Pharmaceutics最新文献

{"title":"Parenteral Nanoemulsion for Optimized Delivery of GL-II-73 to the Brain-Comparative In Vitro Blood-Brain Barrier and In Vivo Neuropharmacokinetic Evaluation.","authors":"Kristina Jezdić, Jelena Đoković, Ivan Jančić, Tanja Ilić, Biljana Bufan, Bojan Marković, Jana Ivanović, Tijana Stanković, Nebojša D Cekić, Vassiliki Papadimitriou, Dishary Sharmin, Prithu Mondal, James M Cook, Snežana D Savić, Miroslav M Savić","doi":"10.3390/pharmaceutics17030354","DOIUrl":"10.3390/pharmaceutics17030354","url":null,"abstract":"<p><p><b>Background/Objectives</b>: GL-II-73 is a positive allosteric modulator that is selective for α5GABA_A receptors and has physicochemical properties that favor nanocarrier formulations when parenteral delivery to the central nervous system is desired. Our aim was to develop an optimized nanoemulsion containing GL-II-73 and subsequently test whether this would improve permeation across the blood-brain barrier (BBB) and availability in the brain. <b>Methods</b>: The nanoemulsions were formulated and subjected to detailed physiochemical characterization. The optimized formulation was tested in comparison to a solution of GL-II-73 in the appropriate solvent in an in vitro model of the blood-brain barrier based on human induced pluripotent stem cell-derived microvascular endothelial cells, astrocytes, and pericytes. Plasma and brain exposure to GL-II-73 and its metabolite MP-III-022 was investigated in an in vivo neuropharmacokinetic study in rats exposed to the selected nanoemulsion and the conventional solution formulation. <b>Results</b>: The selected biocompatible nanoemulsion exhibited satisfactory physicochemical properties for parenteral administration, with a Z-ave of 122.0 ± 1.5, PDI of 0.123 ± 0.009 and zeta potential of -40.7 ± 1.5, pH of 5.16 ± 0.04, and adequate stability after one year of storage, and allowed the localization of GL-II-73 in the stabilization layer. The permeability of GL-II-73 through the BBB was twice as high with the selected nanoemulsion as with the solution. The availability of GL-II-73 and MP-III-022 (also a positive allosteric modulator selective for α5GABA_A receptors) in the brain was 24% and 61% higher, respectively, after intraperitoneal administration of the nanoemulsion compared to the solution; the former increase was statistically significant. <b>Conclusions</b>: The increased permeability in vitro proved to be a good predictor for the improved availability of GL-II-73 in brain tissue in vivo from the formulation obtained by encapsulation in a nanoemulsion. The putative additive effect of the parent molecule and its metabolite MP-III-022 could lead to enhanced and/or prolonged modulation of α5GABA_A receptors in the brain.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Green Synthesis of Silver Nanoparticles Using <i>Paullinia cupana</i> Kunth Leaf Extract Collected in Different Seasons: Biological Studies and Catalytic Properties.","authors":"Alan Kelbis Oliveira Lima, Ítalo Rennan Sousa Vieira, Lucas Marcelino Dos Santos Souza, Isadora Florêncio, Ingrid Gracielle Martins da Silva, Alberto Gomes Tavares Junior, Yasmin Alves Aires Machado, Lucas Carvalho Dos Santos, Paulo Sérgio Taube, Gerson Nakazato, Laila Salmen Espindola, Lorena Carneiro Albernaz, Klinger Antônio da França Rodrigues, Marlus Chorilli, Hugo de Campos Braga, Dayane Batista Tada, Sônia Nair Báo, Luís Alexandre Muehlmann, Mônica Pereira Garcia","doi":"10.3390/pharmaceutics17030356","DOIUrl":"10.3390/pharmaceutics17030356","url":null,"abstract":"<p><p><b>Background:</b><i>Paullinia cupana</i> Kunth, popularly known as guarana, a native Amazonian shrub cultivated by the Sateré-Mawé ethnic group, has been used in traditional medicine for various purposes, including stimulant and therapeutic actions, due to its chemical composition, which is rich in bioactive compounds. This study explored the reductive potential of guarana with nanobiotechnology and aimed to synthesize silver nanoparticles (AgNPs) using the aqueous extract of leaves collected during the dry and rainy seasons, assessing their biological and catalytic activities. <b>Methods:</b> The AgNPs were synthesized in a water bath at 70 °C for three hours and then characterized using techniques such as UV-Vis spectroscopy, DLS, zeta potential, MET, NTA, and EDX and had their effects on various biological systems assessed in vitro, as well as in catalytic tests aimed at indicating the probable influence of the time when the plant material was collected on the properties of the nanostructures. <b>Results:</b> The AgNPs had an average diameter between 39.33 and 126.2 nm, spherical morphology, absorption bands between 410 and 450 nm, and high colloidal stability over two years. The biological results showed antibacterial activity against all the species tested, as well as remarkable antioxidant action against DPPH and ABTS free radicals, in the same way as the aqueous leaf extracts of <i>P. cupana</i>, in addition to cytotoxic properties against cancerous (A431 and A549) and non-cancerous (HaCaT and HNTMC) cells. The AgNPs were active against promastigote forms of <i>Leishmania (Leishmania) amazonensis</i> while not affecting the viability of macrophages, and from the LC₅₀ and LC₉₀ values, the AgNPs were more effective than the metal salt solution in controlling <i>Aedes aegypti</i> larvae and pupae. We also reported that the catalytic degradation of the organic dyes methylene blue (MB) and methyl orange (MO) by AgNPs was over 90% after 40 or 14 min, respectively. <b>Conclusions:</b> Thus, our results support the potential of seasonal extracts of guarana leaves to produce AgNPs with diverse application possibilities for the health, industrial, and environmental sectors.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Albumin-Based Nanoparticles with Factorial Design as a Promising Approach for Remodeled Repaglinide: Evidence from In Silico, In Vitro, and In Vivo Evaluations.","authors":"Mennatullah M Faisal, Eman Gomaa, Mohamed S Attia, Rana M Abdelnaby, Adel Ehab Ibrahim, Ahmed Al-Harrasi, Sami El Deeb, Al Zahraa G Al Ashmawy","doi":"10.3390/pharmaceutics17030350","DOIUrl":"10.3390/pharmaceutics17030350","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Hyperlipidemia is a silent threat lurking in the bloodstream of millions worldwide. The nano-based platform has emerged as a promising drug delivery technology. Repaglinide, an anti-diabetic drug, was investigated recently as an antihyperlipidemic candidate that could supersede the available antihyperlipidemic drugs. Our goal was to optimize albumin-based nanoparticles loaded with Repaglinide for parenteral delivery and conduct in silico and in vivo studies to explore the efficacy of Repaglinide for the management of hyperlipidemia along with its anti-diabetic effect. <b>Methods:</b> The impact of three independent factors, the albumin%, acetone volume, and glutaraldehyde/albumin, on the particle size, zeta potential, and entrapment efficiency was investigated. <b>Results:</b> The optimized formulation was spherical, homogenous of an average diameter (~181.86 nm) with a narrow size distribution, a zeta potential of -24.26 mV, and 76.37% as the EE%. The in vitro release of Repaglinide from nanoparticles showed a sustained release pattern for 168 h, with an initial burst release after 24 h, and was fitted to the Fickian diffusion mechanism. A molecular docking simulation showed a strong affinity to several protein targets, and the results were very promising, where Repaglinide gave a score of -7.70 Kcal/mol compared to Mevastatin (-6.71 Kcal/mol) and Atorvastatin (-8.36 Kcal/mol). On conducting in vivo studies on animal models, the optimized formula recorded a statistically significant decrease in the serum levels of total cholesterol, triglyceride, and low-density lipoproteins, with an increased high-density lipoprotein. <b>Conclusions:</b> This study suggested albumin nanoparticles as potential nanocarriers for the parenteral delivery of Repaglinide to ameliorate its antihyperlipidemic benefits, especially in diabetic patients.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling Shear-Thinning Flow in Twin-Screw Extrusion Processes.","authors":"Vincent Kimmel, Lorena Gräfe, Luca Grieser, Alexey Lips, Robert Hennig, Judith Winck, Markus Thommes","doi":"10.3390/pharmaceutics17030353","DOIUrl":"10.3390/pharmaceutics17030353","url":null,"abstract":"<p><p><b>Background/Objective:</b> Hot-melt extrusion has been established as a formulation strategy for various pharmaceutical applications. However, tailoring the screw configuration is a major challenge where 1D modeling is utilized. This usually requires specific screw parameters, which are rarely noted in the literature, especially when dealing with shear-thinning formulations. <b>Methods:</b> Therefore, a custom-made test rig was used to assess the behavior of various conveying and kneading elements using Newtonian silicon oil and shear-thinning silicon rubber. The pressure and the power were measured as a function of volume flow. A model was proposed characterizing the screw element behavior by six individual parameters A1, A2, A3, B1, B2, B3. <b>Results:</b> The experimental results regarding the behavior with respect to Newtonian fluids were in good agreement with the literature and were modeled in accordance with the Pawlowski approach. In terms of shear-thinning fluids, the influence of screw speed on pressure and power was quantified. An evaluation framework was proposed to assess this effect using two additional parameters. Based on a high number of repetitive measurements, a confidence interval for the individual screw parameters was determined that is suitable to highlight the differences between element types. <b>Conclusions:</b> Finally, geometrical screw parameters for Newtonian and shear-thinning flow were assessed and modeled, with three conveying and three kneading elements characterized.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmaceutical 3D Printing Technology Integrating Nanomaterials and Nanodevices for Precision Neurological Therapies.","authors":"Jurga Bernatoniene, Mindaugas Plieskis, Kestutis Petrikonis","doi":"10.3390/pharmaceutics17030352","DOIUrl":"10.3390/pharmaceutics17030352","url":null,"abstract":"<p><p>Pharmaceutical 3D printing, combined with nanomaterials and nanodevices, presents a transformative approach to precision medicine for treating neurological diseases. This technology enables the creation of tailored dosage forms with controlled release profiles, enhancing drug delivery across the blood-brain barrier (BBB). The integration of nanoparticles, such as poly lactic-co-glycolic acid (PLGA), chitosan, and metallic nanomaterials, into 3D-printed scaffolds improves treatment efficacy by providing targeted and prolonged drug release. Recent advances have demonstrated the potential of these systems in treating conditions like Parkinson's disease, epilepsy, and brain tumors. Moreover, 3D printing allows for multi-drug combinations and personalized formulations that adapt to individual patient needs. Novel drug delivery approaches, including stimuli-responsive systems, on-demand dosing, and theragnostics, provide new possibilities for the real-time monitoring and treatment of neurological disorders. Despite these innovations, challenges remain in terms of scalability, regulatory approval, and long-term safety. The future perspectives of this technology suggest its potential to revolutionize neurological treatments by offering patient-specific therapies, improved drug penetration, and enhanced treatment outcomes. This review discusses the current state, applications, and transformative potential of 3D printing and nanotechnology in neurological treatment, highlighting the need for further research to overcome the existing challenges.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chondroitin Sulfate-Based Imatinib Nanoparticles Targeting Activated Hepatic Stellate Cells Against Hepatic Fibrosis.","authors":"Xunzhi Liu, Changlong Fang, Hongling Yu, Lu Huang, Jiaxing Feng, Shiqin Luo, Li Song, Mengying Wu, Yulu Tan, Jianxia Dong, Tao Gong, Peihong Xiao","doi":"10.3390/pharmaceutics17030351","DOIUrl":"10.3390/pharmaceutics17030351","url":null,"abstract":"<p><p><b>Background</b>: Activated hepatic stellate cells (aHSCs) play a significant role during the onset of hepatic fibrosis, ultimately leading to excessive deposition of extracellular matrix (ECM) and other typical pathological features, and thus have become a popular target for the treatment of hepatic fibrosis. However, current aHSC-centric therapy strategies achieve unsatisfactory results, mainly due to the lack of approved anti-fibrosis drugs and sufficiently efficient aHSC-targeted delivery systems. In this study, our aim was to develop an Imatinib-loaded nanoparticle delivery system based on a chondroitin sulfate derivative to enhance aHSC targeting efficiency, improve the therapeutic effect for hepatic fibrosis, and investigate the underlying mechanism. <b>Methods</b>: The carboxyl group of chondroitin sulfate and the amino group of 1-hexadecylamine were linked by an amide bond in this study to produce the amphiphilic carrier CS-HDA. Then, the Imatinib-loaded nanoparticles (IM-CS NPs) were designed to efficiently target aHSCs through CD44-mediated endocytosis and effectively inhibit HSC overactivation via PDGF and TGF-β signaling pathways. <b>Results</b>: Both in vitro cellular uptake experiments and in vivo distribution experiments demonstrated that CS-HDA-modified nanoparticles (IM-CS NPs) exhibited a better targeting ability for aHSCs, which were subsequently utilized to treat carbon tetrachloride-induced hepatic fibrosis mouse models. Finally, significant fibrosis resolution was observed in the carbon tetrachloride-induced hepatic fibrosis mouse models after tail vein injection of the IM-CS NPs, along with their outstanding biocompatibility and biological safety. <b>Conclusions</b>: IM-loaded NPs based on an amphiphilic CS derivative have remarkable antifibrotic effects, providing a promising avenue for the clinical treatment of advanced hepatic fibrosis.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative Hydrocortisone Acetate and Pramoxine Hydrochloride Topical Cream Formulations for Anorectal Conditions: Enhanced In Vitro Release Profile.","authors":"Onur Pinarbasli, Nurdan Atilgan, Ezgi Turkes, Nagehan Sarracoglu, Asuman Aybey Doganay","doi":"10.3390/pharmaceutics17030348","DOIUrl":"10.3390/pharmaceutics17030348","url":null,"abstract":"<p><p>This study focuses on analyzing the in vitro release characteristics, as well as improving the penetration rate and stability of hydrocortisone acetate and pramoxine. This medication combination (hydrocortisone and pramoxine) is the first generic drug product utilized to alleviate minor pain, itching, swelling, and discomfort associated with anorectal conditions such as hemorrhoids. <b>Background/Objectives</b>: The developed novel formulations contain hydrocortisone acetate and pramoxine HCl as active ingredients, at least one solvent, at least one penetrating agent, at least one emulsifying agent, at least one surfactant, and at least one antimicrobial preservative, and pH values between 3.0 and 5.0, preferably between 3.5 and 4.5. <b>Methods</b>: Typical semi-solid dosage form quality control tests included appearance, identification, content homogeneity, pH, viscosity, assay, compounds of interest, microbiological testing, and in vitro release testing. In in vitro release testing, a series of formulations containing hydrocortisone acetate and pramoxine were tested for in vitro release across the Strat-M membrane using Franz diffusion cells methodology in comparison to a reference product (Pramosone Cream 2.5%). <b>Results</b>: Quantitative content of the release tests of the active ingredients in the cream, assay tests, antimicrobial preservative efficacy, and stability tests were carried out by high-sensitivity liquid chromatography. <b>Conclusions:</b> In conclusion, the cream formulations developed in this study have the potential to offer more effective treatment compared to reference products in terms of both in vitro release rates, and their reliability and validity were confirmed through validation studies.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Development of Local Antiviral Formulations with Potent Virucidal Activity Against SARS-CoV-2 and Influenza Viruses.","authors":"Juthaporn Ponphaiboon, Wantanwa Krongrawa, Sontaya Limmatvapirat, Sukannika Tubtimsri, Akanitt Jittmittraphap, Pornsawan Leaungwutiwong, Chulabhorn Mahidol, Somsak Ruchirawat, Prasat Kittakoop, Chutima Limmatvapirat","doi":"10.3390/pharmaceutics17030349","DOIUrl":"10.3390/pharmaceutics17030349","url":null,"abstract":"<p><p><b>Background/Object:</b> This study investigates the in vitro antiviral potential of D-limonene (DLM), monolaurin (ML), and cetylpyridinium chloride (CPC) in formulations targeting SARS-CoV-2 and influenza viruses. The aim was to develop oral and nasal formulations with optimized concentrations of these active ingredients to evaluate their efficacy, safety, and stability. <b>Methods:</b> Oral (formulation D) and nasal (formulation E) products were developed using specific concentrations of DLM (0.2-0.3% <i>w</i>/<i>w</i>), ML (0.1-0.2% <i>w</i>/<i>w</i>), and CPC (0.05-0.075% <i>w</i>/<i>w</i>). In vitro virucidal activity assays were conducted to assess the antiviral efficacy of the formulations against SARS-CoV-2 and influenza viruses. Stability testing was also performed under various storage conditions. <b>Results:</b> Formulation D (0.3% <i>w</i>/<i>w</i> DLM, 0.2% <i>w</i>/<i>w</i> ML, 0.05% <i>w</i>/<i>w</i> CPC, and 1.5% <i>w</i>/<i>w</i> Cremophor RH40) demonstrated a 3.875 ± 0.1021 log reduction and 99.99 ± 0.0032% efficacy against SARS-CoV-2 within 120 s. Formulation E (0.2% <i>w</i>/<i>w</i> DLM, 0.05% <i>w</i>/<i>w</i> CPC, and 0.75% <i>w</i>/<i>w</i> Cremophor RH40) showed a 2.9063 ± 0.1197 log reduction and 99.87 ± 0.0369% efficacy against SARS-CoV-2. Both formulations achieved >99.99% efficacy and log reductions exceeding 4.000 against various influenza strains. Stability testing confirmed optimal performance at 4 °C with no microbial contamination. <b>Conclusions:</b> The findings suggest that both formulations exhibit broad-spectrum antiviral activity against SARS-CoV-2 and influenza viruses in vitro. These results support their potential for further clinical evaluations and therapeutic applications, particularly in oral and nasal spray formulations.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intra-Arterial Super-Selective Delivery of Yttrium-90 for the Treatment of Recurrent Glioblastoma: In Silico Proof of Concept with Feasibility and Safety Analysis.","authors":"Giulia Paolani, Silvia Minosse, Silvia Strolin, Miriam Santoro, Noemi Pucci, Francesca Di Giuliano, Francesco Garaci, Letizia Oddo, Yosra Toumia, Eugenia Guida, Francesco Riccitelli, Giulia Perilli, Alessandra Vitaliti, Angelico Bedini, Susanna Dolci, Gaio Paradossi, Fabio Domenici, Valerio Da Ros, Lidia Strigari","doi":"10.3390/pharmaceutics17030345","DOIUrl":"10.3390/pharmaceutics17030345","url":null,"abstract":"<p><p><b>Background</b>: Intra-arterial cerebral infusion (IACI) of radiotherapeutics is a promising treatment for glioblastoma (GBM) recurrence. We investigated the in silico feasibility and safety of Yttrium-90-Poly(vinyl alcohol)-Microbubble (⁹⁰Y-PVA-MB) IACI in patients with recurrent GBM and compared the results with those of external beam radiation therapy (EBRT). <b>Methods</b>: Contrast-enhanced T1-weighted magnetic resonance imaging (T1W-MRI) was used to delineate the tumor volumes and CT scans were used to automatically segment the organs at risk in nine patients with recurrent GBM. Volumetric Modulated Arc Therapy (VMAT) treatment plans were generated using a clinical treatment planning system. Assuming the relative intensity of each voxel from the MR-T1W as a valid surrogate for the post-IACI ⁹⁰Y-PVA-MB distribution, a specific ⁹⁰Y dose voxel kernel was obtained through Monte Carlo (MC) simulations and convolved with the MRI, resulting in a ⁹⁰Y-PVA-MB-based dose distribution that was then compared with the VMAT plans. <b>Results</b>: The physical dose distribution obtained from the simulation of 1GBq of ⁹⁰Y-PVA-MBs was rescaled to ensure that 95% of the prescribed dose was delivered to 95% or 99% of the target (i.e., A95% and A99%, respectively). The calculated activities were A95% = 269.2 [63.6-2334.1] MBq and A99% = 370.6 [93.8-3315.2] MBq, while the mean doses to the target were 58.2 [58.0-60.0] Gy for VMAT, and 123.1 [106.9-153.9] Gy and 170.1 [145.9-223.8] Gy for A95% and A99%, respectively. Additionally, non-target brain tissue was spared in the ⁹⁰Y-PVA-MB treatment compared to the VMAT approach, with a median [range] of mean doses of 12.5 [12.0-23.0] Gy for VMAT, and 0.6 [0.2-1.0] Gy and 0.9 [0.3-1.5] Gy for the ⁹⁰Y treatments assuming A95% and A99%, respectively. <b>Conclusions</b>: ⁹⁰Y-PVA-MB IACI using MR-T1W appears to be feasible and safe, as it enables the delivery of higher doses to tumors and lower doses to non-target volumes compared to the VMAT approach.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of TGF-β3 and IL-1β on L-Type Voltage-Operated Calcium Channels and Calcium Ion Homeostasis in Osteoarthritic Chondrocytes and Human Bone Marrow-Derived Mesenchymal Stem Cells During Chondrogenesis.","authors":"Anastasiia Shelest, Aidas Alaburda, Raminta Vaiciuleviciute, Ilona Uzieliene, Paulina Bialaglovyte, Eiva Bernotiene","doi":"10.3390/pharmaceutics17030343","DOIUrl":"10.3390/pharmaceutics17030343","url":null,"abstract":"<p><p><b>Background:</b> Transforming growth factor-β (TGF-β) and interleukin 1β (IL-1β) are key regulators of the chondrogenic differentiation, physiology and pathology of cartilage tissue, with TGF-β promoting chondrogenesis and matrix formation, while IL-1β exerts catabolic effects, inhibiting chondrogenesis and contributing to cartilage degradation. Both cytokines alter the intracellular calcium ion (iCa²⁺) levels; however, the exact pathways are not known. <b>Objectives:</b> This study aimed to evaluate the impact of TGF-β3 and IL-1β on calcium homeostasis in human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and chondrocytes during chondrogenesis. <b>Results:</b> TGF-β3 increased iCa²⁺ levels in both hBM-MSCs and chondrocytes. Furthermore, TGF-β3 increased the functional activity of L-type voltage-operated calcium channels (L-VOCCs) in hBM-MSCs but not in chondrocytes. TGF-β3 and IL-1β reduced L-VOCCs subunit CaV1.2 (<i>CACNA1C</i>) gene expression in chondrocytes. In hBM-MSCs, TGF-β3 and IL-1β increased SERCA pump (<i>ATP2A2</i>) gene expression, while in chondrocytes, this effect was observed only with TGF-β3. <b>Conclusions:</b> TGF-β3 increases iCa²⁺ both in osteoarthritic chondrocytes and hBM-MSCs during chondrogenesis. In hBM-MSCs, TGF-β3-mediated elevation in iCa²⁺ is related to the increased functional activity of L-VOCCs. IL-1β does not change iCa²⁺ in osteoarthritic chondrocytes and hBM-MSCs; however, it initiates the mechanisms leading to further downregulation of iCa²⁺ in both types of cells. The differential and cell-specific roles of TGF-β3 and IL-1β in the calcium homeostasis of osteoarthritic chondrocytes and hBM-MSCs during chondrogenesis may provide a new insight into future strategies for cartilage repair and osteoarthritis treatment.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}