International Journal of Pharmaceutics: X最新文献

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Trastuzumab-functionalized SK-BR-3 cell membrane-wrapped mesoporous silica nanoparticles loaded with pyrotinib for the targeted therapy of HER-2-positive breast cancer 负载有吡罗替尼的曲妥珠单抗功能化 SK-BR-3 细胞膜包裹介孔二氧化硅纳米粒子用于 HER-2 阳性乳腺癌的靶向治疗
IF 5.2 2区 医学
International Journal of Pharmaceutics: X Pub Date : 2024-11-14 DOI: 10.1016/j.ijpx.2024.100302
Xing Liu, Wenwen Shen
{"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,&nbsp;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}
引用次数: 0
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 超声靶向西罗莫司负载微气泡通过抑制 TGF-β1-Smad 信号通路、促进自噬和减轻炎症,改善大鼠心脏移植的急性排斥反应
IF 5.2 2区 医学
International Journal of Pharmaceutics: X Pub Date : 2024-11-04 DOI: 10.1016/j.ijpx.2024.100300
Haiwei Bao, Lulu Dai, Huiyang Wang, Tianan Jiang
{"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,&nbsp;Lulu Dai,&nbsp;Huiyang Wang,&nbsp;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}
引用次数: 0
A hybrid system of mixture models for the prediction of particle size and shape, density, and flowability of pharmaceutical powder blends 用于预测药粉混合物粒度和粒形、密度和流动性的混合模型系统
IF 5.2 2区 医学
International Journal of Pharmaceutics: X Pub Date : 2024-10-28 DOI: 10.1016/j.ijpx.2024.100298
Mohammad Salehian , Jonathan Moores , Jonathan Goldie , Isra' Ibrahim , Carlota Mendez Torrecillas , Ishwari Wale , Faisal Abbas , Natalie Maclean , John Robertson , Alastair Florence , Daniel Markl
{"title":"A hybrid system of mixture models for the prediction of particle size and shape, density, and flowability of pharmaceutical powder blends","authors":"Mohammad Salehian ,&nbsp;Jonathan Moores ,&nbsp;Jonathan Goldie ,&nbsp;Isra' Ibrahim ,&nbsp;Carlota Mendez Torrecillas ,&nbsp;Ishwari Wale ,&nbsp;Faisal Abbas ,&nbsp;Natalie Maclean ,&nbsp;John Robertson ,&nbsp;Alastair Florence ,&nbsp;Daniel Markl","doi":"10.1016/j.ijpx.2024.100298","DOIUrl":"10.1016/j.ijpx.2024.100298","url":null,"abstract":"<div><div>This paper presents a system of hybrid models that combine both mechanistic and data-driven approaches to predict physical powder blend properties from their raw component properties. Mechanistic, probabilistic models were developed to predict the particle size and shape, represented by aspect ratio, distributions of pharmaceutical blends using those of the raw components. Additionally, the accuracy of existing mixture rules for predicting the blend's true density and bulk density was assessed. Two data-driven models were developed to estimate the mixture's tapped density and flowability (represented by the flow function coefficient, FFC) using data from 86 mixtures, which utilized the principal components of predicted particle size and shape distributions in combination with the true density, and bulk density as input data, saving time and material by removing the need for resource-intensive shear testing for raw components. A model-based uncertainty quantification technique was designed to analyse the precision of model-predicted FFCs. The proposed particle size and shape mixture models outperformed the existing approach (weighted average of distribution percentiles) in terms of prediction accuracy while providing insights into the full distribution of the mixture. The presented hybrid system of models accurately predicts the mixture properties of different formulations and components with often <span><math><msup><mi>R</mi><mn>2</mn></msup><mo>&gt;</mo><mn>0.8</mn></math></span>, utilising raw material properties to reduce time and material resources on preparing and characterising blends.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100298"},"PeriodicalIF":5.2,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142658961","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}
引用次数: 0
From design to 3D printing: A proof-of-concept study for multiple unit particle systems (MUPS) printed by dual extrusion fused filament fabrication 从设计到 3D 打印:通过双挤压熔融长丝制造技术打印多单元颗粒系统 (MUPS) 的概念验证研究
IF 5.2 2区 医学
International Journal of Pharmaceutics: X Pub Date : 2024-10-26 DOI: 10.1016/j.ijpx.2024.100299
Lee Roy Oldfield , Aaron Felix Christofer Mentrup , Stefan Klinken-Uth , Tobias Auel , Anne Seidlitz
{"title":"From design to 3D printing: A proof-of-concept study for multiple unit particle systems (MUPS) printed by dual extrusion fused filament fabrication","authors":"Lee Roy Oldfield ,&nbsp;Aaron Felix Christofer Mentrup ,&nbsp;Stefan Klinken-Uth ,&nbsp;Tobias Auel ,&nbsp;Anne Seidlitz","doi":"10.1016/j.ijpx.2024.100299","DOIUrl":"10.1016/j.ijpx.2024.100299","url":null,"abstract":"<div><div>MUPS (multiple unit particle systems) are oral dosage forms consisting of small particles which are filled into capsules or compressed into tablets. Compared to monolithic sustained-release tablets, MUPS tablets rapidly disintegrate inside the stomach releasing the contained small particles, which can be emptied from the stomach independent of housekeeping waves. Control of release can be achieved by adapting the particle composition. Despite the advantages of MUPS, only a limited number of preparations are available on the market. 3D printing could be a new advantageous method to produce MUPS tablets compared to the conventional production via tableting. Due to the increasing research interest in personalised medicine, especially regarding dose adjustments, this flexible production approach could be a promising concept. Therefore, this work proposes a concept for printing MUPS tablets using a dual extrusion fused filament fabrication 3D printer. The general idea is that the two print heads can be used independently to print a water-soluble tablet shell with the first print head and incorporate functional particles into the tablet shell with a second print head using different materials for each step. In this study, a modular four-particle-layered tablet computer model containing 196 cylindrical particles with a diameter of 1.4 mm, a height of 1.0 mm and a total tablet size of 22.6 × 8.5 × 6.0 mm is proposed. A first proof-of-concept study with drug-free commercially available polylactic acid filament for the particles and polyvinyl alcohol filament for the tablet shell revealed critical parameters (such as filament retraction, z-offset and water content of filaments) for the successful printing of the proposed computer model. In addition, the successfully printed model 3D-MUPS tablets and incorporated particles were characterised, revealing a reproducible manufacturing process. The printed model particles had a diameter of 1.27 ± 0.04 mm and a height of 1.05 ± 0.01 mm. One of the challenges of the new approach was to avoid particle agglomeration because of remelting processes during the printing with two print heads. 57.54 ± 18.59 % of the 196 printed particles were present as single particles. Finally, the transferability and suitability with a model API-loaded (paracetamol) hydroxypropyl methylcellulose filament for the particles and a polyvinyl alcohol tablet shell was successfully tested. On average, 80 % of paracetamol was released within 3 h (2–4 h). Overall, this work shows an innovative new manufacturing method for dose-adjustable personalised MUPS tablets but also considers new challenges arising from the different manufacturing processes.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100299"},"PeriodicalIF":5.2,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142571307","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}
引用次数: 0
Augmented glycerosomes as a promising approach against fungal ear infection: Optimization and microbiological, ex vivo and in vivo assessments 增效甘油三酯体是一种很有前景的抗真菌耳部感染的方法:优化及微生物、体内外评估
IF 5.2 2区 医学
International Journal of Pharmaceutics: X Pub Date : 2024-10-22 DOI: 10.1016/j.ijpx.2024.100295
Sadek Ahmed , Heba Attia , Osama Saher , Abdurrahman M. Fahmy
{"title":"Augmented glycerosomes as a promising approach against fungal ear infection: Optimization and microbiological, ex vivo and in vivo assessments","authors":"Sadek Ahmed ,&nbsp;Heba Attia ,&nbsp;Osama Saher ,&nbsp;Abdurrahman M. Fahmy","doi":"10.1016/j.ijpx.2024.100295","DOIUrl":"10.1016/j.ijpx.2024.100295","url":null,"abstract":"<div><div>In the current study, voriconazole (VCZ) augmented glycerosomes were optimized for topical otomycosis management according to a 2<sup>3</sup> factorial design, employing a thin film hydration method. By optimizing Glycerol volume, limonene: VCZ ratio and Span® 60: soybean phosphatidyl choline (PC) ratio, glycerosomes with maximum percentage entrapment efficiency (%EE) and zeta potential (ZP) and minimum vesicle size (VS) and polydispersity index (PDI) were to be obtained. An optimal augmented glycerosomal formula (OAG) that contained 10 mg VCZ, 150 mg PC, and 3 mL glycerol, comprising 2.5: and 0.92:1 ratios of the latter two independent variables, was proposed via numerical optimization. OAG exhibited high %EE and ZP values and acceptable low values for VS and PDI (84.3 ± 2.0 %, −38.8 ± 1.8 mV, 191.0 ± 1.1 nm, and 0.192 ± 0.01, respectively). Extensive in <em>vitro</em> testing of OAG revealed the entrapment of VCZ within OAG, biphasic in <em>vitro</em> release profile, stability for up to 3 months at 2–8 °C and spherical morphology of OAG with VS like that obtained via zetasizer. OAG demonstrated higher permeated amounts of VCZ and flux values than VCZ suspension, leading to an enhancement ratio of 2.56 in the <em>ex vivo</em> permeation study. The deeper penetration ability of OAG demonstrated by Confocal Laser Scanning Microscopy and its superior in <em>vitro</em> antifungal activity confirmed the validity of the <em>ex vivo</em> study. Also, the histopathological study confirmed the safety of OAG for topical use, suggesting that VCZ OAG was a promising topical antimycotic formula.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100295"},"PeriodicalIF":5.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142534423","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}
引用次数: 0
Preservative-free electrospun nanofibrous inserts for sustained delivery of ceftazidime; design, characterization and pharmacokinetic investigation in rabbit's eye 用于头孢他啶持续给药的不含防腐剂的电纺纳米纤维插入物;设计、表征和兔眼药代动力学研究
IF 5.2 2区 医学
International Journal of Pharmaceutics: X Pub Date : 2024-10-22 DOI: 10.1016/j.ijpx.2024.100297
Shiva Taghe , Shahla Mirzaeei
{"title":"Preservative-free electrospun nanofibrous inserts for sustained delivery of ceftazidime; design, characterization and pharmacokinetic investigation in rabbit's eye","authors":"Shiva Taghe ,&nbsp;Shahla Mirzaeei","doi":"10.1016/j.ijpx.2024.100297","DOIUrl":"10.1016/j.ijpx.2024.100297","url":null,"abstract":"<div><div>Ocular drug delivery presents significant challenges, attributed to the various anatomical and physiological barriers, as well as the limitations associated with conventional ocular formulations including low bioavailability, necessitating frequent dosing. The objective of the essay was to design sustained release nanofibrous inserts loaded with ceftazidime (CAZ), an antibiotic effective against gram-negative and gram-positive microorganisms, for the treatment of ocular infections. These nanofibers were fabricated using the electrospinning technique, employing biodegradable polymers such as polyvinyl alcohol (PVA), polycaprolactone (PCL) and Eudragit® (EUD). The nanofibrous inserts exhibited adequate mechanical strength for ocular use with an average diameter &lt; 250 nm. In the initial 12-h period, a burst drug release was observed, followed by a controlled release for 120 h. Cell viability test confirmed the non-toxicity and safety of the nanofibers. The <em>in vivo</em> study demonstrated that the inserts sustain a drug concentration exceeding the minimum inhibitory concentration (MIC) of <em>Pseudomonas aeruginosa</em> and <em>Staphylococcus aureus</em> for 4 and 5 days, respectively. The AUC<sub>0</sub><sub>–</sub><sub>120</sub> for CAZ-PVA-PCL was reported 11,882.81 ± 80.5 μg·h/ml and for CAZ-PVA-EUD was 9649.39 ± 86.84 μg·h/ml. The nanofibrous inserts' extended drug release maintains effective antimicrobial concentrations, avoids the fluctuations of eye drops, and, by being preservative-free, eliminates cytotoxicity.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100297"},"PeriodicalIF":5.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142658483","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}
引用次数: 0
Design of an innovative nanovehicle to enhance brain permeability of a novel 5-HT6 receptor antagonist 设计创新型纳米载体,提高新型 5-HT6 受体拮抗剂的脑渗透性
IF 5.2 2区 医学
International Journal of Pharmaceutics: X Pub Date : 2024-10-21 DOI: 10.1016/j.ijpx.2024.100296
María Javiera Alvarez-Figueroa , Francisco Nuñez-Navarro , Gonzalo Recabarren-Gajardo , José Vicente González-Aramundiz
{"title":"Design of an innovative nanovehicle to enhance brain permeability of a novel 5-HT6 receptor antagonist","authors":"María Javiera Alvarez-Figueroa ,&nbsp;Francisco Nuñez-Navarro ,&nbsp;Gonzalo Recabarren-Gajardo ,&nbsp;José Vicente González-Aramundiz","doi":"10.1016/j.ijpx.2024.100296","DOIUrl":"10.1016/j.ijpx.2024.100296","url":null,"abstract":"<div><div>An innovative nanovehicle based on lipid nanocapsules (LNC) was designed to facilitate the passage of a new 5-HT<sub>6</sub> receptor antagonist, namely PUC-10, through the blood-brain barrier. PUC-10 is a new synthetic <em>N</em>-arylsulfonylindole that has demonstrated potent 5-HT<sub>6</sub> receptor antagonist activity, but it exhibits poor solubility in water, which indicates limited absorption. The lipid nanocapsules designed had a nanometric size (53 nm), a monomodal distribution (PI&lt;0.2), a negative Z potential (−17 ± 7 mV) and allowed efficient PUC-10 encapsulation (74 %). Furthermore, the LNC demonstrated to be stable for at least 4 weeks at 4 °C (storage conditions), for at least 4 h in DMEM at pH 7.4, and for 18 h in water with 5 % DMSO, with both latter conditions maintained at 37 °C. They also demonstrated that cell viability was not affected at the different concentrations studied. Finally, <em>in vitro</em> studies that simulate the blood brain barrier (PAMPA-BBB) demonstrated that the nanoencapsulation of PUC-10 promoted their penetration through the blood-brain barrier, with a calculated permeability of 1.3 × 10<sup>−8</sup> cm/s, compared to the null permeability exhibited by non-nanoencapsulated PUC-10.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100296"},"PeriodicalIF":5.2,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142551881","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}
引用次数: 0
Development of cancer-associated fibroblasts-targeting polymeric nanoparticles loaded with 8-O-methylfusarubin for breast cancer treatment 开发癌症相关成纤维细胞靶向聚合物纳米颗粒,载入 8-O-甲基扶桑黄素用于乳腺癌治疗
IF 5.2 2区 医学
International Journal of Pharmaceutics: X Pub Date : 2024-10-17 DOI: 10.1016/j.ijpx.2024.100294
Kamonlatth Rodponthukwaji , Suyanee Thongchot , Suttikiat Deureh , Tanva Thongkleang , Mattika Thaweesuvannasak , Kornrawee Srichan , Chatchawan Srisawat , Peti Thuwajit , Kytai T. Nguyen , Kwanruthai Tadpetch , Chanitra Thuwajit , Primana Punnakitikashem
{"title":"Development of cancer-associated fibroblasts-targeting polymeric nanoparticles loaded with 8-O-methylfusarubin for breast cancer treatment","authors":"Kamonlatth Rodponthukwaji ,&nbsp;Suyanee Thongchot ,&nbsp;Suttikiat Deureh ,&nbsp;Tanva Thongkleang ,&nbsp;Mattika Thaweesuvannasak ,&nbsp;Kornrawee Srichan ,&nbsp;Chatchawan Srisawat ,&nbsp;Peti Thuwajit ,&nbsp;Kytai T. Nguyen ,&nbsp;Kwanruthai Tadpetch ,&nbsp;Chanitra Thuwajit ,&nbsp;Primana Punnakitikashem","doi":"10.1016/j.ijpx.2024.100294","DOIUrl":"10.1016/j.ijpx.2024.100294","url":null,"abstract":"<div><div>Cancer-associated fibroblasts (CAFs) are abundant stromal cells residing in a tumor microenvironment (TME) which are associated with the progression of tumor. Herein, we developed novel CAFs-targeting polymeric nanoparticles encapsulating a synthetic 8-<em>O</em>-methylfusarubin (OMF) compound (OMF@NPs-anti-FAP). Anti-FAP/fibroblast activation protein antibody was employed as a CAFs-targeting ligand. The physicochemical properties of the synthesized nanomaterials were firstly investigated with various techniques. The cytocompatibility of polymeric nanoparticles (NPs) was elicited through cell viability of CAFs and human breast epithelial cells, MCF-10A. Additionally, the anti-FAP-conjugated NPs displayed different degrees of cellular internalization regarding the FAP expression level on the CAFs' surface. However, CAFs exposed to NPs containing OMF demonstrated significant cell death which were associated with the apoptotic pathway as confirmed by caspase-3/7 activity. Upon OMF@NPs-anti-FAP treatment, an enhanced toxicity was clearly observed in 3D spheroid models. High FAP-expressed PC-B-132CAFs demonstrated a high percentage of cell death compared to other cells with a low level of FAP expression analyzed by flow cytometry (e.g. MCF-10A, HDFa, and PC-B-142CAFs). This result emphasized the importance of anti-FAP antibody as a targeting ligand. These findings suggest that the fabricated nanosystem of OMF-loaded polymeric NPs with CAFs' high specificity holds a potential NP-based platform for improvement in breast cancer treatment.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100294"},"PeriodicalIF":5.2,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142534422","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}
引用次数: 0
Effect of wound dressing porosity and exudate viscosity on the exudate absorption: In vitro and in silico tests with 3D printed hydrogels 伤口敷料孔隙率和渗出物粘度对渗出物吸收的影响:三维打印水凝胶的体外和体内测试
IF 5.2 2区 医学
International Journal of Pharmaceutics: X Pub Date : 2024-10-16 DOI: 10.1016/j.ijpx.2024.100288
Alejandro Seijo-Rabina , Santiago Paramés-Estevez , Angel Concheiro , Alberto Pérez-Muñuzuri , Carmen Alvarez-Lorenzo
{"title":"Effect of wound dressing porosity and exudate viscosity on the exudate absorption: In vitro and in silico tests with 3D printed hydrogels","authors":"Alejandro Seijo-Rabina ,&nbsp;Santiago Paramés-Estevez ,&nbsp;Angel Concheiro ,&nbsp;Alberto Pérez-Muñuzuri ,&nbsp;Carmen Alvarez-Lorenzo","doi":"10.1016/j.ijpx.2024.100288","DOIUrl":"10.1016/j.ijpx.2024.100288","url":null,"abstract":"<div><div>Exudate absorption is a key parameter for proper wound dressing performance. Unlike standardized tests that consider exudate viscosity close to that of water, patients' exudates vary greatly in composition and, therefore, viscosity. This work aimed to investigate the effects of exudate viscosity and pore size of hydrogel-like dressings on the exudate absorption rate to establish rational criteria for the design of dressings that can meet the personalized needs of wound treatment. Computer-aided design (CAD) was used for Digital Light Processing (DLP) 3D printing of hydrogels with 0%, 30% and 60% porosity. The hydrogels were characterized in detail, and the absorption of two simulated exudate fluids (SEFs) was video-recorded. The same CAD files were used to develop <em>in silico</em> models to simulate exudate uptake rate. Both <em>in vitro</em> data and <em>in silico</em> modeling revealed that low-viscosity SEF penetrates faster through relatively small hydrogel pores (approx. 400 μm) compared to larger pores (approx. 1100 μm) due to capillary forces. However, <em>in vitro</em> vertical uptake took longer than when simulated using CAD design due to lateral fluid absorption through the pore walls in the hydrogel bulk. Distortions of hydrogel channels (micro-CT images) and lateral fluid absorption should be both considered for <em>in silico</em> simulation of SEF penetration. Overall, the results evidenced that porous hydrogel dressings allow rapid penetration (within a few seconds) and hosting of exudates, especially for pore size &lt;1 mm. This information may be useful for design criteria of wound dressings with adequate fluid handling and drug release rate.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100288"},"PeriodicalIF":5.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142444682","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}
引用次数: 0
Ocular mucoadhesive and biodegradable spanlastics loaded cationic spongy insert for enhancing and sustaining the anti-inflammatory effect of prednisolone Na phosphate; Preparation, I-optimal optimization, and In-vivo evaluation 用于增强和维持泼尼松龙磷酸钠抗炎效果的眼部粘液粘附性和可生物降解的含阳离子海绵插件;制备、I-优化和体内评估
IF 5.2 2区 医学
International Journal of Pharmaceutics: X Pub Date : 2024-10-16 DOI: 10.1016/j.ijpx.2024.100293
Mayada Said , Khaled M. Ali , Munerah M. Alfadhel , Obaid Afzal , Basmah Nasser Aldosari , Maha Alsunbul , Rawan Bafail , Randa Mohammed Zaki
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