International Journal of Pharmaceutics最新文献_第2页

Preparation of self-dispersible eutectic mixtures for poorly soluble drugs: Hot-melt extrusion vs. melt casting 难溶性药物用自分散共晶混合物的制备：热熔挤压与熔融铸造

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-05-03 DOI: 10.1016/j.ijpharm.2025.125637

Peter Schlosser, Heike Bunjes

{"title":"Preparation of self-dispersible eutectic mixtures for poorly soluble drugs: Hot-melt extrusion vs. melt casting","authors":"Peter Schlosser, Heike Bunjes","doi":"10.1016/j.ijpharm.2025.125637","DOIUrl":"10.1016/j.ijpharm.2025.125637","url":null,"abstract":"<div><div>Solid eutectic mixtures of self-dispersible polyethylene glycol-40-stearate with fenofibrate or ibuprofen – prepared by casting or by twin-screw extrusion – were compared in terms of processability and dissolution rate at, below, and above the eutectic concentration. Furthermore, the effects of extruding with two distinct screw configurations – a shear screw and a conveyor screw – were investigated. The eutectic mixtures containing ibuprofen had a poor recrystallization tendency and therefore did not yield the desired solid state in the casting process. In contrast, they could be successfully processed by extrusion due to the initiation of recrystallization by friction and shear forces. Fenofibrate-containing solid mixtures were obtained by both methods. The extrudates of all mixtures showed a decreasing API particle size (d50 ∼ 6 to 9 µm) with increasing API concentration up to a certain threshold. For the extrudates containing ibuprofen, smaller API particle sizes were obtained with the conveyor screw; for the fenofibrate extrudates, however, the particle sizes were similar regardless of the screw configuration. Compared to the physical mixtures and the pure API, all cast samples and extrudates exhibited a considerably higher dissolution rate, depending on the excipient to API ratio. Despite the differences in particle size, similar dissolution profiles were observed for the ibuprofen extrudates produced by both conveyor and shear screws. For the fenofibrate mixtures, the dissolution profiles were similar for both screw configurations as well as for the cast references below and at the eutectic concentration. The dissolution rate was superior for the extrudates containing fenofibrate above the eutectic concentration.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"677 ","pages":"Article 125637"},"PeriodicalIF":5.3,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924798","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

Automated process development with pure API filling using vacuum drum 使用真空滚筒进行纯API灌装的自动化工艺开发

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-05-03 DOI: 10.1016/j.ijpharm.2025.125665

Isabel Gallego , Thomas Brinz , Martin Sommerfeld

{"title":"Automated process development with pure API filling using vacuum drum","authors":"Isabel Gallego , Thomas Brinz , Martin Sommerfeld","doi":"10.1016/j.ijpharm.2025.125665","DOIUrl":"10.1016/j.ijpharm.2025.125665","url":null,"abstract":"<div><div>In pharmaceutical development, dosing of pure active pharmaceutical ingredient (API) has proven to be essential for reducing API consumption and shortening early-stage development time, avoiding the need for excipients and compatibility studies. The vacuum drum filler, known for its precision in dosing down to 1 mg, is commonly employed for micro-dosing purposes, e.g., in the field of dry powder inhalation (DPI). In this study, however, it is desired to investigate the vacuum drum filler for its suitability in pure API filling. Automated Process Development (APD) integrates design of experiments (DoE) with automated execution to optimize processes efficiently. In this study, the APD method was investigated on the vacuum drum filling system to analyse the impact of various process parameters on the filling weight of capsules and the relative standard deviation (RSD) between the bores considering pure API. For this, two APIs were investigated: powdered paracetamol and micronized paracetamol. Notably, despite variations in vacuum and pressure, process parameters related to powder preparation in the chamber exerted the most significant influence. The 3-wire stirrer, located in the chamber on top of the vacuum drum, resulted in better filling weights and lower RSD with both powders. The APD method allowed to identify the parameters that minimized the RSD in the capsule filling of pure powdered paracetamol, emphasizing the need for tailored parameter optimization. Further investigation is needed to determine how to achieve optimal powder preparation in the chamber for micronized paracetamol.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"678 ","pages":"Article 125665"},"PeriodicalIF":5.3,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929642","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

Dissolving microneedle patch integrated with microparticle depots for sustained intradermal delivery of donepezil 溶解微针贴片与微粒储存库集成持续皮内给药多奈哌齐

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-05-02 DOI: 10.1016/j.ijpharm.2025.125653

Jae Hwan Lee , Geun Jin Song , Hee Sook Hwang , Chung-Sung Lee

{"title":"Dissolving microneedle patch integrated with microparticle depots for sustained intradermal delivery of donepezil","authors":"Jae Hwan Lee , Geun Jin Song , Hee Sook Hwang , Chung-Sung Lee","doi":"10.1016/j.ijpharm.2025.125653","DOIUrl":"10.1016/j.ijpharm.2025.125653","url":null,"abstract":"<div><div>Alzheimer’s Disease (AD) is a significant global health challenge worldwide and imposes a substantial economic burden. Due to the shortcomings of conventional pharmaceutical formulations (e.g., tablet and microparticle depot injection), such as low bioavailability, frequent dosing, and the inconvenience related to injection), there is a pressing need to develop a convenient and effective medical cue for AD treatment. Here, a hybrid dissolving microneedle patch integrated with donepezil (DNP)-encapsulated biodegradable microparticle depots is introduced for sustained DNP delivery, reduced dosing frequency, and improved patient compliance. Once the microneedle patch delivers DNP-encapsulated microparticle depots into the skin, they subsequently act as drug reservoirs for the sustained release of the DNP for over 2 weeks. <em>In vitro</em> and <em>ex vivo</em> insertion experiments showed that the microneedle patches could provide enough mechanical strength and good morphology, as well as enhanced dissolvability and retention of microparticle depots in the skin. <em>In vitro</em> cytocompatibility study in NIH3T3 cells demonstrated the biocompatibility of the materials comprising microneedle patch. This hybrid system offers a promising alternative to conventional oral or injectable therapies for AD by enabling self-administrable, pain-free, and long-acting transdermal delivery.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"678 ","pages":"Article 125653"},"PeriodicalIF":5.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918162","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

3D-printed chewable gummy tablets: A new tool for oral amoxicillin administration in paediatric population 3d打印咀嚼软糖片：儿科口服阿莫西林给药的新工具

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-05-02 DOI: 10.1016/j.ijpharm.2025.125645

Anna Imbriano , Costanza Fratini , Giulia Bondi , Ilenia D’Abbrunzo , Serena Bertoni , Mattia Tiboni , Angela Abruzzo , Dritan Hasa , Cinzia Pagano , Luca Casettari

{"title":"3D-printed chewable gummy tablets: A new tool for oral amoxicillin administration in paediatric population","authors":"Anna Imbriano , Costanza Fratini , Giulia Bondi , Ilenia D’Abbrunzo , Serena Bertoni , Mattia Tiboni , Angela Abruzzo , Dritan Hasa , Cinzia Pagano , Luca Casettari","doi":"10.1016/j.ijpharm.2025.125645","DOIUrl":"10.1016/j.ijpharm.2025.125645","url":null,"abstract":"<div><div>Amoxicillin is one of the most prescribed antibiotics in the paediatric population. Currently available formulations (<em>i.e.</em>, suspensions and tablets) suffer from limited acceptability often responsible for the therapeutic failure. In the present study it is proposed an innovative formulation for amoxicillin oral administration that could meet acceptability requirements of the paediatric population. Chewable gummy tablets were produced by the Pressure-Assisted Microsyringe 3D printing technology. As “ink” it was used a gel obtained by the co-formulation of corn starch with acacia honey. The optimized formulation, having a final dose of 200 mg per unit, resulted visually appealing. Good accuracy between the computer-aided design and final 3D-printed product was evident as well. The fabricated gummy tablets (1.07 ± 0.05 g) showed acceptable mechanical properties such as hardness (150.52 ± 5.67 N), and gumminess (68.13 ± 6.51 N) when exposed to simulated salivary fluid. Moreover, the 3D-printed gummy tablets determined the almost complete release of the drug in the gastric environment within 2 h and assured its permeation through the PermeaPad® membranes. The obtained results suggest that 3D printing is a versatile and scalable technology useful in the pharmaceutical industry to fabricate customized chewable formulations as a suitable alternative to conventional formulations for amoxicillin administration in the paediatric population.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"677 ","pages":"Article 125645"},"PeriodicalIF":5.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902413","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

The new cocrystal of molnupiravir-caprolactam discovered by melt crystallization with improved tableting properties 用熔融结晶法发现了新的莫那匹韦-己内酰胺共晶，其片化性能得到了改善

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-05-01 DOI: 10.1016/j.ijpharm.2025.125661

Peizhuo Han , Lei Wang , Huimin Li , Changlin Yao , Yaqian Qu , Xu Zhang , Hanlin Zhao , Yaqi Ren , Bozhang Li , Lufeng Xu , Weiguo Song , Xutang Tao

{"title":"The new cocrystal of molnupiravir-caprolactam discovered by melt crystallization with improved tableting properties","authors":"Peizhuo Han , Lei Wang , Huimin Li , Changlin Yao , Yaqian Qu , Xu Zhang , Hanlin Zhao , Yaqi Ren , Bozhang Li , Lufeng Xu , Weiguo Song , Xutang Tao","doi":"10.1016/j.ijpharm.2025.125661","DOIUrl":"10.1016/j.ijpharm.2025.125661","url":null,"abstract":"<div><div>Molnupiravir (MPV) is an oral antiviral drug widely used for the treatment of coronavirus disease 2019 (COVID-19). However, the commercial form I of MPV has a poor tabletability, greatly restricting its manufacture. To solve this problem, a new cocrystal named MPV-caprolactam (CPL) was discovered by melt crystallization, and its crystal structure was successfully determined by single crystal X-ray diffraction. Meanwhile, the formation mechanism of the MPV-CPL cocrystal was studied via the formation enthalpies, and the negative formation enthalpy (−27.61 J/g at 25 ℃) is responsible for the crystallization of the MPV-CPL cocrystal. Finally, the powder tableting properties of the MPV-CPL cocrystal were investigated, and the MPV-CPL cocrystal has superior tabletability, achieving a tensile strength of 2.06 ± 0.09 MPa at 262.5 MPa compression pressure — a 1.93-fold increase over pure MPV. The MPV-CPL cocrystal also shows good compressibility, compactibility, and plasticity. This work establishes two key advances: (1) melt crystallization is a supplement to solution methods, and it can produce pharmaceutical cocrystals that tend to form solvates in solution, and (2) the improvement in tabletability of MPV-CPL cocrystal overcomes the main barrier in developing MPV tablets, which makes it a promising candidate for developing MPV tablets.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"677 ","pages":"Article 125661"},"PeriodicalIF":5.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912100","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

Mucoadhesive polymer-coated liposomes as a promising approach to counteract bacteria responsible for aerobic vaginitis 黏附聚合物包覆脂质体作为一种有前途的方法来对抗负责有氧阴道炎的细菌

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-04-30 DOI: 10.1016/j.ijpharm.2025.125667

Sara Lugli , Angela Abruzzo , Carola Parolin , Beatrice Vitali , Maria Laura Bolognesi , Marco Brucale , Francesco Valle , Teresa Cerchiara , Barbara Luppi , Federica Bigucci

{"title":"Mucoadhesive polymer-coated liposomes as a promising approach to counteract bacteria responsible for aerobic vaginitis","authors":"Sara Lugli , Angela Abruzzo , Carola Parolin , Beatrice Vitali , Maria Laura Bolognesi , Marco Brucale , Francesco Valle , Teresa Cerchiara , Barbara Luppi , Federica Bigucci","doi":"10.1016/j.ijpharm.2025.125667","DOIUrl":"10.1016/j.ijpharm.2025.125667","url":null,"abstract":"<div><div>Aerobic vaginitis is an infectious disease characterized by the overgrowth of abnormal vaginal microflora. Conventional local dosage forms are not always effective, due to their inadequate drug release and residence time within the vaginal cavity. Therefore, this study aimed to develop azithromycin (AZT)-loaded liposomes, coated with two mucoadhesive polymers, chitosan (CS) and sodium hyaluronate (HYA), to increase thedrug’s stay at the site of infection and to control its release. Liposomes were developed through the thin film hydration method followed by extrusion and subsequently added to the polymer solution. Later, they were characterized by their size, surface charge, morphology, and encapsulation efficiency. Furthermore, mucoadhesive properties and drug release behavior were investigated at different pH values, e.g., 4.5 and 7.4, mimicking the physiological and pathological conditions, respectively. Finally, antimicrobial tests and <em>in vitro</em> permeation studies were carried out. Results showed size and surface charge variations of coated LP with respect to the uncoated ones, confirming the success of the coating process. LP possessed a good capacity to encapsulate the drug. Among all the formulations, CS-LP demonstrated superior control of drug release and greatest mucoadhesive properties at both tested pHs, as well as the highest drug accumulation inside the vaginal tissue, maintaining at the same time AZT antimicrobial effect. Overall, CS-LP could be proposed as a promising nanocarrier for AZT vaginal delivery, <em>in virtue</em> of its ability to achieve locally a sustained release of drug, helping to lower the dosage and administration frequency, and consequently improving treatment efficacy.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"677 ","pages":"Article 125667"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918378","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

Intranasal administration of in silico designed Rivastigmine mucoadhesive nanoparticles ameliorates scopolamine-induced Alzheimer’s symptoms in mice: Pharmacokinetic and pharmacodynamic evidences 鼻内给药硅设计的利瓦斯汀黏附纳米颗粒改善东莨菪碱诱导的小鼠阿尔茨海默病症状：药代动力学和药效学证据

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-04-30 DOI: 10.1016/j.ijpharm.2025.125635

Vinni Kalra, Om Silakari, Ashok Kumar Tiwary

{"title":"Intranasal administration of in silico designed Rivastigmine mucoadhesive nanoparticles ameliorates scopolamine-induced Alzheimer’s symptoms in mice: Pharmacokinetic and pharmacodynamic evidences","authors":"Vinni Kalra, Om Silakari, Ashok Kumar Tiwary","doi":"10.1016/j.ijpharm.2025.125635","DOIUrl":"10.1016/j.ijpharm.2025.125635","url":null,"abstract":"<div><div>The low oral bioavailability (36 %) of rivastigmine tartrate (RT), and the inconspicuous pharmacological target site has necessitated the need to explore alternative routes of delivery for effective management of Alzheimer’s disease (AD). The current study aimed to develop <em>in silico</em> designed polymeric nanoparticles (NPs) for the intranasal delivery of RT. Eudragit RL 100 (EDRL) was selected as mucoadhesive polymer because of its optimum binding affinity with RT and nasal mucin. These NPs were prepared using spray drying method by utilizing QbD approach. Yield, particle size, zeta potential, entrapment efficiency and drug loading were optimized using central composite design. Furthermore, the TEM and SEM analysis of RT-EDRL NPs, respectively, revealed the particle size in the range of 50–100 nm and their spherical shape. The <em>in vitro</em> and <em>ex vivo</em> release profiles revealed sustained drug release from RT-EDRL NPs as compared to RT solution. The intranasal administration of optimized NPs exhibited higher RT concentration in mice brain as compared to other routes.</div><div>Higher direct transport percentage (DTP %) and drug targeting efficiency (DTE %) indicated direct transport of RT to the brain through the nose and was better than that observed after application of transdermal patch. The neuroprotective potential conferred by intranasal administration of <em>in silico</em> designed NPs in scopolamine induced amnesia mice seems to be a potential brain targeted delivery system for effective management of AD.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"677 ","pages":"Article 125635"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907126","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

Enhancing efficacy of combretastatin A4 by encapsulation in solid lipid nanoparticles: Implications for anti-angiogenic cancer therapy 用固体脂质纳米颗粒包封增强康布他汀A4的疗效：对抗血管生成癌症治疗的意义

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-04-30 DOI: 10.1016/j.ijpharm.2025.125669

Fariba Bagherieh , Maryam Ebrahimi Nik , Asma Mahmoudi , Leila Gholami , Farzin Hadizadeh , Hamid Reza Sadeghnia , Reza Kazemi Oskuee , Bizhan Malaekeh-Nikouei

{"title":"Enhancing efficacy of combretastatin A4 by encapsulation in solid lipid nanoparticles: Implications for anti-angiogenic cancer therapy","authors":"Fariba Bagherieh , Maryam Ebrahimi Nik , Asma Mahmoudi , Leila Gholami , Farzin Hadizadeh , Hamid Reza Sadeghnia , Reza Kazemi Oskuee , Bizhan Malaekeh-Nikouei","doi":"10.1016/j.ijpharm.2025.125669","DOIUrl":"10.1016/j.ijpharm.2025.125669","url":null,"abstract":"<div><h3>Background</h3><div>Nanotechnology-based drug delivery systems, such as solid lipid nanoparticles (SLNs), offer promising strategies to enhance the efficacy and stability of therapeutic agents. In this study, we explored the characterization, stability, and therapeutic efficacy of SLNs loaded with Combretastatin A4 (CA4) in cancer treatment.</div></div><div><h3>Methods</h3><div>SLNs loaded with CA4 were characterized for particle size, zeta potential, and encapsulation efficiency. The stability of CA4 SLNs was assessed over six months. The MTT assay was used to evaluate the cytotoxicity of free CA4 and SLNs loaded with CA4 on C26 mouse colon carcinoma cells and HUVEC human umbilical vein endothelial cells. The anti-angiogenic activity was analyzed using the CAM assay. An <em>in vivo</em> study was conducted to assess the therapeutic efficacy of SLNs loaded with CA4 in combination with Doxil in a mouse tumor model.</div></div><div><h3>Results</h3><div>Blank SLNs and SLNs loaded with CA4 exhibited a homogeneous particle size distribution (60–70 nm and 80–90 nm, respectively), low polydispersity index, and a negative zeta potential. Encapsulation efficiency of CA4 was around 60 %. SLNs demonstrated excellent physicochemical stability over six months. The MTT assay revealed enhanced cytotoxicity of SLNs loaded with CA4 compared to free CA4, particularly in C26 cells. The CAM assay showed a concentration-dependent reduction in vessel density with CA4 treatment. In <em>in vivo</em> studies, SLNs loaded with CA4 significantly inhibited tumor growth and improved survival rates, especially when combined with Doxil.</div></div><div><h3>Conclusion</h3><div>These findings suggest that SLNs loaded with CA4 could be a valuable strategy for enhancing therapeutic outcomes in cancer treatment.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"678 ","pages":"Article 125669"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918165","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

Lipidized LL37-loaded PLGA nanocarriers: Bioengineered peptide delivery systems for enhanced wound healing 脂化ll37负载PLGA纳米载体：用于增强伤口愈合的生物工程肽递送系统

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-04-30 DOI: 10.1016/j.ijpharm.2025.125668

Chiara De Soricellis , Chloé Laigle , Lucio Spinelli , Maria Chiara Monti , Chiara Amante , Paola Russo , Rita Patrizia Aquino , Patricia Rousselle , Giovanna Lollo , Pasquale Del Gaudio

{"title":"Lipidized LL37-loaded PLGA nanocarriers: Bioengineered peptide delivery systems for enhanced wound healing","authors":"Chiara De Soricellis , Chloé Laigle , Lucio Spinelli , Maria Chiara Monti , Chiara Amante , Paola Russo , Rita Patrizia Aquino , Patricia Rousselle , Giovanna Lollo , Pasquale Del Gaudio","doi":"10.1016/j.ijpharm.2025.125668","DOIUrl":"10.1016/j.ijpharm.2025.125668","url":null,"abstract":"<div><div>Antimicrobial peptides (AMPs) such as LL37 offer a promising alternative to conventional antibiotics in treating chronic and multidrug-resistant wound infections. However, their clinical translation is limited by rapid degradation and cytotoxicity at high concentrations. This study investigates the encapsulation of a palmitoylated LL37 in a FDA-approved poly(lactic-co-glycolic acid) (PLGA) nanoparticles using two fabrication techniques, nanoprecipitation and microfluidics, to enhance stability and controlled peptide release. Microfluidic-generated nanoparticles demonstrated superior size uniformity, smaller hydrodynamic size (102.3 ± 2.0 nm vs 189.3 ± 3.4 nm), improved stability, and prolonged LL37(P) release compared to nanoparticles obtained via bulk nanoprecipitation method. LL37-encapsulated nanoparticles demonstrated controlled peptide release, enhanced keratinocyte uptake, and significant fibroblast-mediated wound closure acceleration. Proteomic analysis of the nanoparticle-protein corona revealed enrichment in proteins involved in coagulation, inflammation modulation, and extracellular matrix remodelling, suggesting an active role of nanoparticles in modulating the wound healing microenvironment. These findings highlight PLGA-based LL37 loaded nanocarriers as a promising biopolymer platform for AMP delivery in wound healing applications and as a viable therapeutic strategy in regenerative medicine and infection control.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"677 ","pages":"Article 125668"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902574","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

Targeted delivery of circPDHK1 siRNA via aptamer functionalized lipid nanoparticles inhibits ccRCC growth and migration 通过适体功能化的脂质纳米颗粒靶向递送circPDHK1 siRNA可抑制ccRCC的生长和迁移

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-04-30 DOI: 10.1016/j.ijpharm.2025.125666

Hao Ning , Yan Jiang , Binbin Li , Junwu Ren , Ai Ran , Wei Li , Bin Xiao

{"title":"Targeted delivery of circPDHK1 siRNA via aptamer functionalized lipid nanoparticles inhibits ccRCC growth and migration","authors":"Hao Ning , Yan Jiang , Binbin Li , Junwu Ren , Ai Ran , Wei Li , Bin Xiao","doi":"10.1016/j.ijpharm.2025.125666","DOIUrl":"10.1016/j.ijpharm.2025.125666","url":null,"abstract":"<div><div>Clear Cell Renal Cell Carcinoma (ccRCC) is a common malignancy with high mortality in China, requiring innovative treatments. Recent advances in nucleic acid drugs, notably small interfering RNAs (siRNAs), show promise for therapeutic applications. Circular RNAs (circRNAs) play vital roles in cancer progression, and our previous work has identified that upregulated circPDHK1 can promote ccRCC growth and migration. However, the delivery strategies of si circPDHK1 targeting the circPDHK1 against ccRCC are not thoroughly investigated. Here, we developed a novel nucleic acid drug delivery system, AS1411/LNP-si circPDHK1, utilizing lipid nanoparticles (LNPs) encapsulated with siRNA targeting circPDHK1 and modified with the AS1411 aptamer for precise tumor targeting. <em>In vitro</em> and <em>in vivo</em> studies demonstrated that AS1411/LNP-si circPDHK1 efficiently delivered si circPDHK1 to ccRCC cells, resulting in a significant reduction in circPDHK1 expression. This delivery system exhibited superior tumor-targeting capabilities and prolonged circulation time compared with non-targeted formulations. Notably, AS1411/LNP-si circPDHK1 successfully inhibited the phosphorylation of the mTOR-AKT pathway, suppressed the proliferation and migration of ccRCC cells, and exhibited minimal side effects in vital organs. Taken together, the aptamer-guided LNP loaded siRNA targeting circPDHK1 (AS1411/LNP-si circPDHK1) displays great potential for ccRCC therapy.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"677 ","pages":"Article 125666"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902573","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