{"title":"Optimizing extrusion processes and understanding conformational changes in itraconazole amorphous solid dispersions using in-line UV–Vis spectroscopy and QbD principles","authors":"Hetvi Triboandas , Mariana Bezerra , Juan Almeida , Matheus de Castro , Bianca Aloise Maneira Corrêa Santos , Walkiria Schlindwein","doi":"10.1016/j.ijpx.2024.100308","DOIUrl":"10.1016/j.ijpx.2024.100308","url":null,"abstract":"<div><div>This paper presents a comprehensive investigation of the manufacturing of itraconazole (ITZ) amorphous solid dispersions (ASDs) with Kolllidon® VA64 (KVA64) using hot-melt extrusion (HME) and in-line process monitoring, employing a Quality by Design (QbD) approach. A sequential Design of Experiments (DoE) strategy was utilized to optimize the manufacturing process, with in-line UV–Vis spectroscopy providing real-time monitoring. The first DoE used a fractional factorial screening design to evaluate critical process parameters (CPPs), revealing that ITZ concentration had the most significant impact on the product quality attributes. The second DoE, employing a central composite design, explored the interactions between feed rate and screw speed, using torque and absorbance at 370 nm as responses to develop a design space. Validation studies confirmed process robustness across multiple days, with stable in-line UV–Vis spectra and consistent product quality using 30 % ITZ, 300 rpm, 150 °C and 7 g/min as the optimized process conditions. Theoretical and experimental analyses indicated that shifts in UV–Vis spectra at different ITZ concentrations were due to conformational changes in ITZ, which were confirmed through density functional theory (DFT) calculations and infrared spectroscopy. This work offers novel insights into the production and monitoring of ITZ-KVA64-ASDs, demonstrating that in-line UV–Vis spectroscopy is a powerful tool for real-time process monitoring and/or control.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100308"},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alanood S. Alfutaimani , Nouf K. Alharbi , Amirah S. Alahmari , Almaha A. Alqabbani , Abdulaziz M. Aldayel
{"title":"Exploring the landscape of Lipid Nanoparticles (LNPs): A comprehensive review of LNPs types and biological sources of lipids","authors":"Alanood S. Alfutaimani , Nouf K. Alharbi , Amirah S. Alahmari , Almaha A. Alqabbani , Abdulaziz M. Aldayel","doi":"10.1016/j.ijpx.2024.100305","DOIUrl":"10.1016/j.ijpx.2024.100305","url":null,"abstract":"<div><div>Lipid nanoparticles (LNPs) have emerged as promising carriers for delivering therapeutic agents, including mRNA-based immunotherapies, in various biomedical applications. The use of LNPs allows for efficient delivery of drugs, resulting in enhanced targeted delivery to specific tissues or cells. These LNPs can be categorized into several types, including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, and lipid-polymer hybrid nanoparticles. The preparation of LNPs involves the manipulation of their structural, dimensional, compositional, and physical characteristics via the use of different methods in the industry. Lipids used to construct LNPs can also be derived from various biological sources, such as natural lipids extracted from plants, animals, or microorganisms. This review dives into the different types of LNPs and their preparation methods. More importantly, it discusses all possible biological sources that are known to supply lipids for the creation of LNPs. Natural lipid reservoirs have surfaced as promising sources for generating LNPs. The use of LNPs in drug delivery is expected to increase significantly in the coming years. Herein, we suggest some environmentally friendly and biocompatible sources that can produce lipids for future LNPs production.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100305"},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Faezeh Dangkoub, Mehri Bemani Naeini, Shima Akar, Ali Badiee, Mahmoud Reza Jaafari, Mojtaba Sankian, Mohsen Tafaghodi, Seyed Ali Mousavi Shaegh
{"title":"Preparation of atorvastatin calcium-loaded liposomes using thin-film hydration and coaxial micromixing methods: A comparative study.","authors":"Faezeh Dangkoub, Mehri Bemani Naeini, Shima Akar, Ali Badiee, Mahmoud Reza Jaafari, Mojtaba Sankian, Mohsen Tafaghodi, Seyed Ali Mousavi Shaegh","doi":"10.1016/j.ijpx.2024.100309","DOIUrl":"https://doi.org/10.1016/j.ijpx.2024.100309","url":null,"abstract":"<p><p>Development of techniques to produce nanoformulations in a controlled and reproducible manner is of great importance for research, clinical trials, and industrial scale-up. This research aimed to introduce a cost-effective micromixing approach for the nanoassembly of liposomes and compared with thin-film hydration (TFH) method. Numerical simulations and design of experiments (DOE) by response surface methodology (RSM) were used to evaluate the effects of input parameters on liposome properties, aiming to identify optimal conditions. Anionic liposomes without or with atorvastatin calcium (ATC) produced using TFH and the micromixing methods showed similar characteristics in size (150-190 nm), PDI (<0.2), and zeta potential (-50 to -60 mV). Both methods achieved about 70 % encapsulation efficiency with similar drug release profile for ATC-containing liposomes. Analysis of stability and DSC thermograms revealed comparable outcomes for liposomes prepared using both techniques. Nanoliposomes produced via both approaches indicated similar in vitro biological performance regarding cellular uptake and cell viability. The micromixing approach presented an alternative method to produce nanoliposomes in a one-step manner with high controllability and reproducibility without requiring specialized equipment. Compatibility of the micromixer with various solvents, including those detrimental to conventional microfluidic materials like PDMS and thermoplastics, enables exploration of a wide range of formulations.</p>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"100309"},"PeriodicalIF":5.2,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11653151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Di Huang , Yinsha Yao , Yifei Lou , Longfa Kou , Qing Yao , Ruijie Chen
{"title":"Disulfiram and cancer immunotherapy: Advanced nano-delivery systems and potential therapeutic strategies","authors":"Di Huang , Yinsha Yao , Yifei Lou , Longfa Kou , Qing Yao , Ruijie Chen","doi":"10.1016/j.ijpx.2024.100307","DOIUrl":"10.1016/j.ijpx.2024.100307","url":null,"abstract":"<div><div>The initial focus of the clinical application of disulfiram was its efficacy in treating alcoholism. However, recent research has revealed its potential as an anti-tumor agent and even as an enhancer of cancer immunotherapy. Disulfiram has received safety approval from the FDA, indicating its safety advantages over other substances used for disease treatment. Although clinical trials have been conducted on strategies involving disulfiram or its combination with other anti-tumor drugs, the treatment outcomes have not yielded satisfactory results, thereby emphasizing the significance of addressing drug delivery as a crucial challenge to be resolved. The need to explore advanced nano-delivery systems and the potential immunotherapy enhancement effect of disulfiram in cancer treatment has increased. This review highlights various ways in which disulfiram can combat cancer and importantly, activate immune-related mechanisms. It also discusses obstacles related to delivering disulfiram and provides existing solutions in terms of drug delivery. These drug delivery strategies offer solutions to address various challenges encountered in diverse delivery methods and aim to achieve enhanced therapeutic effects. The focus is on recent advancements in disulfiram delivery strategies and the future potential of disulfiram in immune regulation.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100307"},"PeriodicalIF":5.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prodigiosin hydrogel to promote healing of trauma-infected multidrug-resistant Staphylococcus aureus mice wounds","authors":"Xin Wang, Guangfan Meng, Zongyu Zhang, Jiacheng Zhao, Shaoyu Wang, Dongliang Hua, JingZhang, Jie Zhang","doi":"10.1016/j.ijpx.2024.100306","DOIUrl":"10.1016/j.ijpx.2024.100306","url":null,"abstract":"<div><div>Wound infections caused by Multidrug-resistant <em>Staphylococcus aureus</em> (MRSA) have been regarded as a challenging problem in clinic for the long time. In this study, based on the excellent antimicrobial effect of prodigiosin(PG) and the ability of hydrogel dressing in terms of tissue repair and regeneration, we prepared the PG hydrogel as a treatment for the wound infection induced by MRSA. Rheological tests indicated that PG hydrogel as a semi-solid gel had good mechanical properties. In ex vitro drug permeation studies and dermatokinetic studies showed that PG hydrogel had high PG permeability and were capable of short-term retention in the skin. In addition, in vivo experiments for mouse skin wounds showed that the serum levels of inflammatory factors including IL-β and other inflammatory factors were reduced, the inflammatory infiltration of tissues was reduced, the transcript levels of genes such as COL1A1 were up-regulated at different stages of wound healing, and the relative abundance of genera such as <em>Desulfovibrio</em> was lowered after treatment with PG hydrogel, which facilitated wound healing in mice. Our study would provide a new solution to the clinical shortage of drugs for the treatment of MRSA infection and provide a research basis for improving the comprehensive values of PG.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100306"},"PeriodicalIF":5.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Trastuzumab-functionalized SK-BR-3 cell membrane-wrapped mesoporous silica nanoparticles loaded with pyrotinib for the targeted therapy of HER-2-positive breast cancer","authors":"Xing Liu, Wenwen Shen","doi":"10.1016/j.ijpx.2024.100302","DOIUrl":"10.1016/j.ijpx.2024.100302","url":null,"abstract":"<div><div>In this study, the trastuzumab-functionalized SK-BR-3 cell membrane-wrapped mesoporous silica nanoparticles loaded with pyrotinib (Tra-CM-MSN-PYR) were prepared for targeted therapy of HER2-positive breast cancer. Transmission electron microscopy (TEM) characterization showed that MSN had a spherical morphology with mesoporous channels and that the structure of Tra-CM-MSN was a cell membrane (CM) layer successfully coated on the surface of MSN. A cellular uptake assay demonstrated that FITC-labeled Tra-CM-MSN were taken up by SK-BR-3 breast cancer cells, which illustrated that Tra-CM-MSN had good targeting ability compared with CM-MSN and MSN. In vivo imaging experiments demonstrated significant accumulation of FITC-labeled Tra-CM-MSN in tumor tissues, further proving that Tra-CM-MSN have superior targeting properties. Cell apoptosis experiments suggested that Tra-CM-MSN-PYR significantly inhibited the proliferation of SK-BR-3 breast cancer cells. The results of in vivo animal experiments also showed that Tra-CM-MSN-PYR significantly inhibited tumor growth. These results indicate that Tra-CM-MSN-PYR has potential application as a targeted therapy for HER2-positive breast cancer in the future.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100302"},"PeriodicalIF":5.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142658487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Martin Lück, Stefan Klinken-Uth, Peter Kleinebudde
{"title":"Kinetics of elastic recovery in roll compaction","authors":"Martin Lück, Stefan Klinken-Uth, Peter Kleinebudde","doi":"10.1016/j.ijpx.2024.100303","DOIUrl":"10.1016/j.ijpx.2024.100303","url":null,"abstract":"<div><div>Elastic recovery (<span><math><mi>ER</mi></math></span>) has been investigated and discussed extensively in the field of tableting. However, until now only limited data is available regarding <span><math><mi>ER</mi></math></span> in roll compaction. Therefore, a previously established in-line measurement technique was rolled out to further investigate the kinetics of <span><math><mi>ER</mi></math></span> in roll compaction and the effects of specific compaction force (<span><math><mi>SCF</mi></math></span>) and roll speed (<span><math><mi>RS</mi></math></span>). In-line laser triangulation measurements at different positions within a roll rotation as well as measurement over time after the process has been stopped were utilized. Pure microcrystalline cellulose (<span><math><mi>MCC</mi></math></span>) and two placebo powder blend formulations were analysed. Successful fit of the contained <span><math><mi>ER</mi></math></span> profiles emphasized that the <span><math><mi>ER</mi></math></span> on the roll surface is build out of two exponential kinetics. Starting with a dominating fast <span><math><mi>ER</mi></math></span> (<span><math><msub><mi>ER</mi><mi>A</mi></msub></math></span>), characterized by a high increase of the ribbon thickness after passing the gap width, followed by a slower <span><math><mi>ER</mi></math></span> (<span><math><msub><mi>ER</mi><mi>B</mi></msub></math></span>). Sigma minus plot analysis showed that increasing <span><math><mi>RS</mi></math></span> led to an accelerated <span><math><msub><mi>ER</mi><mi>A</mi></msub></math></span> and <span><math><msub><mi>ER</mi><mi>B</mi></msub></math></span> which was related to the viscoelastic behaviour of <span><math><mi>MCC</mi></math></span>. The <span><math><mi>SCF</mi></math></span> only had an effect on the kinetics of <span><math><mi>ER</mi></math></span> if a brittle filler was added to the mixture. The conducted study established the first approach in literature to characterize the kinetics of <span><math><mi>ER</mi></math></span> in roll compaction. It supports the understanding and characterization of relaxation times and the effect of the <span><math><mi>RS</mi></math></span> and <span><math><mi>SCF</mi></math></span> in roll compaction.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100303"},"PeriodicalIF":5.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142701186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Afzal Hussain , Mohammad A. Altamimi , Musaad A. Alshammari
{"title":"Mechanistic insights of desmopressin loaded elastic liposomes for transdermal delivery: HSPiP predictive parameters and instrumental based evidences","authors":"Afzal Hussain , Mohammad A. Altamimi , Musaad A. Alshammari","doi":"10.1016/j.ijpx.2024.100304","DOIUrl":"10.1016/j.ijpx.2024.100304","url":null,"abstract":"<div><div>Desmopressin acetate (DA) is a first-line option for the treatment of hemophilia A, von Willebrand's disease, nocturnal enuresis, central diabetes insipidus, and various traumatic injuries. We extended previously reported desmopressin-loaded elastic liposomes (ODEL1) to investigate mechanistic insights into ODEL1 mediated augmented permeation across rat skin. HSPiP software and instrumental techniques such as differential scanning calorimeter (DSC), Fourier Transform infrared (FTIR), scanning electron microscopy (SEM), and fluorescent microscopy provided better understandings of permeation behavior. HSPiP was used to compare Hansen solubility parameter (HSP) of ODEL1, DA, components, and rat skins (control and treated) in terms of dispersion forces (δ<sub>d</sub>), polar forces (δ<sub>p</sub>), and hydrogen bonding (δ<sub>h</sub>). FTIR, DSC, fluorescence microscopy, and SEM provided a detailed mechanistic understanding of the changes occurred after treatment. The values of δ<sub>d</sub>, δ<sub>p</sub>, and δ<sub>H</sub> for DA were 20.6, 31.9, and 18.2 MPa<sup>1/2</sup>, respectively, whereas these were 15.6, 14.97, and 2.4 MPa<sup>1/2</sup> for ODEL1, respectively, suggesting remarkable permeation of DA by changing innate cohesive energies of the skin. DA primarily interacts through δ<sub>d</sub> and δ<sub>p</sub> with the ODEL1 and the skin. Furthermore, the stretching and bending vibrations (molecular interactions) of the treated skins were quite diverse as compared to the untreated skin. ODEL1 caused a substantial thermal changes (shifted 67 to 65 °C, and 79 to 82.5 °C) for the surface protein and glycoprotein as compared to the untreated skin. Fluorescence and SEM confirmed relatively intense surface perturbation of the treated skin as compared to the control. Thus, ODEL1 was efficient in interacting with the skin surface for reversible changes and subsequently resulted in high permeation and drug deposition.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100304"},"PeriodicalIF":5.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142701187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marco Ruggeri , Fabrizio De Luca , Amedeo Ungolo , Barbara Vigani , Alejandro J. Paredes , Eleonora Russo , Maria Grazia Bottone , Eleonora Bianchi , Franca Ferrari , Silvia Rossi , Giuseppina Sandri
{"title":"Olive mill wastewater: From by-product to smart antioxidant material","authors":"Marco Ruggeri , Fabrizio De Luca , Amedeo Ungolo , Barbara Vigani , Alejandro J. Paredes , Eleonora Russo , Maria Grazia Bottone , Eleonora Bianchi , Franca Ferrari , Silvia Rossi , Giuseppina Sandri","doi":"10.1016/j.ijpx.2024.100301","DOIUrl":"10.1016/j.ijpx.2024.100301","url":null,"abstract":"<div><div>Olive mill wastewater (OMWW) is a byproduct of olive oil extraction that represents a critical environmental concern due to its potential adverse effects on ecosystems. Given these premises, spray-dried microparticles were designed and developed using maltodextrins as carriers to encapsulate OMWW bioactive compounds. The microparticles were manufactured using an easily scalable and sustainable spray-drying process. The resulting microparticles were smooth, spherical, and exhibited a mean particle size of about 18 μm. The systems demonstrated notable antioxidant properties with a DPPH radical scavenging activity higher than 60 %, due to the polyphenolic compounds of OMWW (about 24 g gallic acid equivalents per g of sample). In addition, the microparticles supported fibroblast and macrophage viability at concentrations up to 1 mg/mL. They also determined a 4-fold inflammation reduction in macrophages, improved collagen expression in fibroblasts, and modulated oxidative stress on aged fibroblasts. In conclusion, these microparticles could be considered as promising medical devices in wound healing, while offering a sustainable solution for valorizing OMWW.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100301"},"PeriodicalIF":5.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142701185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ultrasound-targeted sirolimus-loaded microbubbles improves acute rejection of heart transplantation in rats by inhibiting TGF-β1-Smad signaling pathway, promoting autophagy and reducing inflammation","authors":"Haiwei Bao, Lulu Dai, Huiyang Wang, Tianan Jiang","doi":"10.1016/j.ijpx.2024.100300","DOIUrl":"10.1016/j.ijpx.2024.100300","url":null,"abstract":"<div><div>Acute rejection (AR) remains a pivotal complication and leading cause of mortality within the first year following heart transplantation (HT). In this study, we assessed the impact of ultrasound-targeted microbubbles loaded with sirolimus (SIR-MBs) on AR in a rat HT model and delved into the underlying mechanisms. We established a rat abdominal ectopic HT model, which was stratified into three groups receiveing the PBS, SIR-MBs + ultrasound-targeted microbubble destruction (UTMD), and sirolimus, respectively. The protective effects of each treatments on survival rate, inflammatory response, autophagy and TGF-β1-Smad signaling pathway-related proteins were evaluted. Additionally, rescue experiment was performed <em>via</em> adding the autophagy inhibitor or TGF-β1 agonist in combination therapy. UTMD combined SIR-MBs mediated 15-fold higher local drug concentration compared to direct sirolimus administration. The infiltration of inflammatory cells in the transplanted hearts indicated that SIR-MBs combined with UTMD were effective in mitigating the inflammatory response, achieving levels significantly lower than those observed in the sirolimus group. Furthermore, after SIR-MBs combined with UTMD treatment, the expression levels of TGF-β1-Smad signaling pathway-related proteins in heart tissues also showed a significant decrease compared to the model control group. Conversely, the expressions of autophagy proteins LC3-II, Beclin-1 and β-arrestin showed an up-regulated trend. Rescue experiments also revealed that the enhancement in survival trends was markedly suppressed following the administration of CsA or SRI-011381, respectively. Collectively, our findings suggest that SIR-MBs combined with UTMD augment the local treatment efficacy for AR in rat HT models by inhibiting the TGF-β1-Smad signaling pathway, promoting autophagy, and alleviating inflammation.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100300"},"PeriodicalIF":5.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142658488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}