International Journal of Pharmaceutics: X最新文献

An aptamer-conjugated mesoporous polydopamine formulation for synergistic targeted and photothermal therapy of hepatocellular carcinoma 一种用于肝细胞癌靶向和光热协同治疗的适配体共轭介孔聚多巴胺制剂

IF 5.2 2区医学

International Journal of Pharmaceutics: X Pub Date : 2025-04-24 DOI: 10.1016/j.ijpx.2025.100335

Yue Yang , Chonggao Wang , Shiwei Liu , Yewei Zhang

{"title":"An aptamer-conjugated mesoporous polydopamine formulation for synergistic targeted and photothermal therapy of hepatocellular carcinoma","authors":"Yue Yang , Chonggao Wang , Shiwei Liu , Yewei Zhang","doi":"10.1016/j.ijpx.2025.100335","DOIUrl":"10.1016/j.ijpx.2025.100335","url":null,"abstract":"<div><div>This study aimed to create multifunctional nanoparticles (NPs), specifically [email protected] (AMLC), for the purpose of developing effective strategies for treating hepatocellular carcinoma (HCC) through targeted therapy and photothermal therapy (PTT). The study involved synthesizing mesoporous polydopamine (MPDA)-NPs, loading lenvatinib (Len) and Cy5.5 via incubation, and modifying AS1411 aptamer onto MPDA via a covalent chemical reaction. The NPs were characterized using techniques such as ultra-micro spectrophotometry, Fourier transform infrared spectroscopy, and transmission electron microscopy. Target-specific uptake and cell-killing assays were utilized to evaluate AMLC-mediated synergistic therapy while using Western blotting and immunofluorescence to confirm the underlying mechanism. Consequently, the nanoparticles (NPs) were successfully synthesized, demonstrating excellent solvent solubility and stability, with controlled drug release achieved in acidic environments (maximum release efficiency≈80 %). In vitro and in vivo studies revealed that these NPs could more effectively target hepatocellular carcinoma (HCC) cells, enhancing the targeting capability of lenvatinib. Under near-infrared (NIR) laser irradiation, the targeted photothermal therapy (PTT) exhibited significantly improved anticancer efficacy, with AMCL+PTT treatment resulting in up to 76 % tumor volume reduction‌ (<em>P</em> < 0.01). The study demonstrates that AMLC, a multifunctional nano-delivery system, significantly enhances Lenvatinib's tumor-targeting capacity while exhibiting excellent biocompatibility. Combined with photothermal therapy (PTT), it demonstrates potent antitumor efficacy, showing promising clinical translation potential for hepatocellular carcinoma (HCC) therapy.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100335"},"PeriodicalIF":5.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Ultra-sensitive pH responsive hydrogels with injectable and self-healing performance for controlled drug delivery 超敏感的pH反应水凝胶，具有可注射和自愈性能，用于控制药物输送

IF 5.2 2区医学

International Journal of Pharmaceutics: X Pub Date : 2025-04-15 DOI: 10.1016/j.ijpx.2025.100334

Yang Yu , Yili Zhao , Yujiao Zou , Chanyi Lu , Ni Li , Zhiyuan Shi , Xin Li , Xixi Lai

{"title":"Ultra-sensitive pH responsive hydrogels with injectable and self-healing performance for controlled drug delivery","authors":"Yang Yu , Yili Zhao , Yujiao Zou , Chanyi Lu , Ni Li , Zhiyuan Shi , Xin Li , Xixi Lai","doi":"10.1016/j.ijpx.2025.100334","DOIUrl":"10.1016/j.ijpx.2025.100334","url":null,"abstract":"<div><div>Ultra-sensitive pH-responsive drug delivery system designed to operate within the slightly acidic microenvironment of tumors are highly desired for hydrogel applications in cancer therapy. In this study, 4-Formylbenzoic acid modified polyvinyl alcohol (PVA-FBA, PF) was synthesized and utilized as a carrier for encapsulating the anticancer drug Doxorubicin (Dox). This was subsequently crosslinked with polyethylenimine (PEI) via benzoic-imine bond to form drug-loaded PVA-FBA/PEI hydrogel (D-PFP). The D-PFP hydrogel was characterized using various techniques. The results indicated that the optimal conditions for hydrogel preparation involved using PF-0.25 polymer, which had an aldehyde group content of 0.82 mmol/g, as the precursor, along with a 12 wt% precursor solution for crosslinking with a 5 wt% PEI solution. The resulting hydrogel exhibited good structural stability and favorable morphology. Drug release studies indicated that the hydrogel demonstrated minimal drug leakage under physiological conditions (pH 7.4), while exhibiting a significantly higher drug release rate at pH 6.8, thereby underscoring its superior pH sensitivity. Rheological evaluations further confirmed its injectability and self-healing properties. Moreover, the hydrogel displayed excellent cytocompatibility and significantly inhibited cancer cell activity at pH 6.8. These characteristics suggest the potential of this hydrogel as a drug delivery system with ultra-sensitive drug release properties, particularly for future applications in chemotherapy for cancer.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100334"},"PeriodicalIF":5.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Terconazole loaded edge-activated hybrid elastosome for revamped corneal permeation in ocular mycosis: In-vitro characterization, statistical optimization, microbiological assessment, and in-vivo evaluation. Terconazole负载边缘活化杂交弹性体用于改善眼真菌病的角膜渗透：体外表征，统计优化，微生物学评估和体内评估。

IF 5.2 2区医学

International Journal of Pharmaceutics: X Pub Date : 2025-04-08 DOI: 10.1016/j.ijpx.2025.100333

Sadek Ahmed , Michael M. Farag , Heba Attia , Bander Balkhi , Islam M. Adel , Asmaa Ashraf Nemr

{"title":"Terconazole loaded edge-activated hybrid elastosome for revamped corneal permeation in ocular mycosis: In-vitro characterization, statistical optimization, microbiological assessment, and in-vivo evaluation.","authors":"Sadek Ahmed , Michael M. Farag , Heba Attia , Bander Balkhi , Islam M. Adel , Asmaa Ashraf Nemr","doi":"10.1016/j.ijpx.2025.100333","DOIUrl":"10.1016/j.ijpx.2025.100333","url":null,"abstract":"<div><div>Herein, we investigated the preparation and characterization of Terconazole loaded edge-activated hybrid elastosome (TCN-EHE) adopting thin film hydration technique for the treatment of ocular mycosis. Terconazole (TCN) is a broad spectrum antimycotic agent suffering from sparse aqueous solubility impeding its use in ophthalmic preparations. The scrutinized formulation variables namely X<sub>1</sub>: Surfactant: Edge activator ratio (SAA: EA), X<sub>2</sub>: Pluronic® L121 contribution (% of total SAA) and X<sub>3</sub>: EA concentration (%<em>w</em>/<em>v</em>) were optimized adopting D-optimal design. Ten runs were prepared and characterized regarding their entrapment efficiency, particle size, polydispersity index and zeta potential. An optimized formula was generated, with high desirability, exhibited satisfactory entrapment efficiency, nanoscaled particle size aligning with TEM, plausible zeta potential and bi-phasic release pattern which were not altered after short-term storage. The optimized TCN-EHE displayed 1.94-fold enhanced ex-vivo corneal permeation flux. Safety was ratified through measured corneal hydration level, pH and histopathological evaluation. In-vivo corneal uptake visualized by confocal laser microscopy demonstrated 2.7-fold deeper penetration. Moreover, Superior antifungal activity has been demonstrated displaying 37 % bigger zone of inhibition, 8-fold lower minimum inhibitory and minimum fungal concentration alongside significantly higher biofilm inhibition activity at all tested concentrations for the optimized TCN-EHE compared to TCN suspension. Conclusively, we could prospect that TCN-EHE might be a revamped therapeutic alternative for the delivery of poorly soluble antimycotic agents for the combat of ocular mycosis.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100333"},"PeriodicalIF":5.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Does tablet shape and height influence survival of fluidized bed-granulated living microorganisms during compaction? 压实过程中，片剂的形状和高度是否影响流化床颗粒化活微生物的存活？

IF 5.2 2区医学

International Journal of Pharmaceutics: X Pub Date : 2025-04-05 DOI: 10.1016/j.ijpx.2025.100332

Karl Vorländer , Lukas Bahlmann , Arno Kwade , Jan Henrik Finke , Ingo Kampen

{"title":"Does tablet shape and height influence survival of fluidized bed-granulated living microorganisms during compaction?","authors":"Karl Vorländer , Lukas Bahlmann , Arno Kwade , Jan Henrik Finke , Ingo Kampen","doi":"10.1016/j.ijpx.2025.100332","DOIUrl":"10.1016/j.ijpx.2025.100332","url":null,"abstract":"<div><div>The provision of effective probiotic formulations requires gentle processing to maintain the viability of the probiotic microorganisms, which is essential for their health-promoting effects. The drying of microorganisms by fluidized bed spray granulation and subsequent processing of the granules into tablets has proven to be a promising process route in previous studies of the same authors. In these, the influence of various factors was considered using cylindrical tablets with a diameter of 11.28 mm and a mass of 450 mg. These flat tablets are unpleasant to ingest and other tablet geometries should be considered for administration of probiotics but to date, no studies exist on the influence of geometric factors of the tableting tool and of the tablets on the survival of microorganisms. To address this aspect, the survival of <em>Saccharomyces cerevisiae</em> during the production of flat, round tablets with different tablet masses and thus heights as well as differently shaped convex tablets is determined and related to the physical-mechanical tablet properties to derive process-structure-property relationships. It turned out that higher tablet heights were advantageous regarding microbial survival and mechanical strength which is attributed to a lower elastic recovery. However, the use of differently shaped tools had a smaller influence on microbiological and mechanical tablet properties since the global tablet porosity was hardly affected.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100332"},"PeriodicalIF":5.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799764","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

An iterative process and mixture design approach for dry granulated ternary blends of filler-binders 填料-粘结剂干燥颗粒状三元共混物的迭代过程及混合物设计方法

IF 5.2 2区医学

International Journal of Pharmaceutics: X Pub Date : 2025-04-01 DOI: 10.1016/j.ijpx.2025.100331

Niclas Märkle , Gernot Warnke , Miriam Pein-Hackelbusch

{"title":"An iterative process and mixture design approach for dry granulated ternary blends of filler-binders","authors":"Niclas Märkle , Gernot Warnke , Miriam Pein-Hackelbusch","doi":"10.1016/j.ijpx.2025.100331","DOIUrl":"10.1016/j.ijpx.2025.100331","url":null,"abstract":"<div><div>Roller compaction/dry granulation (RC/DG) is a key process in pharmaceutical manufacturing for improving powder flowability, density, and segregation resistance. Advanced statistical modeling was used to optimize RC/DG process parameters and subsequently binder compositions by employing process and mixture design experiments. The authors used microcrystalline cellulose (MCC), silicified MCC (SMCC), and dicalcium phosphate (DCP) as filler-binder examples in RC/DG experiments. Granule and tablet properties, including flowability, bulk and tapped densities, as well as resistance to crushing, were analyzed using compendial methods. The process design experiments confirmed that RC/DG reduces manufacturability compared to direct compression. Optimal processing conditions, balancing sufficient tablet strengths and granule formation, were identified to be between 20 (SCF * ϑ) [kN/cm] and ∼ 60 (SCF * ϑ) [kN/cm]. Thereby (ϑ) is defined as the screw-to-roll speed ratio and (SFC) as the specific compaction force. Mixture design experiments revealed optimal mixtures balancing SMCC, MCC, and DCP to achieve desired properties like low angle of repose, high bulk density, and strong tablets. These findings provide guidance for selecting formulations and process parameters in RC/DG applications. The derived ‘SCF * ϑ’- factor was found to effectively describe the granulation intensity. A superimposed mixture design model based on precise target values of the parameters bulk density, flow properties, and breaking force allowed identification of the best formulation.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100331"},"PeriodicalIF":5.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776954","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

Polycarboxybetaine in advanced drug delivery systems: From structure-function relationship to therapeutic applications 聚羧基甜菜碱在先进的药物输送系统：从结构-功能关系到治疗应用

IF 5.2 2区医学

International Journal of Pharmaceutics: X Pub Date : 2025-03-29 DOI: 10.1016/j.ijpx.2025.100329

Zhuang Liu , Yanan Zhai , Shunye Wang, Jiahui Bai, Dan Wang, Ziyang Wang, Xiang Gao, Jing Gao

{"title":"Polycarboxybetaine in advanced drug delivery systems: From structure-function relationship to therapeutic applications","authors":"Zhuang Liu , Yanan Zhai , Shunye Wang, Jiahui Bai, Dan Wang, Ziyang Wang, Xiang Gao, Jing Gao","doi":"10.1016/j.ijpx.2025.100329","DOIUrl":"10.1016/j.ijpx.2025.100329","url":null,"abstract":"<div><div>Zwitterionic polycarboxybetaines (PCBs), combining quaternary ammonium cations and carboxylate anions in their repeating units, have emerged as promising materials for drug delivery applications. Their exceptional hydration, biocompatibility, and antifouling properties make them attractive alternatives to polyethylene glycol (PEG), particularly given growing concerns about immunogenicity of PEG. PCBs can be functionalized through various methods, including modification of side-chain moieties, adjustment of spacer length between charged groups, and incorporation of responsive elements. When applied to delivery drug, PCBs have been successfully developed into multiple formats including micelles, hydrogels, liposomes, and nanoparticles. Notably, in protein drug delivery, PCBs demonstrate significant advantages such as enhancing protein stability, extending circulation time, improving penetration through biological barriers, and reducing immunogenicity. Despite these promising features, several challenges remain, including complex synthesis requirements, limited mechanical properties, and pending FDA approval as pharmaceutical excipients. This review provides a comprehensive analysis of PCBs from the structure-function relationship, synthesis methods, and applications in drug delivery systems, while examining current limitations and future prospects.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100329"},"PeriodicalIF":5.2,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747097","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

Enrofloxacin‑silver composite nano-emulsion as a scalable synergetic antibacterial platform for accelerating infected wound healing 恩诺沙星-银复合纳米乳剂作为加速感染伤口愈合的可扩展协同抗菌平台

IF 5.2 2区医学

International Journal of Pharmaceutics: X Pub Date : 2025-03-25 DOI: 10.1016/j.ijpx.2025.100330

Jiahao Gong , Moxin Liu , Runan Zuo , Xinhao Song , Junqi Wang , Qindan Zuo , Yan Jiang , Yunfeng Long , Yuzhen Silang , Zeng Luo , Xiuge Gao , Dawei Guo

{"title":"Enrofloxacin‑silver composite nano-emulsion as a scalable synergetic antibacterial platform for accelerating infected wound healing","authors":"Jiahao Gong , Moxin Liu , Runan Zuo , Xinhao Song , Junqi Wang , Qindan Zuo , Yan Jiang , Yunfeng Long , Yuzhen Silang , Zeng Luo , Xiuge Gao , Dawei Guo","doi":"10.1016/j.ijpx.2025.100330","DOIUrl":"10.1016/j.ijpx.2025.100330","url":null,"abstract":"<div><div>The colonization of bacterial pathogens is a major concern in wound infection and becoming a notable medical issue. Enrofloxacin (ENR) can be applied to treat skin infections, while poor water solubility and bioavailability limit its clinical application. Nanostructured lipid carriers (NLCs) enhance the solubility and bioavailability of drugs by encapsulating them, making them effective for the topical treatment of skin wound infections. Additionally, to enhance treatment efficacy and further improve wound healing, silver nanoparticles (AgNPs) were attached to the aforementioned matrix, which also improved its colloidal stability and reduced toxicity. Herein, a scalable poly (vinyl alcohol) modified NLCs-based antibacterial platform was fabricated by high-pressure homogenization method, to co-load ENR and AgNPs for treating the bacterial-infected wounds. The growth of common wound bacterial pathogens (<em>Escherichia coli</em>, <em>Staphylococcus aureus</em> and <em>Pseudomonas aeruginosa</em>) was synergistically inhibited by released ENR and Ag<sup>+</sup> from the poly (vinyl alcohol) modified enrofloxacin‑silver composite nano-emulsion (ENR@PVA-NLCs/AgNPs). In the <em>in vivo</em> wound model, the <em>Staphylococcus aureus</em>-infected wound in rat almost completely disappeared after treatment with ENR@PVA-NLCs/AgNPs, and no suppuration symptom was observed. Importantly, this nanoplatform had negligible side effects <em>in vivo</em>. Taken together, the above results strongly demonstrate the promising potential of ENR@PVA-NLCs/AgNPs as a synergistic therapeutic agent for clinical wound infections.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100330"},"PeriodicalIF":5.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714285","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

Advanced healing potential of simple natural hydrogel loaded with sildenafil in combating infectious wounds 负载西地那非的纯天然水凝胶抗感染性伤口的先进愈合潜力

IF 5.2 2区医学

International Journal of Pharmaceutics: X Pub Date : 2025-03-24 DOI: 10.1016/j.ijpx.2025.100328

Yifan Lai , Wa Zhang , Yizhang Chen , Jialu Weng , Yuhan Zeng , Shunfu Wang , Xiaoying Niu , Meilin Yi , Haobing Li , Xuchen Deng , Xiuhua Zhang , Danyun Jia , Wenzhang Jin , Fajing Yang

{"title":"Advanced healing potential of simple natural hydrogel loaded with sildenafil in combating infectious wounds","authors":"Yifan Lai , Wa Zhang , Yizhang Chen , Jialu Weng , Yuhan Zeng , Shunfu Wang , Xiaoying Niu , Meilin Yi , Haobing Li , Xuchen Deng , Xiuhua Zhang , Danyun Jia , Wenzhang Jin , Fajing Yang","doi":"10.1016/j.ijpx.2025.100328","DOIUrl":"10.1016/j.ijpx.2025.100328","url":null,"abstract":"<div><div>Infected wounds are common clinical injuries that often complicated by inflammation and oxidative stress due to bacterial invasion. These wounds typically suffer from impaired vascularization, which delays healing and increases the risk of complications such as sepsis and chronic wounds. Therefore, developing an effective treatment for infected wounds is highly necessary. Egg white can promote cell regeneration and repair, while chitosan is effective in resisting bacterial invasion. Sildenafil is believed to have the potential to promote angiogenesis. Based on these properties, we have prepared a new type of hydrogel using egg white and chitosan as the framework, loaded with sildenafil (CEHS). The hydrogel combines the benefits of its components, exhibiting good biocompatibility and promoting the proliferation and migration of NIH 3T3 (3T3) cells and human umbilical vein endothelial cells (HUVEC), as well as the angiogenesis in HUVEC. It also exhibits significant antioxidant, anti-inflammatory, and antibacterial properties against <em>Escherichia coli (E. coli)</em> and <em>Staphylococcus aureus (S. aureus)</em>. Additionally, in a mouse model of infected wounds, the CEHS effectively promoted wound healing through its excellent antioxidant and anti-inflammatory properties, antibacterial activity, and pro-angiogenic effects. In summary, this simple-to-prepare, multifunctional natural hydrogel shows great promise for the treatment of infected wounds.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100328"},"PeriodicalIF":5.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726016","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

Comparing the transfection efficiency of cationic monomer ratios in vinylimidazole and aminoethyl methacrylate copolymers 比较阳离子单体比例在乙烯咪唑和甲基丙烯酸氨基乙酯共聚物中的转染效率

IF 5.2 2区医学

International Journal of Pharmaceutics: X Pub Date : 2025-03-04 DOI: 10.1016/j.ijpx.2025.100327

Sahel Soghrati , Jaleh Varshosaz , Mahboubeh Rostami , Mina Mirian , Fariborz Sharifianjazi , Ketevan Ta-vamaishvili

{"title":"Comparing the transfection efficiency of cationic monomer ratios in vinylimidazole and aminoethyl methacrylate copolymers","authors":"Sahel Soghrati , Jaleh Varshosaz , Mahboubeh Rostami , Mina Mirian , Fariborz Sharifianjazi , Ketevan Ta-vamaishvili","doi":"10.1016/j.ijpx.2025.100327","DOIUrl":"10.1016/j.ijpx.2025.100327","url":null,"abstract":"<div><div>Employing polycations as non-viral gene delivery vectors has been extensively studied owing to their safety, efficiency and possibility of modifying them in an intended way compared with viral vectors. However, the main challenge is finding a biocompatible and transfection-efficient polymer. In this study, 2-aminoethyl methacrylate (A) and 1-vinyl imidazole (V) were copolymerized at three different molar ratios by a free radical polymerization method and novel biocompatible polycations with narrow molecular weight distribution were obtained. The resulting copolymers were used for condensation of plasmid DNA (pDNA) at different N/P ratios followed by physicochemical characterizations of resulting polyplexes. At N/P ratio of 2, the nanoplexes were smaller than 120 nm. The optimum formulations were stable in presence of polyanions and capable of protecting the condensed pDNA against nucleases. The polyplexes having V to A molar ratio of 1:1 were the most efficient carrier in transfecting HeLa cells and were introduced as a promising non-viral vector.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100327"},"PeriodicalIF":5.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563468","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

Reticuloendothelial system blockade does not enhance siRNA-LNP circulation or tumor accumulation in mice 网状内皮系统阻断不会增强 siRNA-LNP 在小鼠体内的循环或肿瘤蓄积

IF 5.2 2区医学

International Journal of Pharmaceutics: X Pub Date : 2025-02-27 DOI: 10.1016/j.ijpx.2025.100324

Pol Escudé Martinez de Castilla , Mariona Estapé Senti , Sigrun Erkens , Wytske M. van Weerden , Sander A.A. Kooijmans , Marcel H. Fens , Pieter Vader , Raymond M. Schiffelers

{"title":"Reticuloendothelial system blockade does not enhance siRNA-LNP circulation or tumor accumulation in mice","authors":"Pol Escudé Martinez de Castilla , Mariona Estapé Senti , Sigrun Erkens , Wytske M. van Weerden , Sander A.A. Kooijmans , Marcel H. Fens , Pieter Vader , Raymond M. Schiffelers","doi":"10.1016/j.ijpx.2025.100324","DOIUrl":"10.1016/j.ijpx.2025.100324","url":null,"abstract":"<div><div>One of the biggest challenges for siRNA-based therapeutics is intracellular delivery into the target cell, which can be facilitated by encapsulating siRNA in lipid nanoparticles (LNPs). In this study, we formulated D-Lin-MC3-DMA-LNPs encapsulating siRNA against the androgen receptor (AR), a key driver in prostate cancer. We effectively knocked down AR expression at both the mRNA as well as protein levels <em>in vitro</em> in AR-expressing prostate cancer cell lines. However, when moving to <em>in vivo</em> studies, siRNA-LNP efficacy is hindered by rapid clearance by the reticuloendothelial system (RES) in the liver and spleen. We evaluated whether transient RES blockade through systemic pre-administration of dextran sulfate or liposomes could extend the circulation time and enhance tumor accumulation of siRNA-LNPs in tumor-bearing mice. In two different mouse prostate cancer (PCa) xenograft models, we observed that, upon systemic administration, LNPs still predominantly accumulated in the liver and spleen, with only limited tumor uptake. Our findings demonstrate that pre-treatment with dextran sulfate or liposomes did not enhance siRNA-LNP blood circulation time or tumor accumulation <em>in vivo</em>, indicating the need for alternative strategies to enhance siRNA-LNP delivery to tumors.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100324"},"PeriodicalIF":5.2,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528776","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