Asian Journal of Pharmaceutical Sciences最新文献_第10页

Nano transdermal system combining mitochondria-targeting cerium oxide nanoparticles with all-trans retinoic acid for psoriasis 结合线粒体靶向氧化铈纳米颗粒与全反式维甲酸治疗银屑病的纳米透皮系统

IF 10.2 1区医学

Asian Journal of Pharmaceutical Sciences Pub Date : 2023-09-01 DOI: 10.1016/j.ajps.2023.100846

Wei Wang , Xinyi Xu , Yanling Song , Lan Lan , Jun Wang , Xinchang Xu , Yongzhong Du

{"title":"Nano transdermal system combining mitochondria-targeting cerium oxide nanoparticles with all-trans retinoic acid for psoriasis","authors":"Wei Wang , Xinyi Xu , Yanling Song , Lan Lan , Jun Wang , Xinchang Xu , Yongzhong Du","doi":"10.1016/j.ajps.2023.100846","DOIUrl":"https://doi.org/10.1016/j.ajps.2023.100846","url":null,"abstract":"<div><p>Psoriasis is an inflammatory skin disease that is intricately linked to oxidative stress. Antioxidation and inhibition of abnormal proliferation of keratinocytes are pivotal strategies for psoriasis. Delivering drugs with these effects to the site of skin lesions is a challenge that needs to be solved. Herein, we reported a nanotransdermal delivery system composed of all-trans retinoic acid (TRA), triphenylphosphine (TPP)-modified cerium oxide (CeO<sub>2</sub>) nanoparticles, flexible nanoliposomes and gels (TCeO<sub>2</sub>-TRA-FNL-Gel). The results revealed that TCeO<sub>2</sub> synthesized by the anti-micelle method, with a size of approximately 5 nm, possessed excellent mitochondrial targeting ability and valence conversion capability related to scavenging reactive oxygen species (ROS). TCeO<sub>2</sub>-TRA-FNL prepared by the film dispersion method, with a size of approximately 70 nm, showed high drug encapsulation efficiency (>96%). TCeO<sub>2</sub>-TRA-FNL-Gel further showed sustained drug release behaviors, great transdermal permeation ability, and greater skin retention than the free TRA. The results of <em>in vitro</em> EGF-induced and H<sub>2</sub>O<sub>2</sub>-induced models suggested that TCeO<sub>2</sub>-TRA-FNL effectively reduced the level of inflammation and alleviated oxidative stress in HaCat cells. The results of <em>in vivo</em> imiquimod (IMQ)-induced model indicated that TCeO<sub>2</sub>-TRA-FNL-Gel could greatly alleviate the psoriasis symptoms. In summary, the transdermal drug delivery system designed in this study has shown excellent therapeutic effects on psoriasis and is prospective for the safe and accurate therapy of psoriasis.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 5","pages":"Article 100846"},"PeriodicalIF":10.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49709938","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}

引用次数: 0

Biomimetic biomineralization nanoplatform-mediated differentiation therapy and phototherapy for cancer stem cell inhibition and antitumor immunity activation 仿生生物矿化纳米平台介导的分化和光疗对肿瘤干细胞抑制和抗肿瘤免疫激活的作用

IF 10.2 1区医学

Asian Journal of Pharmaceutical Sciences Pub Date : 2023-09-01 DOI: 10.1016/j.ajps.2023.100851

Shan Gao, Meng Liu, Dongzhu Liu, Xinru Kong, Yuelin Fang, Yingying Li, Hang Wu, Jianbo Ji, Xiaoye Yang, Guangxi Zhai

{"title":"Biomimetic biomineralization nanoplatform-mediated differentiation therapy and phototherapy for cancer stem cell inhibition and antitumor immunity activation","authors":"Shan Gao, Meng Liu, Dongzhu Liu, Xinru Kong, Yuelin Fang, Yingying Li, Hang Wu, Jianbo Ji, Xiaoye Yang, Guangxi Zhai","doi":"10.1016/j.ajps.2023.100851","DOIUrl":"https://doi.org/10.1016/j.ajps.2023.100851","url":null,"abstract":"<div><p>Growing evidence suggests that the presence of cancer stem cells (CSCs) is a major challenge in current tumor treatments, especially the transition from non-CSCs to differentiation of CSCs for evading conventional therapies and driving metastasis. Here we propose a therapeutic strategy of synergistic differentiation therapy and phototherapy to induce differentiation of CSCs into mature tumor cells by differentiation inducers and synergistic elimination of them and normal cancer cells through phototherapy. In this work, we synthesized a biomimetic nanoplatform loaded with IR-780 and all-trans retinoic acid (ATRA) <em>via</em> biomineralization. This method can integrate aluminum ions into small-sized protein carriers to form nanoclusters, which undergo responsive degradation under acidic conditions and facilitate deep tumor penetration. With the help of CSC differentiation induced by ATRA, IR-780 inhibited the self-renewal of CSCs and cancer progression by generating hyperthermia and reactive oxygen species in a synergistic manner. Furthermore, ATRA can boost immunogenic cell death induced by phototherapy, thereby strongly causing a systemic anti-tumor immune response and efficiently eliminating CSCs and tumor cells. Taken together, this dual strategy represents a new paradigm of targeted eradication of CSCs and tumors by inducing CSC differentiation, improving photothermal therapy/photodynamic therapy and enhancing antitumor immunity.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 5","pages":"Article 100851"},"PeriodicalIF":10.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49709877","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}

引用次数: 0

Low-temperature photothermal-induced alkyl radical release facilitates dihydroartemisinin-triggered “valve-off” starvation therapy 低温光热诱导的烷基自由基释放促进了双氢青蒿素触发的“关阀”饥饿治疗

IF 10.2 1区医学

Asian Journal of Pharmaceutical Sciences Pub Date : 2023-09-01 DOI: 10.1016/j.ajps.2023.100850

Xiaomin Su , Boshu Ouyang , Yao Liu , Yang Wang , Ruizhe Xu , Lili Niu , NanNan Li , Ce Xu , Zanya Sun , Huishu Guo , Zhiqing Pang , Xiangrong Yu

{"title":"Low-temperature photothermal-induced alkyl radical release facilitates dihydroartemisinin-triggered “valve-off” starvation therapy","authors":"Xiaomin Su , Boshu Ouyang , Yao Liu , Yang Wang , Ruizhe Xu , Lili Niu , NanNan Li , Ce Xu , Zanya Sun , Huishu Guo , Zhiqing Pang , Xiangrong Yu","doi":"10.1016/j.ajps.2023.100850","DOIUrl":"https://doi.org/10.1016/j.ajps.2023.100850","url":null,"abstract":"<div><p>The high nutrient and energy demand of tumor cells compared to normal cells to sustain rapid proliferation offer a potentially auspicious avenue for implementing starvation therapy. However, conventional starvation therapy, such as glucose exhaustion and vascular thrombosis, can lead to systemic toxicity and exacerbate tumor hypoxia. Herein, we developed a new “valve-off” starvation tactic, which was accomplished by closing the valve of glucose transporter protein 1 (GLUT1). Specifically, dihydroartemisinin (DHA), 2,20-azobis [2-(2-imidazolin-2-yl) propane] dihydrochloride (AI), and Ink were co-encapsulated in a sodium alginate (ALG) hydrogel. Upon irradiation with the 1064 nm laser, AI rapidly disintegrated into alkyl radicals (R<sup>•</sup>), which exacerbated the DHA-induced mitochondrial damage through the generation of reactive oxygen species and further reduced the synthesis of adenosine triphosphate (ATP). Simultaneously, the production of R<sup>•</sup> facilitated DHA-induced starvation therapy by suppressing GLUT1, which in turn reduced glucose uptake. Systematic <em>in vivo</em> and <em>in vitro</em> results suggested that this radical-enhanced “valve-off” strategy for inducing tumor cell starvation was effective in reducing glucose uptake and ATP levels. This integrated strategy induces tumor starvation with efficient tumor suppression, creating a new avenue for controlled, precise, and concerted tumor therapy.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 5","pages":"Article 100850"},"PeriodicalIF":10.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49709892","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}

引用次数: 0

Targeted hyperalkalization with NaOH-loaded starch implants enhances doxorubicin efficacy in tumor treatment 用NaOH负载的淀粉植入物进行靶向超碱性化可增强阿霉素在肿瘤治疗中的疗效。

IF 10.2 1区医学

Asian Journal of Pharmaceutical Sciences Pub Date : 2023-09-01 DOI: 10.1016/j.ajps.2023.100853

Changkyu Lee

{"title":"Targeted hyperalkalization with NaOH-loaded starch implants enhances doxorubicin efficacy in tumor treatment","authors":"Changkyu Lee","doi":"10.1016/j.ajps.2023.100853","DOIUrl":"10.1016/j.ajps.2023.100853","url":null,"abstract":"<div><p>High-alkali treatment using sodium hydroxide (NaOH) injection can be a therapeutic approach for killing tumor cells. Alkalization can damage cellular structures and lead to cell death. Increased alkalinity can also enhance the efficacy of certain chemotherapeutic drugs such as doxorubicin (DOX). In this study, NaOH-loaded starch implants (NST implants) were used to induce hyperalkalization (increase pH) in the tumor environment, thereby inducing necrosis and enhancing the effects of DOX. NaOH is a strongly alkaline substance that can increase the pH when injected into a tumor. However, the administration of NaOH can have toxic side effects because it increases the pH of the entire body, not just at the tumor site. To overcome this problem, we developed an injectable NST implant, in which NaOH can be delivered directly into the tumor. This study showed that NST implants could be easily administered intratumorally in mice bearing 4T1 tumors and that most of the NaOH released from the NST implants was delivered to the tumors. Although some NaOH from NST implants can be systemically absorbed, it is neutralized by the body's buffering effect, thereby reducing the risk of toxicity. This study also confirmed both <em>in vitro</em> and <em>in vivo</em> that DOX is more effective at killing 4T1 cells when alkalized. It has been shown that administration of DOX after injection of an NST implant can kill most tumors. Systemic absorption and side effects can be reduced using an NST implant to deliver NaOH to the tumor. In addition, alkalinization induced by NST implants not only exerts anticancer effects but can also enhance the effect of DOX in killing cancer cells. Therefore, the combination of NaOH-loaded starch implants and DOX treatment has the potential to be a novel therapy for tumors.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 5","pages":"Article 100853"},"PeriodicalIF":10.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420179","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}

引用次数: 0

Combination therapy to overcome ferroptosis resistance by biomimetic self-assembly nano-prodrug 仿生自组装纳米前药联合治疗抗脱铁性

IF 10.2 1区医学

Asian Journal of Pharmaceutical Sciences Pub Date : 2023-09-01 DOI: 10.1016/j.ajps.2023.100844

Yong Huang , Yi Lin , Bowen Li , Fu Zhang , Chenyue Zhan , Xin Xie , Zhuo Yao , Chongzhi Wu , Yuan Ping , Jianliang Shen

{"title":"Combination therapy to overcome ferroptosis resistance by biomimetic self-assembly nano-prodrug","authors":"Yong Huang , Yi Lin , Bowen Li , Fu Zhang , Chenyue Zhan , Xin Xie , Zhuo Yao , Chongzhi Wu , Yuan Ping , Jianliang Shen","doi":"10.1016/j.ajps.2023.100844","DOIUrl":"10.1016/j.ajps.2023.100844","url":null,"abstract":"<div><p>Ferroptosis has emerged as a potent form of no-apoptotic cell death that offers a promising alternative to avoid the chemoresistance of apoptotic pathways and serves as a vulnerability of cancer. Herein, we have constructed a biomimetic self-assembly nano-prodrug system that enables the co-delivery of gefitinib (Gefi), ferrocene (Fc) and dihydroartemisinin (DHA) for the combined therapy of both ferroptosis and apoptosis. In the tumor microenvironment, this nano-prodrug is able to disassemble and trigger drug release under high levels of GSH. Interestingly, the released DHA can downregulate GPX4 level for the enhancement of intracellular ferroptosis from Fc, further executing tumor cell death with concomitant chemotherapy by Gefi. More importantly, this nano-prodrug provides highly homologous targeting ability by coating related cell membranes and exhibits outstanding inhibition of tumor growth and metastasis, as well as no noticeable side-effects during treatments. This simple small molecular self-assembled nano-prodrug provides a new reasonably designed modality for ferroptosis-combined chemotherapy.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 5","pages":"Article 100844"},"PeriodicalIF":10.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46255679","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}

引用次数: 0

The emerging potential of siRNA nanotherapeutics in treatment of arthritis siRNA纳米疗法在关节炎治疗中的新潜力

IF 10.2 1区医学

Asian Journal of Pharmaceutical Sciences Pub Date : 2023-09-01 DOI: 10.1016/j.ajps.2023.100845

Anjali Kumari , Amanpreet Kaur , Geeta Aggarwal

{"title":"The emerging potential of siRNA nanotherapeutics in treatment of arthritis","authors":"Anjali Kumari , Amanpreet Kaur , Geeta Aggarwal","doi":"10.1016/j.ajps.2023.100845","DOIUrl":"https://doi.org/10.1016/j.ajps.2023.100845","url":null,"abstract":"<div><p>RNA interference (RNAi) using small interfering RNA (siRNA) has shown potential as a therapeutic option for the treatment of arthritis by silencing specific genes. However, siRNA delivery faces several challenges, including stability, targeting, off-target effects, endosomal escape, immune response activation, intravascular degradation, and renal clearance. A variety of nanotherapeutics like lipidic nanoparticles, liposomes, polymeric nanoparticles, and solid lipid nanoparticles have been developed to improve siRNA cellular uptake, protect it from degradation, and enhance its therapeutic efficacy. Researchers are also investigating chemical modifications and bioconjugation to reduce its immunogenicity. This review discusses the potential of siRNA nanotherapeutics as a therapeutic option for various immune-mediated diseases, including rheumatoid arthritis, osteoarthritis, etc. siRNA nanotherapeutics have shown an upsurge of interest and the future looks promising for such interdisciplinary approach-based modalities that combine the principles of molecular biology, nanotechnology, and formulation sciences.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 5","pages":"Article 100845"},"PeriodicalIF":10.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49721380","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}

引用次数: 1

The enantioselective enhancing effect and mechanistic insights of chiral enhancers in transdermal drug delivery 手性增强剂在经皮给药中的对映选择性增强作用及机理研究

IF 10.2 1区医学

Asian Journal of Pharmaceutical Sciences Pub Date : 2023-09-01 DOI: 10.1016/j.ajps.2023.100849

Yang Zhang , Chao Liu , Dongxiao E. , Wenxuan Jia , Peng Sun , Hui Li , Guojing Yu , Peng Quan , Mingzhe Liu , Liang Fang

{"title":"The enantioselective enhancing effect and mechanistic insights of chiral enhancers in transdermal drug delivery","authors":"Yang Zhang , Chao Liu , Dongxiao E. , Wenxuan Jia , Peng Sun , Hui Li , Guojing Yu , Peng Quan , Mingzhe Liu , Liang Fang","doi":"10.1016/j.ajps.2023.100849","DOIUrl":"https://doi.org/10.1016/j.ajps.2023.100849","url":null,"abstract":"<div><p>Overlook of chiral consideration in transdermal drug delivery increases administrated dose and risk of side effects, decreasing therapeutical effects. To improve the transdermal delivery efficiency of eutomer, this work focused on investigating the law and mechanism of enantioselective enhancing effects of chiral permeation enhancers on drug enantiomers. Chiral nonsteroidal anti-inflammatory drugs and terpene permeation enhancers were selected as model drug and enhancers. The results indicated that the L-isomer of permeation enhancers increased the skin absorption of S-enantiomer of drug and D-isomer improve the permeation of R-enantiomer, in which the enhancement effect (ER) of L-menthol on S-enantiomer (ER = 3.23) was higher than that on R-enantiomer (ER = 1.49). According to the pharmacokinetics results, L-menthol tended to enhance the permeation of S-enantiomer better than R-enantiomer (2.56 fold), and showed excellent <em>in vitro</em>/<em>in vivo</em> correlations. The mechanism study showed that L-isomer of permeation enhancers improved the permeation of S-enantiomer by increasing the retention, but the D-isomer by improving partition for better permeation. Enantioselective mechanism indicated that the weaker chiral H-bond interaction between drug-chiral enhancers was caused by the enantiomeric conformation. Additionally, stronger chiral enhancers-skin interaction between L-isomer and S-conformation of ceramide produced better enhancing effects. In conclusion, enantioselective interaction of chiral drug-chiral enhancers and chiral enhancers-chiral skin played a critical role in transdermal drug delivery, rational utilization of which contributed to improving the uptake of eutomer and inhibiting distomers to decrease a half of dose and side effects, increasing transdermal therapeutical efficiency.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 5","pages":"Article 100849"},"PeriodicalIF":10.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49709891","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}

引用次数: 0

Nanotechnologies meeting natural sources: Engineered lipoproteins for precise brain disease theranostics 纳米技术与自然资源的结合:用于精确脑部疾病治疗的工程脂蛋白。

IF 10.2 1区医学

Asian Journal of Pharmaceutical Sciences Pub Date : 2023-09-01 DOI: 10.1016/j.ajps.2023.100857

Ruoning Wang , Xinru Zhang , Kuanhan Feng , Wei Zeng , Jie Wu , Danni Sun , Ziyi Lu , Hao Feng , Liuqing Di

{"title":"Nanotechnologies meeting natural sources: Engineered lipoproteins for precise brain disease theranostics","authors":"Ruoning Wang , Xinru Zhang , Kuanhan Feng , Wei Zeng , Jie Wu , Danni Sun , Ziyi Lu , Hao Feng , Liuqing Di","doi":"10.1016/j.ajps.2023.100857","DOIUrl":"10.1016/j.ajps.2023.100857","url":null,"abstract":"<div><p>Biological nanotechnologies have provided considerable opportunities in the management of malignancies with delicate design and negligible toxicity, from preventive and diagnostic to therapeutic fields. Lipoproteins, because of their inherent blood-brain barrier permeability and lesion-homing capability, have been identified as promising strategies for high-performance theranostics of brain diseases. However, the application of natural lipoproteins remains limited owing to insufficient accumulation and complex purification processes, which can be critical for individual therapeutics and clinical translation. To address these issues, lipoprotein-inspired nano drug-delivery systems (nano-DDSs), which have been learned from nature, have been fabricated to achieve synergistic drug delivery involving site-specific accumulation and tractable preparation with versatile physicochemical functions. In this review, the barriers in brain disease treatment, advantages of state-of-the-art lipoprotein-inspired nano-DDSs, and bio-interactions of such nano-DDSs are highlighted. Furthermore, the characteristics and advanced applications of natural lipoproteins and tailor-made lipoprotein-inspired nano-DDSs are summarized. Specifically, the key designs and current applications of lipoprotein-inspired nano-DDSs in the field of brain disease therapy are intensively discussed. Finally, the current challenges and future perspectives in the field of lipoprotein-inspired nano-DDSs combined with other vehicles, such as exosomes, cell membranes, and bacteria, are discussed.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 5","pages":"Article 100857"},"PeriodicalIF":10.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10637878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89716794","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}

引用次数: 0

Advances in the development of amorphous solid dispersions: The role of polymeric carriers 非晶固体分散体的研究进展:聚合物载体的作用

IF 10.2 1区医学

Asian Journal of Pharmaceutical Sciences Pub Date : 2023-07-01 DOI: 10.1016/j.ajps.2023.100834

Jie Zhang , Minshan Guo , Minqian Luo , Ting Cai

引用次数: 4

EVs-mediated delivery of CB2 receptor agonist for Alzheimer's disease therapy ev介导的CB2受体激动剂用于阿尔茨海默病治疗

IF 10.2 1区医学

Asian Journal of Pharmaceutical Sciences Pub Date : 2023-07-01 DOI: 10.1016/j.ajps.2023.100835

Yanjing Zhu , Ruiqi Huang , Deheng Wang , Liqun Yu , Yuchen Liu , Runzhi Huang , Shuai Yin , Xiaolie He , Bairu Chen , Zhibo Liu , Liming Cheng , Rongrong Zhu

{"title":"EVs-mediated delivery of CB2 receptor agonist for Alzheimer's disease therapy","authors":"Yanjing Zhu , Ruiqi Huang , Deheng Wang , Liqun Yu , Yuchen Liu , Runzhi Huang , Shuai Yin , Xiaolie He , Bairu Chen , Zhibo Liu , Liming Cheng , Rongrong Zhu","doi":"10.1016/j.ajps.2023.100835","DOIUrl":"10.1016/j.ajps.2023.100835","url":null,"abstract":"<div><p>Alzheimer's disease (AD) is a typical neurodegenerative disease that leads to irreversible neuronal degeneration, and effective treatment remains elusive due to the unclear mechanism. We utilized biocompatible mesenchymal stem cell-derived extracellular vesicles as carriers loaded with the CB2 target medicine AM1241 (EVs-AM1241) to protect against neurodegenerative progression and neuronal function in AD model mice. According to the results, EVs-AM1241 were successfully constructed and exhibited better bioavailability and therapeutic effects than bare AM1241. The Morris water maze (MWM) and fear conditioning tests revealed that the learning and memory of EVs-AM1241-treated model mice were significantly improved. <em>In vivo</em> electrophysiological recording of CA1 neurons indicated enhanced response to an auditory conditioned stimulus following fear learning. Immunostaining and Western blot analysis showed that amyloid plaque deposition and amyloid β (Aβ)-induced neuronal apoptosis were significantly suppressed by EVs-AM1241. Moreover, EVs-AM1241 increased the number of neurons and restored the neuronal cytoskeleton, indicating that they enhanced neuronal regeneration. RNA sequencing revealed that EVs-AM1241 facilitated Aβ phagocytosis, promoted neurogenesis and ultimately improved learning and memory through the calcium-Erk signaling pathway. Our study showed that EVs-AM1241 efficiently reversed neurodegenerative pathology and enhanced neurogenesis in model mice, indicating that they are very promising particles for treating AD.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 4","pages":"Article 100835"},"PeriodicalIF":10.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8d/25/main.PMC10460952.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10176418","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}

引用次数: 2