (RGDK). The RK moiety in HE-RK was sequentially activated following the gradual charge reversal of HE to facilitate the accumulation of its cargos in deep tumor tissue and the cytosol of cancer cells. Moreover, in our study, polymer micelles conjugated with the HE-RK peptide (PM-HE-RK) showed superior cellular internalization at pH 6.5 compared to pH 7.4 in vitro, as well as extended blood circulation time and improved tumor targeting and penetration in vivo. Furthermore, the paclitaxel-loaded micelles (PTX/PM-HE-RK) demonstrated considerable antitumor efficacy, with an 81.48% tumor inhibition rate in the 4T1 mouse model. Overall, the construction of this all-in-one multisegment peptide presents a synergistic and complementary approach to advancing multifunctional peptide ligand design.
{"title":"All-in-one peptide with sequential pH gradient sensing capabilities for the targeted delivery and deep penetration of nanomicelles against breast cancer","authors":"Qinying Chen , Xinao Liu , Zijin Tan , Zhihao Liu , Zijie Qiu , Yerong Xiong , Jiasheng Tu , Yanping Wu , Chunmeng Sun","doi":"10.1016/j.ajps.2025.101056","DOIUrl":"10.1016/j.ajps.2025.101056","url":null,"abstract":"<div><div>Antitumor nanomedicines are usually decorated with ligands to achieve multiple functions, such as targeting delivery, tissue penetration and enhanced cellular uptake. However, a single ligand with multiple functions is generally preferred for use in practice. Herein, a versatile peptide, (HE)<sub>10</sub>G<sub>5</sub>R<sub>6</sub>GDK (HE-RK), was engineered by integrating several motifs into a single sequence, including a masking segment (HE), a flexible linker (G<sub>5</sub>), and a tumor-penetrating head (RK) which comprised a cell-penetrating peptide (R<sub>6</sub>) and a C-end Rule peptide (RGDK). The RK moiety in HE-RK was sequentially activated following the gradual charge reversal of HE to facilitate the accumulation of its cargos in deep tumor tissue and the cytosol of cancer cells. Moreover, in our study, polymer micelles conjugated with the HE-RK peptide (PM-HE-RK) showed superior cellular internalization at pH 6.5 compared to pH 7.4 <em>in vitro</em>, as well as extended blood circulation time and improved tumor targeting and penetration <em>in vivo</em>. Furthermore, the paclitaxel-loaded micelles (PTX/PM-HE-RK) demonstrated considerable antitumor efficacy, with an 81.48% tumor inhibition rate in the 4T1 mouse model. Overall, the construction of this all-in-one multisegment peptide presents a synergistic and complementary approach to advancing multifunctional peptide ligand design.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 4","pages":"Article 101056"},"PeriodicalIF":11.9,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-16DOI: 10.1016/j.ajps.2025.101057
Bingcheng Yi , Lei Yu , Yating Yang , Carlos F. Guimarães , Ruijie Xu , Thavasyappan Thambi , Boya Zhou , Qihui Zhou , Rui L. Reis
Efficient reconstruction of severe cutaneous wounds necessitates the orchestration of effective cell-mediated matrix remodeling and robust protection against microbial invasion. Herein, we engineered a near-infrared light (NIR)-stimulated, thermo-responsive bilayer system based on a drug-loaded hydrogel with a thermal-responsive temperature of ∼42 °C as the matrix layer and an antibacterial nanofibrous mat as the top layer. The matrix layer integrates basic fibroblast growth factor (bFGF)-loaded thermosensitive gelatin (Gel) hydrogel with polydopamine-Cu2+ coated short nanofibers (P@SF). Upon NIR exposure, P@SF elicits a photothermal effect, causing a rapid increase in temperature by 13.4 °C within 1 min at a power density of 0.75 W/cm2, which triggers the gel-sol transition of Gel and controls the release of bFGF. This, in turn, enhances fibroblast and endothelial cells ingrowth into the hydrogel, fostering cell functionalization and matrix remodeling. The top layer consists of poly(L-lactide-co-caprolactone) nanofibers functionalized with lysine-doped polydopamine and poly-l-lysine. It possesses antibacterial efficacy by isolating, controlling (76.23% for E. coli and 89.16% for S. aureus), and eliminating bacteria upon NIR activation. In rat skin wound models, this NIR-responsive smart bilayer system prevents S. aureus-mediated bacterial infection (indicative of reduced IL-6 expression), regulates CD31-positive neovascularization, and facilitates collagen remodeling for skin regeneration. In summary, this study introduces a novel strategy, inspired by the centralization of authority, for developing a smart thermo-responsive system with promising potential for the effective reconstruction of severe cutaneous wounds.
{"title":"Light-stimulated smart thermo-responsive constructs for enhanced wound healing: A streamlined command approach","authors":"Bingcheng Yi , Lei Yu , Yating Yang , Carlos F. Guimarães , Ruijie Xu , Thavasyappan Thambi , Boya Zhou , Qihui Zhou , Rui L. Reis","doi":"10.1016/j.ajps.2025.101057","DOIUrl":"10.1016/j.ajps.2025.101057","url":null,"abstract":"<div><div>Efficient reconstruction of severe cutaneous wounds necessitates the orchestration of effective cell-mediated matrix remodeling and robust protection against microbial invasion. Herein, we engineered a near-infrared light (NIR)-stimulated, thermo-responsive bilayer system based on a drug-loaded hydrogel with a thermal-responsive temperature of ∼42 °C as the matrix layer and an antibacterial nanofibrous mat as the top layer. The matrix layer integrates basic fibroblast growth factor (bFGF)-loaded thermosensitive gelatin (Gel) hydrogel with polydopamine-Cu<sup>2+</sup> coated short nanofibers (P@SF). Upon NIR exposure, P@SF elicits a photothermal effect, causing a rapid increase in temperature by 13.4 °C within 1 min at a power density of 0.75 W/cm<sup>2</sup>, which triggers the gel-sol transition of Gel and controls the release of bFGF. This, in turn, enhances fibroblast and endothelial cells ingrowth into the hydrogel, fostering cell functionalization and matrix remodeling. The top layer consists of poly(L-lactide-co-caprolactone) nanofibers functionalized with lysine-doped polydopamine and poly-<span>l</span>-lysine. It possesses antibacterial efficacy by isolating, controlling (76.23% for <em>E. coli</em> and 89.16% for <em>S. aureus</em>), and eliminating bacteria upon NIR activation. In rat skin wound models, this NIR-responsive smart bilayer system prevents <em>S. aureus</em>-mediated bacterial infection (indicative of reduced IL-6 expression), regulates CD31-positive neovascularization, and facilitates collagen remodeling for skin regeneration. In summary, this study introduces a novel strategy, inspired by the centralization of authority, for developing a smart thermo-responsive system with promising potential for the effective reconstruction of severe cutaneous wounds.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 4","pages":"Article 101057"},"PeriodicalIF":11.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-03DOI: 10.1016/j.ajps.2025.101052
Zhifei Cheng , Wengui Lu , Wei Shao , Chuan Zhang , Yunfei She , Rui Song , Ruohan Qi , Jiajia Song , Wenjing Zhang , Xiangwei Chang , Ning Wang , Qi Liu , Shuangying Gui , Qi Wang
Dysregulated inflammatory reactions can result in detrimental effects to the body, thereby causing various diseases. Traditional treatments relying on anti-inflammatory drugs or nanoformulations often undermine the body's physiological immune functions or potentially exhibit biotoxicity. Extracellular vesicles, which contain a diverse array of anti-inflammatory substances and possess nanomedicine transport properties, are emerging as highly promising candidates for next-generation drug delivery systems and active biological agents. Plant-derived vesicle-like nanoparticles (PDVLNs) are nanostructured particles isolated from plants. Given their wide availability and low immunogenicity, PDVLNs are considered to hold great potential in the treatment of inflammatory diseases (IDs). In this review, we introduce the principle, design consideration and treatment mechanism associated with PDVLNs in treating various IDs. Specifically, the natural ingredients carried by PDVLNs not only help eliminate danger signals such as reactive oxygen species and reactive nitrogen species, but also hinder the initiation of inflammatory responses through various mechanisms. Moreover, engineered PDVLNs nanotechnology has been successfully employed in the treatment of IDs. Finally, the review discusses the current opportunities and challenges in this field and provides insights for the future clinical applications of PDVLNs in treating IDs.
{"title":"Advances in plant-derived vesicle like nanoparticles-based therapies for inflammatory diseases","authors":"Zhifei Cheng , Wengui Lu , Wei Shao , Chuan Zhang , Yunfei She , Rui Song , Ruohan Qi , Jiajia Song , Wenjing Zhang , Xiangwei Chang , Ning Wang , Qi Liu , Shuangying Gui , Qi Wang","doi":"10.1016/j.ajps.2025.101052","DOIUrl":"10.1016/j.ajps.2025.101052","url":null,"abstract":"<div><div>Dysregulated inflammatory reactions can result in detrimental effects to the body, thereby causing various diseases. Traditional treatments relying on anti-inflammatory drugs or nanoformulations often undermine the body's physiological immune functions or potentially exhibit biotoxicity. Extracellular vesicles, which contain a diverse array of anti-inflammatory substances and possess nanomedicine transport properties, are emerging as highly promising candidates for next-generation drug delivery systems and active biological agents. Plant-derived vesicle-like nanoparticles (PDVLNs) are nanostructured particles isolated from plants. Given their wide availability and low immunogenicity, PDVLNs are considered to hold great potential in the treatment of inflammatory diseases (IDs). In this review, we introduce the principle, design consideration and treatment mechanism associated with PDVLNs in treating various IDs. Specifically, the natural ingredients carried by PDVLNs not only help eliminate danger signals such as reactive oxygen species and reactive nitrogen species, but also hinder the initiation of inflammatory responses through various mechanisms. Moreover, engineered PDVLNs nanotechnology has been successfully employed in the treatment of IDs. Finally, the review discusses the current opportunities and challenges in this field and provides insights for the future clinical applications of PDVLNs in treating IDs.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 4","pages":"Article 101052"},"PeriodicalIF":11.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-30DOI: 10.1016/j.ajps.2025.101053
Liting Cheng , Zhongyi Ma , Xinlin Yang , Xue Wang , Yuqiong Wang , Xinlong Liu , Zhongjie Tang , Dingxi Jang , Guojian Liao , Tongbao Liu , Shuang Wu , Chong Li
Cryptococcosis, a serious systemic fungal infection caused by Cryptococcus neoformans (C. neoformans) and its variants, poses a significant clinical challenge due to its poor prognosis and severe health implications. The treatment of cryptococcal infections is complicated by several unique factors, stemming from both the pathogenic characteristics of the fungi and the biological barriers they exploit. These include the fungi's protective capsule, their ability to reside within host macrophages—thereby evading pharmacological intervention—and their involvement in multi-organ infections such as the lung and brain, in particular their strategic positioning within the brain, protected by the blood-brain barrier (BBB). To overcome these obstacles, precise active targeting emerges as a pivotal strategy. Identifying common targets is imperative to enhance therapeutic efficacy while ensuring the druggability of delivery systems. However, research on the methodology for selecting such shared targets remains sparse. In our investigation, we have pioneered the use of secreted proteins as shared target to trace the pathogens and their infection pathways. We identified the mannoprotein Cig1, prominently expressed on the surfaces of infected macrophages, lungs, and brains, as a viable shared target. On this basis, we utilized Hemin, a ligand for Cig1, to design liposomes (Hemin Lip) tailored for addressing complex fungal infections. By leveraging the interaction with the secreted protein Cig1, Hemin Lip specifically identifies and binds to organs and macrophages harboring cryptococcal infections, thereby facilitating targeted and efficacious clearance of both intracellular and extracellular fungus. Moreover, we have extended this targeting mechanism to other nanomedicinal platforms, including albumin nanoparticles. This study proposes an innovative drug delivery model that targets extracellular secretory proteins within the infection microenvironment, offering a streamlined formulation with the potential for effective therapy against complex infections.
{"title":"All-stage targeted therapy for invasive cryptococcosis through interaction between the secretory protein Cig1 and hemin","authors":"Liting Cheng , Zhongyi Ma , Xinlin Yang , Xue Wang , Yuqiong Wang , Xinlong Liu , Zhongjie Tang , Dingxi Jang , Guojian Liao , Tongbao Liu , Shuang Wu , Chong Li","doi":"10.1016/j.ajps.2025.101053","DOIUrl":"10.1016/j.ajps.2025.101053","url":null,"abstract":"<div><div>Cryptococcosis, a serious systemic fungal infection caused by <em>Cryptococcus neoformans</em> (<em>C. neoformans</em>) and its variants, poses a significant clinical challenge due to its poor prognosis and severe health implications. The treatment of cryptococcal infections is complicated by several unique factors, stemming from both the pathogenic characteristics of the fungi and the biological barriers they exploit. These include the fungi's protective capsule, their ability to reside within host macrophages—thereby evading pharmacological intervention—and their involvement in multi-organ infections such as the lung and brain, in particular their strategic positioning within the brain, protected by the blood-brain barrier (BBB). To overcome these obstacles, precise active targeting emerges as a pivotal strategy. Identifying common targets is imperative to enhance therapeutic efficacy while ensuring the druggability of delivery systems. However, research on the methodology for selecting such shared targets remains sparse. In our investigation, we have pioneered the use of secreted proteins as shared target to trace the pathogens and their infection pathways. We identified the mannoprotein Cig1, prominently expressed on the surfaces of infected macrophages, lungs, and brains, as a viable shared target. On this basis, we utilized Hemin, a ligand for Cig1, to design liposomes (Hemin Lip) tailored for addressing complex fungal infections. By leveraging the interaction with the secreted protein Cig1, Hemin Lip specifically identifies and binds to organs and macrophages harboring cryptococcal infections, thereby facilitating targeted and efficacious clearance of both intracellular and extracellular fungus. Moreover, we have extended this targeting mechanism to other nanomedicinal platforms, including albumin nanoparticles. This study proposes an innovative drug delivery model that targets extracellular secretory proteins within the infection microenvironment, offering a streamlined formulation with the potential for effective therapy against complex infections.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 4","pages":"Article 101053"},"PeriodicalIF":11.9,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Microneedle-mediated drug delivery systems (MDDS) have experienced robust growth in recent years, with designers leveraging their creativity to apply these systems for direct drug delivery to the skin, mucous membranes, blood vessel walls and even internal organs. In order to achieve precise drug delivery, various delicately conceived drug release modes based on MDDS have been developed. Herein, to elucidate the design concepts of numerous reported MDDS, we have categorized them into two levels (Level-Ⅰ MDDS and Level-Ⅱ MDDS) depending on whether nanoscale and microscale carriers are integrated within the microneedles. In this work, the design strategies of MDDS, as well as the current status of their applications in targeted and intelligent drug delivery were reviewed, while their prospects and challenges for future industrialization and clinical applications were also discussed.
{"title":"Progressive microneedles for targeting and intelligent drug delivery","authors":"Jiaqi Li, Qing Xia, Shuwen Ma, Zhi Wang, Teng Guo, Nianping Feng, Yongtai Zhang","doi":"10.1016/j.ajps.2025.101051","DOIUrl":"10.1016/j.ajps.2025.101051","url":null,"abstract":"<div><div>Microneedle-mediated drug delivery systems (MDDS) have experienced robust growth in recent years, with designers leveraging their creativity to apply these systems for direct drug delivery to the skin, mucous membranes, blood vessel walls and even internal organs. In order to achieve precise drug delivery, various delicately conceived drug release modes based on MDDS have been developed. Herein, to elucidate the design concepts of numerous reported MDDS, we have categorized them into two levels (Level-Ⅰ MDDS and Level-Ⅱ MDDS) depending on whether nanoscale and microscale carriers are integrated within the microneedles. In this work, the design strategies of MDDS, as well as the current status of their applications in targeted and intelligent drug delivery were reviewed, while their prospects and challenges for future industrialization and clinical applications were also discussed.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 3","pages":"Article 101051"},"PeriodicalIF":10.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-14DOI: 10.1016/j.ajps.2025.101043
Jun Quan Ng , Nabil Ajwad Abu Yazid , Shing Cheng Tan , Mastura Monif , Tin Wui Wong , Si-Yuen Lee
Current treatments for glioblastoma face challenges such as the blood-brain barrier and lack of targeted therapy, compounded by the aggressive nature, high invasiveness, and heterogeneity of the disease. Exosomes, a subtype of extracellular vesicles are emerging as promising nanocarrier drug delivery systems to address these limitations. Exosomes released by all cell types can be easily obtained and modified as delivery vehicles or therapeutic agents. A systematic review was conducted to evaluate various methods for exosome isolation, characterization, engineering or modification, drug loading and delivery efficiency, including exosome biodistribution and treatment efficacy. A search of four databases for in vitro and in vivo studies (2000–,2023) identified 6165 records, of which 23 articles were found eligible and included for analyses. Most studies applied ultracentrifugation (UC) for exosomes isolation. Cancer cell lines being the most frequently used source of exosomes, followed by stem cells. The incubation approach was predominantly utilized to modify exosomes for drug loading. In vivo analysis showed that exosome biodistribution was primarily concentrated in the brain region, peaking in the first 6 h and remained moderately high. Compared to native exosomes and untreated control groups, utilizing modified native exosomes (cargo loaded) for treating glioblastoma disease models led to more pronounced suppression of tumor growth and proliferation, enhanced stimulation of immune response and apoptosis, effective restoration of drug chemosensitivity, increased anti-tumor effect and prolonged survival rates. Modified exosomes whether through incubation, sonication, transfection, freeze-thawing or their combination, improve targeted delivery and therapeutic efficacy against glioblastoma.
{"title":"Extracellular vesicles as delivery vehicles and therapeutic agents for glioblastoma treatment: A systematic review of in vitro and in vivo preclinical studies","authors":"Jun Quan Ng , Nabil Ajwad Abu Yazid , Shing Cheng Tan , Mastura Monif , Tin Wui Wong , Si-Yuen Lee","doi":"10.1016/j.ajps.2025.101043","DOIUrl":"10.1016/j.ajps.2025.101043","url":null,"abstract":"<div><div>Current treatments for glioblastoma face challenges such as the blood-brain barrier and lack of targeted therapy, compounded by the aggressive nature, high invasiveness, and heterogeneity of the disease. Exosomes, a subtype of extracellular vesicles are emerging as promising nanocarrier drug delivery systems to address these limitations. Exosomes released by all cell types can be easily obtained and modified as delivery vehicles or therapeutic agents. A systematic review was conducted to evaluate various methods for exosome isolation, characterization, engineering or modification, drug loading and delivery efficiency, including exosome biodistribution and treatment efficacy. A search of four databases for <em>in vitro</em> and <em>in vivo</em> studies (2000–,2023) identified 6165 records, of which 23 articles were found eligible and included for analyses. Most studies applied ultracentrifugation (UC) for exosomes isolation. Cancer cell lines being the most frequently used source of exosomes, followed by stem cells. The incubation approach was predominantly utilized to modify exosomes for drug loading. In vivo analysis showed that exosome biodistribution was primarily concentrated in the brain region, peaking in the first 6 h and remained moderately high. Compared to native exosomes and untreated control groups, utilizing modified native exosomes (cargo loaded) for treating glioblastoma disease models led to more pronounced suppression of tumor growth and proliferation, enhanced stimulation of immune response and apoptosis, effective restoration of drug chemosensitivity, increased anti-tumor effect and prolonged survival rates. Modified exosomes whether through incubation, sonication, transfection, freeze-thawing or their combination, improve targeted delivery and therapeutic efficacy against glioblastoma.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 3","pages":"Article 101043"},"PeriodicalIF":10.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-26DOI: 10.1016/j.ajps.2025.101041
Asif Nawaz , Nur Syamimi Ariffin , Tin Wui Wong
CRISPR-Cas system permanently deletes any harmful gene-of-interest to combat cancer growth. Chitosan (CS) is a potential cancer therapeutic that mediates via PI3K/Akt/mTOR, MAPK and NF-kβ signaling pathway modulation. CS and its covalent derivatives have been designed as nanocarrier of CRISPR-Cas9 alone (plasmid or ribonucleoprotein) or in combination with chemical drug for cancer treatment. The nanocarrier was functionalized with polyethylene glycol (PEG), targeting ligand, cell penetrating ligand and its inherent positive zeta potential to mitigate premature clearance and particulate aggregation, and promote cancer cell/nucleus targeting and permeabilization to enable CRISPR-Cas9 acting on the host DNA. Different physicochemical attributes are required for the CS-based nanocarrier to survive from the administration site, through the systemic circulation-extracellular matrix-mucus-mucosa axis, to the nucleus target. CRISPR-Cas9 delivery is met with heterogeneous uptake by the cancer cells. Choice of excipients such as targeting ligand and PEG may be inappropriate due to lacking overexpressed cancer receptor or availability of excessive metabolizing enzyme and immunoglobulin that defies the survival and action of these excipients rendering nanocarrier fails to reach the target site. Cancer omics analysis should be implied to select excipients which meet the pathophysiological needs, and chitosan nanocarrier with a “transformative physicochemical behavior” is essential to succeed CRISPR-Cas9 delivery.
{"title":"Functionalized chitosan as nano-delivery platform for CRISPR-Cas9 in cancer treatment","authors":"Asif Nawaz , Nur Syamimi Ariffin , Tin Wui Wong","doi":"10.1016/j.ajps.2025.101041","DOIUrl":"10.1016/j.ajps.2025.101041","url":null,"abstract":"<div><div>CRISPR-Cas system permanently deletes any harmful gene-of-interest to combat cancer growth. Chitosan (CS) is a potential cancer therapeutic that mediates via PI3K/Akt/mTOR, MAPK and NF-kβ signaling pathway modulation. CS and its covalent derivatives have been designed as nanocarrier of CRISPR-Cas9 alone (plasmid or ribonucleoprotein) or in combination with chemical drug for cancer treatment. The nanocarrier was functionalized with polyethylene glycol (PEG), targeting ligand, cell penetrating ligand and its inherent positive zeta potential to mitigate premature clearance and particulate aggregation, and promote cancer cell/nucleus targeting and permeabilization to enable CRISPR-Cas9 acting on the host DNA. Different physicochemical attributes are required for the CS-based nanocarrier to survive from the administration site, through the systemic circulation-extracellular matrix-mucus-mucosa axis, to the nucleus target. CRISPR-Cas9 delivery is met with heterogeneous uptake by the cancer cells. Choice of excipients such as targeting ligand and PEG may be inappropriate due to lacking overexpressed cancer receptor or availability of excessive metabolizing enzyme and immunoglobulin that defies the survival and action of these excipients rendering nanocarrier fails to reach the target site. Cancer omics analysis should be implied to select excipients which meet the pathophysiological needs, and chitosan nanocarrier with a “transformative physicochemical behavior” is essential to succeed CRISPR-Cas9 delivery.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 3","pages":"Article 101041"},"PeriodicalIF":10.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cellular hitchhiking is an emerging therapeutic strategy that uses an endogenous cell migration mechanism to deliver therapeutics to specific sites in the body. Owing to the low permeability and presence of the blood-brain barrier (BBB), the targeted delivery of therapeutics is limited, leading to inadequate localization in the brain. NCs fail to extravasate significantly into the tumor microenvironment (TME), demonstrating poor accumulation and tumor penetration. The novel cellular hitchhiking concept has been utilized to promote systemic half-life and therapeutic targeting. Neoplastic and neuroinflammatory diseases of the brain, including glioblastoma and neuroinflammation, face critical hurdles for efficiently delivering therapeutic entities owing to the BBB. Cellular hitchhiking can surmount these hurdles by utilizing various cell populations, such as stem cells, monocytes/macrophages, neutrophils, and platelets, as potential functional carriers to deliver the therapeutic cargo through the BBB. These carrier cells have the innate capability to traverse the BBB, transit through the brain parenchyma, and specifically reach disease sites such as inflammatory and neoplastic lesions owing to chemotactic navigation, i.e., movement attributed to chemical stimuli. Chemotherapeutic drugs delivered by cellular hitchhiking to achieve tumor-specific targeting have been discussed. This article explores various cell types for hitchhiking NCs to the TME with in-depth mechanisms and characterization techniques to decipher the backpack dissociation dynamics (nanoparticle payload detachment characteristics from hitchhiked cells) and challenges toward prospective clinical translation.
{"title":"Navigating the brain: Harnessing endogenous cellular hitchhiking for targeting neoplastic and neuroinflammatory diseases","authors":"Suraj S. Wagh , Paras Famta , Saurabh Shah , Ganesh Vambhurkar , Giriraj Pandey , Anupama Sikder , Gurpreet Singh , Shalini Shukla , Abhishek Sharma , Sajja Bhanu Prasad , Akshay Shinde , Rahul Kumar , Nitin Pal Kalia , Rajeev Singh Raghuvanshi , Saurabh Srivastava","doi":"10.1016/j.ajps.2025.101040","DOIUrl":"10.1016/j.ajps.2025.101040","url":null,"abstract":"<div><div>Cellular hitchhiking is an emerging therapeutic strategy that uses an endogenous cell migration mechanism to deliver therapeutics to specific sites in the body. Owing to the low permeability and presence of the blood-brain barrier (BBB), the targeted delivery of therapeutics is limited, leading to inadequate localization in the brain. NCs fail to extravasate significantly into the tumor microenvironment (TME), demonstrating poor accumulation and tumor penetration. The novel cellular hitchhiking concept has been utilized to promote systemic half-life and therapeutic targeting. Neoplastic and neuroinflammatory diseases of the brain, including glioblastoma and neuroinflammation, face critical hurdles for efficiently delivering therapeutic entities owing to the BBB. Cellular hitchhiking can surmount these hurdles by utilizing various cell populations, such as stem cells, monocytes/macrophages, neutrophils, and platelets, as potential functional carriers to deliver the therapeutic cargo through the BBB. These carrier cells have the innate capability to traverse the BBB, transit through the brain parenchyma, and specifically reach disease sites such as inflammatory and neoplastic lesions owing to chemotactic navigation, <em>i.e.</em>, movement attributed to chemical stimuli. Chemotherapeutic drugs delivered by cellular hitchhiking to achieve tumor-specific targeting have been discussed. This article explores various cell types for hitchhiking NCs to the TME with in-depth mechanisms and characterization techniques to decipher the backpack dissociation dynamics (nanoparticle payload detachment characteristics from hitchhiked cells) and challenges toward prospective clinical translation.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 2","pages":"Article 101040"},"PeriodicalIF":10.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143637575","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}
Mimicking the hierarchical structure of the skin is one of the most important strategies in skin tissue engineering. Monolayer wound dressings are usually not able to provide several functions at the same time and cannot meet all clinical needs. In order to maximize therapeutic efficiency, herein, we fabricated a Tri-layer wound dressing, where the middle layer was fabricated via 3D-printing and composed of alginate, tragacanth and zinc oxide nanoparticles (ZnO NPs). Both upper and bottom layers were constructed using electrospinning technique; the upper layer was made of hydrophobic polycaprolactone to mimic epidermis, while the bottom layer consisted of Soluplus® and insulin-like growth factor-1 (IGF-1) to promote cell behavior. Swelling, water vapor permeability and tensile properties of the dressings were evaluated and the Tri-layer dressing exhibited impressive antibacterial activity and cell stimulation following by the release of ZnO NPs and IGF-1. Additionally, the Tri-layer dressing led to faster healing of full-thickness wound in rat model compared to monolayer and Bilayer dressings. Overall, the evidence confirmed that the Tri-layer wound dressing is extremely effective for full-thickness wound healing.
{"title":"Multifunctional tri-layer wound dressing containing ZNO nanoparticles and IGF-1 as an efficient biomaterial for healing of full thickness skin injuries","authors":"Azin Abedi Koupai , Jaleh Varshosaz , Mohamadreza Tavakoli , Marjan Mirhaj , Saeideh Salehi , Faramarz Dobakhti","doi":"10.1016/j.ajps.2025.101039","DOIUrl":"10.1016/j.ajps.2025.101039","url":null,"abstract":"<div><div>Mimicking the hierarchical structure of the skin is one of the most important strategies in skin tissue engineering. Monolayer wound dressings are usually not able to provide several functions at the same time and cannot meet all clinical needs. In order to maximize therapeutic efficiency, herein, we fabricated a Tri-layer wound dressing, where the middle layer was fabricated via 3D-printing and composed of alginate, tragacanth and zinc oxide nanoparticles (ZnO NPs). Both upper and bottom layers were constructed using electrospinning technique; the upper layer was made of hydrophobic polycaprolactone to mimic epidermis, while the bottom layer consisted of Soluplus® and insulin-like growth factor-1 (IGF-1) to promote cell behavior. Swelling, water vapor permeability and tensile properties of the dressings were evaluated and the Tri-layer dressing exhibited impressive antibacterial activity and cell stimulation following by the release of ZnO NPs and IGF-1. Additionally, the Tri-layer dressing led to faster healing of full-thickness wound in rat model compared to monolayer and Bilayer dressings. Overall, the evidence confirmed that the Tri-layer wound dressing is extremely effective for full-thickness wound healing.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 3","pages":"Article 101039"},"PeriodicalIF":10.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144072737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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