International Journal of Pharmaceutics最新文献_第6页

Smart stimuli-responsive hydrogels for safe oral administration of Insulin: A Review

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-03-17 DOI: 10.1016/j.ijpharm.2025.125487

Nan Jiang , Xiangjun Yu , Jing Zhang , Yunbao Zhang , Li Li , Yu Liu

引用次数: 0

Development of an ex vivo human skin model and evaluation of biological responses to subcutaneously injected hyaluronic acid formulations

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-03-17 DOI: 10.1016/j.ijpharm.2025.125490

Si Gou , Yogeshvar N. Kalia

{"title":"Development of an ex vivo human skin model and evaluation of biological responses to subcutaneously injected hyaluronic acid formulations","authors":"Si Gou , Yogeshvar N. Kalia","doi":"10.1016/j.ijpharm.2025.125490","DOIUrl":"10.1016/j.ijpharm.2025.125490","url":null,"abstract":"<div><div>We have previously described a model using porcine ear skin <em>ex vivo</em> for longitudinal studies into the disposition of macromolecules after subcutaneous injection. Since porcine skin cannot fully mimic biological responses in human skin, we now describe an <em>ex vivo</em> system using “full thickness” human skin. Spongiosis and epidermal detachment were the primary endpoints to evaluate skin structural integrity over a 9-day culture period. Epidermal barrier function and basal cell proliferation were monitored using expression of claudin-1 and Ki-67, respectively. Immunofluorescent staining of type I and type III procollagens and elastin after subcutaneous injection of TGF-β3, a cross-linked hyaluronic acid hydrogel, and saline solution and “no treatment” controls, showed that the model enabled visualization of changes in extracellular matrix proteins. Semi-quantitative, automated image analysis methods using multiple ROIs were evaluated to assess signal intensity and expression area of type I procollagen but displayed high inter-regional variability due to skin sample heterogeneity. Absolute quantitative methods, e.g. RT-qPCR or ELISA, which enable determination of biomarkers at either the mRNA level or the amounts of protein expressed in the sample, could be a better reporting tool. In conclusion, we successfully developed an <em>ex vivo</em> “full thickness” human skin model that retained viability over 9 days and which could be deployed in combination with qualitative/quantitative methods to evaluate local biological effects of subcutaneously injected biomacromolecules.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"674 ","pages":"Article 125490"},"PeriodicalIF":5.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662682","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

Baicalein nanoemulsion in situ GEL for dry age-related macular degeneration

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-03-17 DOI: 10.1016/j.ijpharm.2025.125494

Wanbing Pan , Rong Sun , Yaoyuan Yu , Yuxin Liu , Yinling Mu , Hanyan Gong , Hongxia Fan , Yingchao Zhang , Lutong He , Haibing He , Jingxin Gou , Xing Tang , Tian Yin , Yu Zhang

{"title":"Baicalein nanoemulsion in situ GEL for dry age-related macular degeneration","authors":"Wanbing Pan , Rong Sun , Yaoyuan Yu , Yuxin Liu , Yinling Mu , Hanyan Gong , Hongxia Fan , Yingchao Zhang , Lutong He , Haibing He , Jingxin Gou , Xing Tang , Tian Yin , Yu Zhang","doi":"10.1016/j.ijpharm.2025.125494","DOIUrl":"10.1016/j.ijpharm.2025.125494","url":null,"abstract":"<div><div>Effective management of posterior ocular segment disorders necessitates sustained retinal drug delivery and rational therapeutic selection. Despite significant advances, developing drug delivery systems that simultaneously achieve deep tissue penetration and prolonged ocular surface retention remains challenging. To bridge this gap, we engineered a borneol- decorated baicalein nanoemulsion in-situ gel (Bor/Bai-N@GEL) ophthalmic formulation for dry age-related macular degeneration (d-AMD). The system integrates a borneol-decorated baicalein nanoemulsion with an ion- sensitive hydrogel. Comparative analysis revealed Bor/Bai-N@GEL’s superior therapeutic performance, attributable to the prolonged ocular residence time and enhanced transcorneal permeability. Pharmacodynamic profiling demonstrated marked attenuation of inflammatory cytokines, oxidative markers, and apoptotic signaling in murine d-AMD models. In summary, our work provided a meaningful delivery strategy and research basis to treat fundus diseases. This approach offers the potential to conveniently treat early-stage d-AMD at home, improving patient adherence and overall treatment outcomes.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"675 ","pages":"Article 125494"},"PeriodicalIF":5.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662476","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

Development of a messenger RNA vaccine using pH-responsive dipeptide-conjugated lipids exhibiting reduced inflammatory properties

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-03-16 DOI: 10.1016/j.ijpharm.2025.125485

Katsuki Matayoshi , Sayaka Takahashi , Sohei Ryu , Hiroyuki Koide , Sei Yonezawa , Nahoko Ozaki , Makiko Kurata , Tomohiro Asai

{"title":"Development of a messenger RNA vaccine using pH-responsive dipeptide-conjugated lipids exhibiting reduced inflammatory properties","authors":"Katsuki Matayoshi , Sayaka Takahashi , Sohei Ryu , Hiroyuki Koide , Sei Yonezawa , Nahoko Ozaki , Makiko Kurata , Tomohiro Asai","doi":"10.1016/j.ijpharm.2025.125485","DOIUrl":"10.1016/j.ijpharm.2025.125485","url":null,"abstract":"<div><div>Lipid nanoparticles (LNPs) are used to encapsulate messenger ribonucleic acids (mRNAs) and enhance mRNA vaccine efficacy by producing inflammatory mediators. However, the overproduction of inflammatory mediators via LNP injection causes severe side effects, presenting a potential limitation. To resolve this issue, we developed pH-responsive dipeptide-conjugated lipid (DPL)-based LNPs (DPL–LNPs) for efficient small interfering RNA delivery with excellent biocompatibility. In detail, we optimized the dipeptide sequence and lipid-tail length of DPL, the helper-lipid compositions, and the molecular weight and lipid-tail length of the polyethylene glycol (PEG)–lipid to achieve highly efficient and safe mRNA delivery. Our results revealed that the LNPs prepared using glutamic acid (E)- and arginine (R)-conjugated DPL (DPL–ER) displayed higher protein-expression efficacy than DPL–threonine–R- and DPL–aspartic acid–R-based LNPs. Additionally, the lipid-tail length of the C22-bearing DPL–ER (DPL–ER–C22)-based LNPs displayed higher protein-expression efficacies than their C18 (DPL–ER–C18)- and C24 (DPL–ER–C24)-based LNPs. Moreover, the DPL–ER–C22-based LNPs incorporating low-lipid-tail-length phospholipids and PEG–lipids exhibited efficient protein expression. Most importantly, the injection of optimized DPL–LNPs exhibited comparable antigen-specific antibody production levels, with significantly lower inflammatory-mediator production compared with those of the commercially available LNPs. These results indicate that DPL-based LNPs (DPL–LNPs) can be deployed as highly efficient, safe carriers for mRNA delivery for developing mRNA vaccine formulations.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"674 ","pages":"Article 125485"},"PeriodicalIF":5.3,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657033","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

Construction and application of macrophage-based extracellular drug-loaded delivery systems

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-03-16 DOI: 10.1016/j.ijpharm.2025.125462

Fangyuan Guo , Yujia Wang , Jialin Chen , Ruorong Wang , Lianyi Wang , Weiyong Hong , Yinzhou Du , Gensheng Yang

引用次数: 0

Continuous preparation of long-acting hydromorphone PLGA microspheres using an automatic and scalable microfluidic process system

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-03-16 DOI: 10.1016/j.ijpharm.2025.125459

Quan Liu , Huiting Liu , Haoxiang Wu , Yongzhuo Huang , Hao Wang , Fuli Zhang

{"title":"Continuous preparation of long-acting hydromorphone PLGA microspheres using an automatic and scalable microfluidic process system","authors":"Quan Liu , Huiting Liu , Haoxiang Wu , Yongzhuo Huang , Hao Wang , Fuli Zhang","doi":"10.1016/j.ijpharm.2025.125459","DOIUrl":"10.1016/j.ijpharm.2025.125459","url":null,"abstract":"<div><div>The long-acting hydromorphone loaded poly-lactic-co-glycolic acid (HM-PLGA) microspheres for chronic pain management were developed and prepared using an automatic and scalable microfluidic process system in this study. The system consists of a novel designed micro-mixer for particle generation, syringe and HPLC pumps for continuous dosing, a process Raman spectrometer as process analytical technology (PAT) tool and an automation system for programmable automatic control. With the benefits of the automation and digitalization of the system, a wide range of formulation parameters was investigated for its impact on the properties of the microspheres. The particle size of the HM-PLGA microspheres was tunable with the automatic microfluidic process system. The long-acting injectable homogeneous HM-PLGA microspheres were successfully prepared with maximum drug-loading capacity of 7.71 % and drug encapsulation efficiency of 69.40 %. The physical and chemical properties were characterized using various analytical technologies. Pharmacokinetic experiments in female ICR mice confirmed prolonged exposure in plasma compared to the HM hydrochloride injection. In vivo studies in beagle dogs showed that the HM-PLGA microspheres provided sustained drug release for over 11 days. The results demonstrated the potential of the novel automatic microfluidic process system in the development and continuous manufacturing of the particle size-controllable drug loaded microspheres.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"674 ","pages":"Article 125459"},"PeriodicalIF":5.3,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657027","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

Innovative centrifugal microfluidic approach for risperidone-loaded PLGA microsphere production

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-03-16 DOI: 10.1016/j.ijpharm.2025.125484

Bingwen Zhang , Haofan Liu , Yixuan Li , Tong Cao , Jinkuo Cao , Liandong Hu

{"title":"Innovative centrifugal microfluidic approach for risperidone-loaded PLGA microsphere production","authors":"Bingwen Zhang , Haofan Liu , Yixuan Li , Tong Cao , Jinkuo Cao , Liandong Hu","doi":"10.1016/j.ijpharm.2025.125484","DOIUrl":"10.1016/j.ijpharm.2025.125484","url":null,"abstract":"<div><div>This paper proposes a novel and efficient centrifugal microfluidic technology to prepare risperidone-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (RIS-MS). The effects of key parameters, including PLGA concentration and type, microchannel inner diameter and centrifugal speed on particle size, morphology and drug release were evaluated and optimized. The <em>in vivo</em> pharmacokinetic study of RIS-MS was conducted in rabbits. The results demonstrated that RIS-MS could be produced from microchannels with inner diameters of 170–210 μm at a centrifugal speed of 400 revolutions per minute (rpm) when the PLGA content is 15 % or higher. The mean plasma concentration of RIS-MS was more stable and C<sub>max</sub> of RIS-MS was significantly lower than that of the suspension group, and the RIS-MS could maintain the release of RIS in rabbits for up to 42 days. This study provided pioneering ideas for developing microspheres using centrifugal microfluidic technology. The optimized RIS-MS can make excellent sustained release and have the potential for the long-acting therapy of schizophrenia.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"674 ","pages":"Article 125484"},"PeriodicalIF":5.3,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643015","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

CD44-targeted nanoparticles for remodeling the tumor microenvironment in a 3D macrophage-embedded ovarian cancer model with stem cell-like features

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-03-16 DOI: 10.1016/j.ijpharm.2025.125483

Samjhana Shrestha , Anil Giri , Prabhat Shrestha , Seho Kweon , In-Sun Hong , Taeg Kyu Kwon , Jong-Sun Kang , Jee-Heon Jeong , Ha Rin Kim , Simmyung Yook

{"title":"CD44-targeted nanoparticles for remodeling the tumor microenvironment in a 3D macrophage-embedded ovarian cancer model with stem cell-like features","authors":"Samjhana Shrestha , Anil Giri , Prabhat Shrestha , Seho Kweon , In-Sun Hong , Taeg Kyu Kwon , Jong-Sun Kang , Jee-Heon Jeong , Ha Rin Kim , Simmyung Yook","doi":"10.1016/j.ijpharm.2025.125483","DOIUrl":"10.1016/j.ijpharm.2025.125483","url":null,"abstract":"<div><div>Ovarian cancer frequently develops resistance to chemotherapy, which is driven by cancer stem cells (CSCs) and an immunosuppressive tumor microenvironment (TME) shaped by tumor-associated macrophages (TAMs). This study explored the therapeutic potential of CD44-targeted, docetaxel (DTX)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CD44-PLGA-DTX NPs) in overcoming chemoresistance in ovarian cancer.</div><div>A 3D spheroidal model incorporating SKOV3 ovarian cancer cells and TAMs was developed to mimic the TME for <em>in vitro</em> investigations. CD44-PLGA-DTX NPs exhibited significantly enhanced cellular uptake within the macrophage-embedded SKOV3 spheroids, which resulted in reduced cell viability and a reversal of chemoresistance. Cytokine profiling further revealed that the NPs promoted TAM polarization from the protumor M2 phenotype to the antitumor M1 phenotype, thus fostering an antitumor immune environment. These findings highlight the potential of CD44-targeted NPs as a dual-targeted therapeutic strategy, targeting both CSCs-driven tumor growth and TME reprogramming, thereby improving ovarian cancer treatment outcomes.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"674 ","pages":"Article 125483"},"PeriodicalIF":5.3,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656971","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

Study of shape of zinc oxide nanoparticles on the in-vitro and in-vivo performance of polymeric hydrogels for wound dressing

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-03-15 DOI: 10.1016/j.ijpharm.2025.125482

Hizbullah Malik , Fatima Amir , Zaib Jahan , Usman Liaqat , Saadia Andleeb , Sulalit Bandyopadhyay , Muhammad Bilal Khan Niazi

{"title":"Study of shape of zinc oxide nanoparticles on the in-vitro and in-vivo performance of polymeric hydrogels for wound dressing","authors":"Hizbullah Malik , Fatima Amir , Zaib Jahan , Usman Liaqat , Saadia Andleeb , Sulalit Bandyopadhyay , Muhammad Bilal Khan Niazi","doi":"10.1016/j.ijpharm.2025.125482","DOIUrl":"10.1016/j.ijpharm.2025.125482","url":null,"abstract":"<div><div>Extensive fluid loss, tissue damage, and bacterial infection are some important aspects that need to be addressed for designing ideal burn wound dressings. Hydrogel-based dressings cater to most of these functions; additionally, the incorporation of metal oxide nanoparticles (NPs) provides antibacterial properties that enhance the performance of wound dressings. We report here for the first time, how by employing different shapes of ZnO NPs, viz quasi-spherical, floral, and rods; in hydrogels made of PVA – P(AMPS) (Poly (vinyl alcohol) (PVA) − Poly (2-Acrylamido-2-Methyl Propane Sulfonic Acid)) along with g-C<sub>3</sub>N<sub>4</sub>, one could correlate structure–property relationships to wound healing efficiency. The incorporation of g-C3N4 was to enhance the thermo-mechanical stability of hydrogel, Maximum tensile strength of the hydrogel was obtained for 150 mg of g-C3N4 incorporated hydrogels, same amount being used for other systems studied. The impact of the incorporation of different shapes and amounts of ZnO NPs on the hydrogels has been studied and our results show maximum swelling ability (∼110 %), high moisture retention capacity (>90 %), and moderate water vapor transmission rate (82 g/m<sup>2</sup>h) for selected systems. Among these different shapes incorporated hydrogels, remarkable enhancement in tensile strength (76 %) was observed for quasi-spherical ZnO NPs incorporated hydrogels compared to bare. These hydrogels showed high cell viability (>70 %), high antibacterial activities against <em>E. coli</em> and <em>S. aureus,</em> and high wound healing efficiency (>80 %) in an <em>in-vivo</em> rat model, proving their potential to be used in wound dressing applications.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"674 ","pages":"Article 125482"},"PeriodicalIF":5.3,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648578","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

Corrigendum to “Development of silk fibroin/collagen film containing GI-20 peptide-loaded PLGA nanoparticles against corneal herpes simplex virus-1” [Int. J. Pharm. 669 (2025) 125022] 蚕丝纤维素/胶原蛋白薄膜含 GI-20 肽负载 PLGA 纳米粒子抗角膜单纯疱疹病毒-1 的开发》[Int. J. Pharm. 669 (2025) 125022]更正

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-03-15 DOI: 10.1016/j.ijpharm.2025.125369

Razieh Sohrabi , Amir Hossein Miri , Mazda Rad-Malekshahi , Fatemeh Saadatpour , Bahareh Pourjabbar , Saeed Heidari Keshel , Ehsan Arefian , Saeed Balalaei , Ahmad Massomi , Fereshte Khalili , Ismaeil Haririan , Mohammad Akrami , Mohammad Hassan Shahriari

引用次数: 0