International Journal of Pharmaceutics最新文献

Quality by design-based optimization of teriflunomide and quercetin combinational topical transferosomes for the treatment of rheumatoid arthritis 基于设计的特立氟胺和槲皮素组合外用转移体的质量优化，用于治疗类风湿性关节炎

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2024-10-13 DOI: 10.1016/j.ijpharm.2024.124829

{"title":"Quality by design-based optimization of teriflunomide and quercetin combinational topical transferosomes for the treatment of rheumatoid arthritis","authors":"","doi":"10.1016/j.ijpharm.2024.124829","DOIUrl":"10.1016/j.ijpharm.2024.124829","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease. Combination therapy is anticipated to surpass monotherapy by targeting multiple pathways involved in RA progression. The present aim is to develop a combination of Teriflunomide (TFD) and Quercetin (QCN) loaded transferosomal gel to enhance permeability and achieve localized delivery to joint tissues. TFD or QCN transferosomes were optimized employing a 3-level, 3-factorial design Box-Behnken design (BBD). The transferosomes exhibited sustained <em>in-vitro</em> drug release. The topical combination gel underwent thorough evaluation of rheology, and also <em>ex-vivo</em> studies showed enhanced permeability through rat skin. The synergistic combination of TFD and QCN effectively suppressed NO, TNF-α and IL-6 levels in <em>in-vitro</em> RAW 264.7 cells. The cytotoxicity in HaCaT cell lines indicates non-toxicity of the gel, further confirmed by skin irritation study conducted in rats. The <em>in-vivo</em> anti-arthritic activity was evaluated in complete freund’s adjuvant induced rat paw edema model illustrates the effectiveness of the combination transferosomal gel compared to other treatment groups. In conclusion, the topical delivery of TFD and QCN combination transferosomal gel demonstrated anti-arthritic activity through localized delivery whichallows for dose reduction, thereby may reduce the systemic drug exposure and mitigate the side effects associated with oral administration of TFD.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440862","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

Nasal administration of Xingnaojing biomimetic nanoparticles for the treatment of ischemic stroke 治疗缺血性中风的鼻腔给药仿生纳米颗粒（Xingnaojing biomimetic nanoparticles

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2024-10-12 DOI: 10.1016/j.ijpharm.2024.124830

引用次数: 0

A manganese-oxide nano-rambutan as the intrinsic modifier for hypericin delivery and triple-negative breast cancer treatment 锰氧化物纳米拉姆丁作为金丝桃素输送和三阴性乳腺癌治疗的内在修饰剂

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2024-10-11 DOI: 10.1016/j.ijpharm.2024.124824

{"title":"A manganese-oxide nano-rambutan as the intrinsic modifier for hypericin delivery and triple-negative breast cancer treatment","authors":"","doi":"10.1016/j.ijpharm.2024.124824","DOIUrl":"10.1016/j.ijpharm.2024.124824","url":null,"abstract":"<div><div>The anti-tumor efficacy of naturally derived photosensitizer-hypericin (Hy) is dampened by hypoxia and over-expressed glutathione in the tumor microenvironment (TME). For rewiring the TME, we encapsulated Hy to an intrinsic modifier-manganese oxide-formed nanorambutan (MnO<sub>x</sub>-Hy NR). In triple-negative breast cancer cells, MnO<sub>x</sub>-Hy NR not only consumed glutathione through Mn<sup>2+</sup> and hypericin release but also facilitated O<sub>2</sub> production to relieve hypoxia, through which the reactive oxygen species (ROS) generation was strengthened by endoplasmic reticulum targeting hypericin. In the meantime, glutathione consumption-induced glutathione peroxidase 4 (GPX4) inactivation and the elevation of lipid hydroperoxide (LPO) level further triggered ferroptosis. Then, the combination of PDT and ferroptosis contributed to a synergic immunogenic cell death (ICD) effect in 4 T1 cells, facilitating the adaptive anti-tumor immune response activation. Thereby, MnO<sub>x</sub>-Hy NR exhibited excellent anti-tumor effects both in primary and distant tumors through the abscopal effect, as well as significant lung metastasis inhibition in the 4 T1 mouse metastatic tumor model.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440859","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

‘Exploring the preparation of griseofulvin CAMS with amino acids of different hydrophobicity as co-formers using a modified hot-melt extrusion process’ 探索使用改良热熔挤出工艺制备以不同疏水性氨基酸为共聚物的鬼臼毒素 CAMS"。

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2024-10-10 DOI: 10.1016/j.ijpharm.2024.124818

{"title":"‘Exploring the preparation of griseofulvin CAMS with amino acids of different hydrophobicity as co-formers using a modified hot-melt extrusion process’","authors":"","doi":"10.1016/j.ijpharm.2024.124818","DOIUrl":"10.1016/j.ijpharm.2024.124818","url":null,"abstract":"<div><div>Co-amorphous systems (CAMS) of griseofulvin (GRI) with the amino acids (AA): L-lysine (LYS), L-valine (VAL) and L-methionine (MET) of increasing hydrophobicity were prepared using a solvent assisted hot-melt extrusion (HME). Co-formability was evaluated by thermodynamic miscibility prediction, thermal analysis (DSC), powder crystallography (pXRD) and vibrational spectroscopy (ATR-FTIR). Decomposition temperature range was defined by thermogravimetry (TGA) and DSC. Solubilities of crystalline and amorphous drug were determined by the UV-extinction method. The physical stability of GRI/AA CAMS was evaluated by accelerated tests and for ratios 1:1 and 1:2 was excellent. Non-sink dissolution tests of equimolar CAMS of the more hydrophobic MET and VAL revealed long lasting supersaturation, above the solubility of amorphous drug, whereas ratios 2:1 and 1:2 gave lower supersaturation due to partial recrystallization during dissolution, despite the good physical stability. CAMS of the hydrophilic LYS were physically stable but showed poor dissolution, possibly due to self-association of LYS in water. Addition of wetting agent in the dissolution medium improved dissolution without altering the profile. Since previous attempts to formulate GRI/AA CAMS with purely mechanical methods found only moderate success, the feed pretreatment HME method employed in this work makes an excellent alternative for drug/AA CAMS where mechanical or solvent evaporation methods fail.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406380","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

WaSPred: A reliable AI-based water solubility predictor for small molecules WaSPred：基于人工智能的可靠小分子水溶性预测器。

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2024-10-09 DOI: 10.1016/j.ijpharm.2024.124817

{"title":"WaSPred: A reliable AI-based water solubility predictor for small molecules","authors":"","doi":"10.1016/j.ijpharm.2024.124817","DOIUrl":"10.1016/j.ijpharm.2024.124817","url":null,"abstract":"<div><div>A rapid and reliable evaluation of the aqueous solubility of small molecules is a hot topic for the scientific community and represents a field of particular interest in drug discovery. In fact, aqueous solubility significantly impacts various aspects that collectively influence a drug’s overall pharmacokinetics, including absorption, distribution and metabolism. For this reason, <em>in silico</em> approaches that provide fast and cost-effective solubility predictions, can serve as invaluable tools in the early stages of drug development. Although additional molecular features should be considered, accurate solubility predictions can help medicinal chemists rationally planning the synthesis of compounds more likely to exhibit desirable pharmacokinetic properties and in selecting the most promising candidates for further biological testing (e.g., cellular assays) from an initial pool of hit compounds with detected preliminary bioactivity. In this context, we herein report the development and evaluation of WaSPred, our AI-based water solubility predictor for small molecules. WaSPred not only showed high reliability in water solubility predictions performed on structurally heterogeneous compounds, belonging to multiple external datasets, but also demonstrated superior performance compared to a set of other commonly used water solubility predictors, thus confirming its state-of the-art robustness and its usefulness as an <em>in silico</em> approach for water solubility evaluations..</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400236","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

Dihydroquercetin nanoparticles nasal gel is a promising formulation for amelioration of Alzheimer’s disease 二氢槲皮素纳米颗粒鼻腔凝胶是一种有望改善阿尔茨海默病的配方。

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2024-10-09 DOI: 10.1016/j.ijpharm.2024.124814

{"title":"Dihydroquercetin nanoparticles nasal gel is a promising formulation for amelioration of Alzheimer’s disease","authors":"","doi":"10.1016/j.ijpharm.2024.124814","DOIUrl":"10.1016/j.ijpharm.2024.124814","url":null,"abstract":"<div><div>Dihydroquercetin is a natural flavonoid with anti-inflammatory, antioxidant, and neuroprotective activities. Dihydroquercetin exhibits a great neuroprotector promise in Alzheimer’s disorder via preventing the aggregation of amyloid-beta-peptide-Aβ(1–42). The goal of the study was to create dihydroquercetin-loaded-chitosan nanoparticles (DHQ-CS NPs) loaded to a mucoadhesive, thermosensitive in-situ gel for direct nasal administration to cure Alzheimer’s disorder. Loading drug in chitosan nanoparticles and incorporation into thermosensitive gel enhanced residence time and reduced mucociliary-clearance. Different in-vitro-physicochemical-characteristics of gels and nanoparticles-characterization were used to evaluate the formulations. The therapeutic effectiveness of DHQ-CS NPs gel was evaluated behaviorally, biochemically and histopathologically in Alzheimer’s-rat-model compared to intranasal DHQ gel. The small particles-size was obtained = 235.3 nm of DHQ-CS NPs. The DHQ-CS NPs gel demonstrated a greater release rate compared to the raw DHQ gel. Additionally, the nasal-administration of the DHQ-CS NPs gel showed better In-vivo results compared to DHQ gel, through improvement of memory and learning deficits and also the exploratory behavior and new object memory in streptozotocin induced-Alzheimer rats. Biochemically, the intranasal DHQ-CS NPs gel, showed reduced both Aβ-protein formation and tau protein hyperphosphorylation, inhibition of acetylcholine esterase activity and oxidative stress in the brain with increase of total antioxidants in the brain and serum, compared to DHQ gel. Histopathologically, the DHQ-CS NPs nasal gel produced improvement in the hippocampal and cerebral cortex structures, being comparable to the normal group. Consequently, the intranasal DHQ-CS NPs loaded in-situ gel seems to be a promising therapeutic formulation for Alzheimer’s disease medication.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390469","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

Exploiting inhalable microparticles incorporating hybrid polymer-lipid nanoparticles loaded with Iloprost manages lung hyper-inflammation 利用含有伊洛前列素的混合聚合物-脂质纳米吸入微粒治疗肺部炎症。

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2024-10-09 DOI: 10.1016/j.ijpharm.2024.124813

{"title":"Exploiting inhalable microparticles incorporating hybrid polymer-lipid nanoparticles loaded with Iloprost manages lung hyper-inflammation","authors":"","doi":"10.1016/j.ijpharm.2024.124813","DOIUrl":"10.1016/j.ijpharm.2024.124813","url":null,"abstract":"<div><div>This study focuses on developing of a novel inhalation therapy for managing lung hyper-inflammation, producing hybrid polymer-lipid nanoparticles loaded with Iloprost (Ilo). These nanoparticles showed a size of approximately 100 nm with a core–shell structure and provided prolonged drug release, reaching 28 wt% after 6 h of incubation. The phospholipid composition and quantity (64 wt% on the total sample weight) result in minimal interaction with mucin and a significant effect on the rheology of a cystic fibrosis mucus model, in terms of reducing complex viscosity.</div><div>To obtain an inhalable microparticulate matrix suitable for incorporating Ilo@PEG-LPHNPs, the qualitative and quantitative composition of the feed fluid for the spray drying (SD) process was optimized. The selected composition (10 % wt/vol of mannitol and 10 % wt of ammonium bicarbonate relative to the weight of mannitol) was used to produce Nano-into Microparticles (NiM). The characterization of NiM revealed excellent aerodynamic properties, with a Mass Median Aerodynamic Diameter (MMAD) of 4.34 μm and a Fine Particle Fraction (FPF) of approximately 57 %. Biological characterization revealed that the particles are non-toxic to 16-HBE cells and can effectively evade macrophage uptake, likely due to the presence of PEG in their composition. Moreover, the delivered Iloprost significantly downregulates the production of the pro-inflammatory cytokine IL-6, showing the therapeutic potential of this drug delivery system.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390470","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

Preparation and evaluation of novel oral tacrolimus nanocochleates for organ transplantation to reduce individual differences and improve drug safety 制备和评估用于器官移植的新型口服他克莫司纳米絮凝物，以减少个体差异并提高药物安全性。

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2024-10-09 DOI: 10.1016/j.ijpharm.2024.124811

{"title":"Preparation and evaluation of novel oral tacrolimus nanocochleates for organ transplantation to reduce individual differences and improve drug safety","authors":"","doi":"10.1016/j.ijpharm.2024.124811","DOIUrl":"10.1016/j.ijpharm.2024.124811","url":null,"abstract":"<div><div>After organ transplantation, patients require treatment with immunosuppressive drugs to prevent immune rejection and transplantation failure. Tacrolimus (FK506) is a widely used immunosuppressant known for its potent immunosuppressive effect and narrow therapeutic range. Monitoring of FK506 blood concentrations is essential to avoid nephrotoxicity. In this study, a novel FK506 nanomedicine (FK506 cochleates) was developed using a microfluidic method to reduce variability among individuals and improve drug safety. The particle size of FK506 cochleates was (183.3 ± 1.4) nm, the zeta potential was −(39.28 ± 2.12) mV, and the encapsulation efficiency was more than 85 %. Particle size of FK506 cochleates could be maintained for up to 12 weeks in freeze-dried powder form. Small-angle X-ray scattering (SAXS) experiment confirmed the formation of cochleates by adding calcium solution. <em>In vitro</em> release studies demonstrated a sustained-release profile of FK506 from the cochleates carrier. Furthermore, the cochleates carrier could protect FK506 from the influence of stomach acid and slowly release the drug in the intestine. After oral administration, FK506 cochleates exhibited sustained-release properties in rats, accumulating in the spleen and lymph nodes − key anatomical sites for FK506’s pharmacological action. Importantly, FK506 cochleates significantly prolonged the survival time in the rabbit heart transplantation model while maintaining good safety profiles. In conclusion, the FK506 cochleates showed promising potential for enhancing drug safety in therapeutic organ transplantation.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390485","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

Dr. Paul W. S. Heng, a guru in pharmaceutical processing research 药物加工研究大师 Paul W. S. Heng 博士。

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2024-10-09 DOI: 10.1016/j.ijpharm.2024.124816

引用次数: 0

Nano-strategies for advancing oral drug delivery: Porous silicon particles and cyclodextrin encapsulation for enhanced dissolution of poorly soluble drugs. 推进口服给药的纳米战略：多孔硅颗粒和环糊精包封技术促进难溶性药物的溶解。

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2024-10-07 DOI: 10.1016/j.ijpharm.2024.124809

Hennie Marie Johnsen, Werner Filtvedt, Jo Klaveness, Marianne Hiorth

{"title":"Nano-strategies for advancing oral drug delivery: Porous silicon particles and cyclodextrin encapsulation for enhanced dissolution of poorly soluble drugs.","authors":"Hennie Marie Johnsen, Werner Filtvedt, Jo Klaveness, Marianne Hiorth","doi":"10.1016/j.ijpharm.2024.124809","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2024.124809","url":null,"abstract":"<p><p>Development of novel active pharmaceutical ingredients (API) for oral use often face challenges due to low bioavailability. Nanoparticle-based drug delivery systems and cyclodextrin (CD) encapsulation offer promising solutions by enhancing API solubility or dissolution rates. Porous silicon nanoparticles have shown potential to encapsulate APIs in their amorphous form within pores, improving dissolution rates compared to crystalline counterparts. A novel synthesis approach, circumventing the expensive and tedious Si wafer material synthesis, has been developed using centrifugal Chemical Vapor Deposition (cCVD). Herein, various cCVD Si particles were evaluated for their ability to enhance the dissolution rate of the model drugs celecoxib (CEL), phenytoin (PHT), griseofulvin (GRI), diclofenac (DCF), and naproxen (NAP). Our findings demonstrate increased dissolution rates of all tested APIs when formulated with cCVD Si particles, compared to free API in pH 7.4 or pH 2.0. Particle characteristics were largely retained after loading, and the solid state of the loaded APIs were evaluated using Differential Scanning Calorimetry (DSC). Dissolution kinetics were influenced by the particle properties, mass loading and API characteristics. Loading of CD-CEL, -GRI and -DCF complexes into the cCVD Si particles showed a potential for further enhanced dissolution rates, representing the first reported investigation of this combination. In conclusion, the cCVD Si particles are promising for improving the dissolution rate of poorly soluble drugs, potentially due to precipitation of amorphous or metastable forms. Further enhancements were observed upon loading CD-drug complexes, thereby offering promising strategies for optimizing drug bioavailability.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390472","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