Asian Journal of Pharmaceutical Sciences最新文献

{"title":"Alkyl chain length-regulated in situ intelligent nano-assemblies with AIE-active photosensitizers for photodynamic cancer therapy","authors":"Lingyi Shen ,&nbsp;Qi-Long Zhang ,&nbsp;Yongchao Yao ,&nbsp;Ya-Li Huang ,&nbsp;Zhichang Zheng ,&nbsp;Ming Li ,&nbsp;Hong Xu ,&nbsp;Lin Tan ,&nbsp;Xukun Liao ,&nbsp;Binyi Xia ,&nbsp;Lin Li ,&nbsp;Carl Redshaw ,&nbsp;Yang Bai ,&nbsp;Chengli Yang","doi":"10.1016/j.ajps.2024.100967","DOIUrl":"10.1016/j.ajps.2024.100967","url":null,"abstract":"<div><div>Photodynamic therapy (PDT) brings new hope for the treatment of breast cancer due to few side effects and highly effective cell killing; however, the low bioavailability of traditional photosensitizers (PSs) and their dependence on oxygen severely limits their application. Aggregation-induced emission (AIE) PSs can dramatically facilitate the photosensitization effect, which can have positive impacts on tumor PDT. To-date, most AIE PSs lack tumor targeting capability and possess poor cell delivery, resulting in their use in large quantities that are harmful to healthy tissues. In this study, a series of AIE PSs based on pyridinium-substituted triphenylamine salts ( TTPAs <strong>1</strong>–<strong>6</strong>) with different alkyl chain lengths are synthesized. Results reveal that TTPAs <strong>1</strong>–<strong>6</strong> promote the generation of type I and II ROS, including ·OH and ¹O₂. In particular, the membrane permeability and targeting of TTPAs <strong>4</strong>-<strong>6</strong> bearing C8-C10 side-chains are higher than TTPAs <strong>1</strong>-<strong>3</strong> bearing shorter alkyl chains. Additionally, they can assemble with albumin, thereby forming nanoparticles (TTPA <strong>4</strong>–<strong>6</strong> NPs) <em>in situ</em> in blood, which significantly facilitates mitochondrial-targeting and strong ROS generation ability. Moreover, the TTPA <strong>4</strong>–<strong>6</strong> NPs are pH-responsive, allowing for increased accumulation or endocytosis of the tumor and enhancing the imaging or therapeutic effect. Therefore, the <em>in vivo</em> distributions of TTPA <strong>4</strong>–<strong>6</strong> NPs are visually enriched in tumor sites and exhibited excellent PDT efficacy. This work demonstrates a novel strategy for AIE PDT and has the potential to play an essential role in clinical applications using nano-delivery systems.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 6","pages":"Article 100967"},"PeriodicalIF":10.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142705969","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}

{"title":"Extracellular vesicles for delivering therapeutic agents in ischemia/reperfusion injury","authors":"Weihang Zhou ,&nbsp;Xinchi Jiang ,&nbsp;Jianqing Gao","doi":"10.1016/j.ajps.2024.100965","DOIUrl":"10.1016/j.ajps.2024.100965","url":null,"abstract":"<div><div>Ischemia/reperfusion (I/R) injury is marked by the restriction and subsequent restoration of blood supply to an organ. This process can exacerbate the initial tissue damage, leading to further disorders, disability, and even death. Extracellular vesicles (EVs) are crucial in cell communication by releasing cargo that regulates the physiological state of recipient cells. The development of EVs presents a novel avenue for delivering therapeutic agents in I/R therapy. The therapeutic potential of EVs derived from stem cells, endothelial cells, and plasma in I/R injury has been actively investigated. Therefore, this review aims to provide an overview of the pathological process of I/R injury and the biophysical properties of EVs. We noted that EVs serve as nontoxic, flexible, and multifunctional carriers for delivering therapeutic agents capable of intervening in I/R injury progression. The therapeutic efficacy of EVs can be enhanced through various engineering strategies. Improving the tropism of EVs <em>via</em> surface modification and modulating their contents via preconditioning are widely investigated in preclinical studies. Finally, we summarize the challenges in the production and delivery of EV-based therapy in I/R injury and discuss how it can advance. This review will encourage further exploration in developing efficient EV-based delivery systems for I/R treatment.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 6","pages":"Article 100965"},"PeriodicalIF":10.7,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268597","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}

{"title":"Insights into microscopic fabrication, macroscopic forms and biomedical applications of alginate composite gel containing metal-organic frameworks","authors":"Yuanke Zhang ,&nbsp;Lvyao Yang ,&nbsp;Min Zhou ,&nbsp;Yanhua Mou ,&nbsp;Dongmei Wang ,&nbsp;Peng Zhang","doi":"10.1016/j.ajps.2024.100952","DOIUrl":"10.1016/j.ajps.2024.100952","url":null,"abstract":"<div><div>Overcoming the poor physicochemical properties of pure alginate gel and the inherent shortcomings of pure metal-organic framework (MOF), alginate/MOF composite gel has captured the interest of many researchers as a tunable platform with high stability, controllable pore structure, and enhanced biological activity. Interestingly, different from the traditional organic or inorganic nanofillers physically trapped or chemically linked within neTtworks, MOFs crystals can not only be dispersed by crosslinking polymerization, but also support self-assembly in-situ under the help of chelating cations with alginate. The latter is influenced by multiple factors and may involve some complex mechanisms of action, which is also a topic discussed deeply in this article while summarizing different preparation routes. Furthermore, various physical and chemical levels of improvement strategies and available macroforms are summarized oriented towards obtaining composite gel with ideal performance. Finally, the application status of this composite system in drug delivery, wound healing and other biomedical fields is further discussed. And the current limitations and future development directions are shed light simultaneously, which may provide guidance for the vigorous development of these composite systems.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 6","pages":"Article 100952"},"PeriodicalIF":10.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142191680","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}

{"title":"Improving treatment for Parkinson's disease: Harnessing photothermal and phagocytosis-driven delivery of levodopa nanocarriers across the blood-brain barrier","authors":"Kaili Liang,&nbsp;Li Yang,&nbsp;Jiawei Kang,&nbsp;Bo Liu,&nbsp;Ding Zhang,&nbsp;Liyan Wang,&nbsp;Wei Wang,&nbsp;Qing Wang","doi":"10.1016/j.ajps.2024.100963","DOIUrl":"10.1016/j.ajps.2024.100963","url":null,"abstract":"<div><div>Parkinson's disease (PD) poses a significant therapeutic challenge, mainly due to the limited ability of drugs to cross the blood-brain barrier (BBB) without undergoing metabolic transformations. Levodopa, a key component of dopamine replacement therapy, effectively enhances dopaminergic activity. However, it encounters obstacles from peripheral decarboxylase, hindering its passage through the BBB. Furthermore, levodopa metabolism generates reactive oxygen species (ROS), exacerbating neuronal damage. Systemic pulsatile dosing further disrupts natural physiological buffering mechanisms. In this investigation, we devised a ROS-responsive levodopa prodrug system capable of releasing the drug and reducing ROS levels in the central nervous system. The prodrug was incorporated within second near-infrared region (NIR-II) gold nanorods (AuNRs) and utilized angiopep-2 (ANG) for targeted delivery across the BBB. The processes of tight junction opening and endocytosis facilitated improved levodopa transport. ROS scavenging helped alleviate neuronal oxidative stress, leading to enhanced behavioral outcomes and reduced oxidative stress levels in a mouse model of PD. Following treatment, the PD mouse model exhibited enhanced flexibility, balance, and spontaneous exploratory activity. This approach successfully alleviated the motor impairments associated with the disease model. Consequently, our strategy, utilizing NIR-II AuNRs and ANG-mediated BBB penetration, coupled with the responsive release of levodopa, offers a promising approach for dopamine supplementation and microenvironmental regulation. This system holds substantial potential as an efficient platform for delivering neuroprotective drugs and advancing PD therapy.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 6","pages":"Article 100963"},"PeriodicalIF":10.7,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142191681","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}

{"title":"A natural compound-empowered podophyllotoxin prodrug nanoassembly magnifies efficacy-toxicity benefits in cancer chemotherapy","authors":"","doi":"10.1016/j.ajps.2024.100892","DOIUrl":"10.1016/j.ajps.2024.100892","url":null,"abstract":"<div><p>Small-molecule prodrug nanoassembly technology with a unique advantage in off-target toxicity reduction has been widely used for antitumor drug delivery. However, prodrug activation remains a rate-limiting step for exerting therapeutic actions, which requires to quickly reach the minimum valid concentrations of free drugs. Fortunately, we find that a natural compound (BL-193) selectively improves the chemotherapy sensitivity of breast cancer cells to podophyllotoxin (PPT) at ineffective dose concentrations. Based on this, we propose to combine prodrug nanoassembly with chemotherapy sensitization to fully unleash the chemotherapeutic potential of PPT. Specifically, a redox-sensitive prodrug (PSSF) of PPT is synthesized by coupling 9-fluorenyl-methanol (Fmoc-OH) with PPT linked via disulfide bond. Intriguingly, PSSF with a π-conjugated structure readily co-assembles with BL-193 into stable nanoassembly. Significantly, BL-193 serves as an excellent chemosensitizer that creates an ultra-low-dose chemotherapeutic window for PPT. Moreover, prodrug design and precise hybrid nanoassembly well manage off-target toxicity. As expected, such a BL-193-empowered prodrug nanoassembly elicits potent antitumor responses. This study offers a novel paradigm to magnify chemotherapy efficacy-toxicity benefits.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 4","pages":"Article 100892"},"PeriodicalIF":10.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000096/pdfft?md5=7511bc92f1d69866729349b4f73ae5d9&pid=1-s2.0-S1818087624000096-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140053929","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}

{"title":"Antibiotic-loaded lactoferrin nanoparticles as a platform for enhanced infection therapy through targeted elimination of intracellular bacteria","authors":"","doi":"10.1016/j.ajps.2024.100926","DOIUrl":"10.1016/j.ajps.2024.100926","url":null,"abstract":"<div><p>Intracellular bacteria can multiply inside host cells and manipulate their biology, and the efficacy of traditional antibiotic drug therapy for intracellular bacteria is limited by inadequate drug accumulation. Fighting against these stealthy bacteria has been a long-standing challenge. Here, a system of stimuli-responsive lactoferrin (Lf) nanoparticles is prepared using protein self-assembly technology to deliver broad-spectrum antibiotic rifampicin (Rif) (Rif@Lf NPs) for enhanced infection therapy through targeted elimination of intracellular bacteria. Compared to Rif@BSA NPs, the Rif@Lf NPs can specifically target macrophages infected by bacteria, thus increasing the accumulation of Rif within macrophages. Subsequently, Rif@Lf NPs with positive surface charge further displayed targeted adherence to the bacteria within macrophages and released Rif rapidly in a redox-responsive manner. Combined with the antibacterial activities of Lf and Rif, the Rif@Lf NPs showed broad-spectrum antibiotic abilities to intracellular bacteria and biofilms. As a result, the Rif@Lf NPs with high safety exhibited excellent therapeutic efficacy in the disease models of subcutaneous infection, sepsis, and bacterial keratitis. Taken together, the antibiotic-loaded Lf nanoparticles present a promising platform to combat pathogen infections through targeted elimination of intracellular bacteria.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 4","pages":"Article 100926"},"PeriodicalIF":10.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000436/pdfft?md5=c2920ac6c91784fdbe34906e4cd292b3&pid=1-s2.0-S1818087624000436-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141026573","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}

{"title":"Design strategies, advances and future perspectives of colon-targeted delivery systems for the treatment of inflammatory bowel disease","authors":"Baoxin Zheng ,&nbsp;Liping Wang ,&nbsp;Yan Yi ,&nbsp;Jun Yin ,&nbsp;Aihua Liang","doi":"10.1016/j.ajps.2024.100943","DOIUrl":"10.1016/j.ajps.2024.100943","url":null,"abstract":"<div><p>Inflammatory bowel diseases (IBD) significantly contribute to high mortality globally and negatively affect patients' qualifications of life. The gastrointestinal tract has unique anatomical characteristics and physiological environment limitations. Moreover, certain natural or synthetic anti-inflammatory drugs are associated with poor targeting, low drug accumulation at the lesion site, and other side effects, hindering them from exerting their therapeutic effects. Colon-targeted drug delivery systems represent attractive alternatives as novel carriers for IBD treatment. This review mainly discusses the treatment status of IBD, obstacles to drug delivery, design strategies of colon-targeted delivery systems, and perspectives on the existing complementary therapies. Moreover, based on recent reports, we summarized the therapeutic mechanism of colon-targeted drug delivery. Finally, we addressed the challenges and future directions to facilitate the exploitation of advanced nanomedicine for IBD therapy.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 4","pages":"Article 100943"},"PeriodicalIF":10.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000606/pdfft?md5=38c03c3dcdb8934d0751b0896ce9b1cb&pid=1-s2.0-S1818087624000606-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141713033","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}

{"title":"Carrier-free cryptotanshinone-peptide conjugates self-assembled nanoparticles: An efficient and low-risk strategy for acne vulgaris","authors":"Quanfu Zeng ,&nbsp;Hongkai Chen ,&nbsp;Zhuxian Wang ,&nbsp;Yinglin Guo ,&nbsp;Yufan Wu ,&nbsp;Yi Hu ,&nbsp;Peiyi Liang ,&nbsp;Zeying Zheng ,&nbsp;Tao Liang ,&nbsp;Dan Zhai ,&nbsp;Yaling Guo ,&nbsp;Li Liu ,&nbsp;Chunyan Shen ,&nbsp;Cuiping Jiang ,&nbsp;Qun Shen ,&nbsp;Yankui Yi ,&nbsp;Qiang Liu","doi":"10.1016/j.ajps.2024.100946","DOIUrl":"10.1016/j.ajps.2024.100946","url":null,"abstract":"<div><p>Acne vulgaris ranks as the second most prevalent dermatological condition worldwide, and there are still insufficient safe and reliable drugs to treat it. Cryptotanshinone (CTS), a bioactive compound derived from traditional Chinese medicine <em>Salvia miltiorrhiza</em>, has shown promise for treating acne vulgaris due to its broad-spectrum antimicrobial and significant anti-inflammatory properties. Nevertheless, its local application is hindered by its low solubility and poor skin permeability. To overcome these challenges, a carrier-free pure drug self-assembled nanosystem is employed, which can specifically modify drug molecules based on the disease type and microenvironment, offering a potential for more effective treatment. We designed and synthesized three distinct structures of cationic CTS-peptide conjugates, creating self-assembled nanoparticles. This study has explored their self-assembly behavior, skin permeation, cellular uptake, and both <em>in vitro</em> and <em>in vivo</em> anti-acne effects. Molecular dynamics simulations revealed these nanoparticles form through intermolecular hydrogen bonding and π-π stacking interactions. Notably, self-assembled nanoparticles demonstrated enhanced bioavailability with higher skin permeation and cellular uptake rates. Furthermore, the nanoparticles exhibited superior anti-acne effects compared to the parent drug, attributed to heightened antimicrobial activity and significant downregulation of the MAPK/NF-κB pathway, leading to reduced expression of pro-inflammatory factors including TNF-α, IL-1β and IL-8. In summary, the carrier-free self-assembled nanoparticles based on CTS-peptide conjugate effectively address the issue of poor skin bioavailability, offering a promising new approach for acne treatment.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 4","pages":"Article 100946"},"PeriodicalIF":10.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000631/pdfft?md5=6301f8c5646035be67edc25666053a17&pid=1-s2.0-S1818087624000631-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141853025","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}

{"title":"From mesenchymal stem cells to their extracellular vesicles: Progress and prospects for asthma therapy","authors":"Shihan Chen ,&nbsp;Jianqing Gao ,&nbsp;Tianyuan Zhang","doi":"10.1016/j.ajps.2024.100942","DOIUrl":"10.1016/j.ajps.2024.100942","url":null,"abstract":"<div><p>Asthma is a widespread public health concern, with an increasing incidence. Despite the implementation of current treatment strategies, asthma control, particularly for severe cases, remains suboptimal. Recent research has revealed the encouraging prospects of extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) as a viable therapeutic option for alleviating asthma symptoms. Therefore, the present review aims to provide an overview of the current progress and the therapeutic mechanisms of using MSC-derived EVs (MSC-EVs) for asthma treatment. Additionally, different administration approaches for EVs and their impacts on biodistribution and the curative outcomes of EVs are summarized. Notably, the potential benefits of nebulized inhalation of MSC-EVs are addressed. Also, the possibilities and challenges of using MSC-EVs for asthma treatment in clinics are highlighted. Overall, this review is intended to give new insight into the utilization of MSC-EVs as a potential biological drug for asthma treatment.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 4","pages":"Article 100942"},"PeriodicalIF":10.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S181808762400059X/pdfft?md5=6dafc5f599cc1f51d447e88d5dffb6bb&pid=1-s2.0-S181808762400059X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141697821","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}

{"title":"Pulmonary fibroblast-specific delivery of siRNA exploiting exosomes-based nanoscaffolds for IPF treatment","authors":"","doi":"10.1016/j.ajps.2024.100929","DOIUrl":"10.1016/j.ajps.2024.100929","url":null,"abstract":"<div><p>Idiopathic pulmonary fibrosis (IPF) is a progressive pulmonary disease that leads to interstitial inflammation, lung damage, and eventually life-threatening complications. Among various pathologic factors, Smad4 is a pivotal molecule involved in the progression and exacerbation of IPF. It mediates nuclear transfer of Smad2/Smad3 complexes and initiates the transcription of fibrosis-promoting genes. Thus, the inhibition of Smad4 expression in pulmonary fibroblasts by small interfering RNAs (siRNAs) might be a promising therapeutic strategy for IPF. Herein, we engineered exosome membranes (EM) by cationic lipid (<em>i.e.</em>, DOTAP) to load siRNAs against Smad4 (DOTAP/siSmad4@EM), and investigated their specific delivery to pulmonary fibroblasts for treating IPF in a mouse model <em>via</em> pulmonary administration. As reference nanoscaffolds, undecorated DOTAP/siSmad4 complexes (lipoplexes, consisting of cationic lipid DOTAP and siRNAs) and siSmad4-loaded lipid nanoparticles (DOTAP/siSmad4@lipo, consisting of lipoplexes fused with DPPC<img>Chol liposomes) were also prepared. The results showed that DOTAP/siSmad4@EM exhibited a higher cellular uptake and gene silencing efficacies in mouse pulmonary fibroblasts (<em>viz.</em>, MLg2908) as compared to the two reference nanoscaffolds. Furthermore, the outcomes of the <em>in vivo</em> experiments illustrated that DOTAP/siSmad4@EM could significantly down-regulate the Smad4 expression with augmented anti-fibrosis efficiency. Additionally, the DOTAP/siSmad4@EM conferred excellent biocompatibility with low cytokine levels in bronchoalveolar lavage fluid and proinflammatory responses in the pulmonary area. Taken together, the outcomes of our investigation imply that specific inhibition of Smad4 expression in pulmonary fibroblasts by pulmonary administrated DOTAP/siSmad4@EM is a promising therapeutic strategy for IPF, which could safely and effectively deliver siRNA drugs to the targeted site of action.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 4","pages":"Article 100929"},"PeriodicalIF":10.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000461/pdfft?md5=c53e6242f3910800eeaba53cccde0449&pid=1-s2.0-S1818087624000461-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141406610","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}