Tahmineh Karami, Mohammad Akrami, Ismaeil Haririan, Mohammad Mohammadi-Khanaposhti, Reza H Sajedi
{"title":"Pharmaceutical additive manufacturing of a pH-responsive core-shell tablet of beta-galactosidase to treat lactase intolerance.","authors":"Tahmineh Karami, Mohammad Akrami, Ismaeil Haririan, Mohammad Mohammadi-Khanaposhti, Reza H Sajedi","doi":"10.1007/s40199-025-00578-7","DOIUrl":"https://doi.org/10.1007/s40199-025-00578-7","url":null,"abstract":"<p><p>Lactose intolerance affects a significant portion of the global population. Among the proposed treatments for the disease, the main strategy is the use of Lactase, beta-galactosidase, and enzyme before consuming dairy products. The beta-galactosidase enzyme loses its activity in the acidic environment of the stomach before reaching the small intestine environment. In this study, a pH sensitive tablet of beta-galactosidase enzyme with local drug delivery was made for the treatment of lactose intolerance through the hydrogel formulation in the core compartment of the 3D-printed shell of the tablet. The tablets were characterized in terms of morphology, chemical interaction, mechanical properties, dissolution test and pharmacopeial physiochemical requirements. The best polymer weight percentages were selected during the 3D printing of the tablet so that less than 11% release of enzyme within 2 h inside the stomach environment (pH = 1.2) and about 100% enzyme release in the intestinal environment (pH = 6.8) within 6 h was achieved. It should be noted that the enzyme release was confirmed by SDS-PAGE. The recovery of the enzyme activity in tablet was 94%, compared to the activity of the free enzyme. SEM analysis showed smooth, uniform, and continuous layers and the results of FTIR analysis showed no covalent interactions between different materials in the manufacturing process. Furthermore, acceptable tolerances were obtained for pharmacopeial tests including weight variation, content uniformity and assay. According to the results, incorporation of hydrogel into melt extrusion-based 3D printing could be used for producing tailored tablets containing beta-galactosidase enzyme amounts with a delayed release formulation and local oral drug delivery to treat lactose intolerance.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"33 2","pages":"34"},"PeriodicalIF":2.1,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neda Moradloo, Samaneh Arab, Hamed Rezaee Jam, Samira Asgharzadeh, Saeed Shokri, Leila Nasehi, Ali Nokhodchi
{"title":"Effect of blueberry extract on enhancement of radiosensitivity in non-Hodgkin lymphoma by modulating proliferation and apoptosis.","authors":"Neda Moradloo, Samaneh Arab, Hamed Rezaee Jam, Samira Asgharzadeh, Saeed Shokri, Leila Nasehi, Ali Nokhodchi","doi":"10.1007/s40199-025-00577-8","DOIUrl":"10.1007/s40199-025-00577-8","url":null,"abstract":"<p><strong>Background: </strong>Non-Hodgkin lymphoma, a major cancer type, is usually treated with radiotherapy but encounters challenges with resistance and toxicity. Therefore, the treatment of non-Hodgkin lymphoma needs agents to be very effective while protecting healthy cells. Blueberry extract, rich in micronutrients, flavonoids, and bioactive compounds, may inhibit cancer cell growth and induce apoptosis without harming normal cells.</p><p><strong>Objectives: </strong>This study investigates the efficacy of blueberry extract in combination with radiotherapy as a radiosensitizer on Raji cells, a model for highly invasive non-Hodgkin lymphoma.</p><p><strong>Methods: </strong>First, Raji cells were treated with blueberry extract alone and in combination with a single dose of 2 Gy radiotherapy. The effects of blueberry extract on inhibiting proliferation and induction of apoptosis in Raji cells were investigated by MTT assay, flow cytometry (Annexin-V-FITC), cell cycle analysis, and quantitative gene expression analysis of BAX, BCL-2 and XPA. Its role in improving the efficacy of radiotherapy on cancer cells was also investigated.</p><p><strong>Results: </strong>Treated cells with blueberry extract alone and in combination with radiotherapy showed reduced viability, increased induction of apoptosis and a higher proportion of cells in the SUB-G1 cell cycle phase was detected. Additionally, gene expression analysis indicated upregulation of the pro-apoptotic gene BAX expression and decreased anti-apoptotic gene BCL-2 expression, along with elevated expression of XPA as an indicator of DNA damage after radiotherapy.</p><p><strong>Conclusion: </strong>The study suggests that blueberry extract stimulates apoptosis in Raji cells and could serve as an anti-cancer drug. Furthermore, the combination of this extract with radiotherapy could be used as a radiosensitizer.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"33 2","pages":"33"},"PeriodicalIF":2.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Innovative triamcinolone acetonide microsuspension for Non-Invasive ocular management of inflammation.","authors":"Forouhe Zahir-Jouzdani, Sepehr Ashrafi, Zahra Ghaemmaghamian, Bahar Kharazian, Saeed Shahbaz, Rasoul Dinarvand, Fatemeh Atyabi","doi":"10.1007/s40199-025-00576-9","DOIUrl":"10.1007/s40199-025-00576-9","url":null,"abstract":"<p><p>Enhancing the bioavailability of insoluble active agents in the eye through topical administration is a key focus in formulation science. This study aims to develop a microsuspension-based drug delivery system to effectively deliver anti-inflammatory drugs to deeper ocular tissues, offering a non-invasive alternative to intraocular injections.</p><p><strong>Methods: </strong>To improve the bioavailability of the hydrophobic drug triamcinolone acetonide (TA), we reduced its particle size using the wet ball milling method with zirconium oxide beads. To enhance mucus penetration, we coated the TA microsuspension with the non-ionic surfactant Poloxamer 407. The microsuspension was characterized for morphology, particle size, zeta potential, and dissolution properties in various ocular media. We also modeled TA distribution in different ocular compartments using GastroPlus™ software and evaluated the impact of formulation parameters such as particle size and viscosity.</p><p><strong>Results: </strong>Reducing the particle size to 250 nm significantly increased the dissolution rate of the microsuspension. The model indicated that viscosity and particle size are critical for enhancing the ocular concentration of eye drops in various tissues. Optimizing these parameters could lead to a nearly 40-fold reduction in the required TA eye drop dosage (from 4.0% w/v to 0.1% w/v).</p><p><strong>Conclusion: </strong>Our findings suggest that a TA formulation with a particle size of 1.0 μm or less and a viscosity of about 72.0 cp. can be as effective as a larger particle size formulation while delivering significantly higher TA concentrations. The enhanced uniformity, re-dispersibility, and improved distribution to ocular tissues position this microsuspension as a novel approach to overcoming ocular drug delivery challenges and reducing the need for intraocular injections.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"33 2","pages":"32"},"PeriodicalIF":2.1,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nuraziemah Ahmad, Mohmad Farooq Shaikh, Mohammed Tahir Ansari, Alina Arulsamy
{"title":"Nanoformulations in epilepsy therapy - a systematic review of emerging strategies in status epilepticus.","authors":"Nuraziemah Ahmad, Mohmad Farooq Shaikh, Mohammed Tahir Ansari, Alina Arulsamy","doi":"10.1007/s40199-025-00575-w","DOIUrl":"10.1007/s40199-025-00575-w","url":null,"abstract":"<p><p>Status epilepticus (SE) presents a life-threatening medical emergency condition characterized by prolonged seizures, leading to severe neuronal damage, morbidity and mortality, if not promptly treated. Immediate intervention is crucial, yet current anti-seizure medications (ASM) face limitations such as adverse effects otherwise in need of invasive administration routes such as intravenous ASMs. Nanoparticle-based drug delivery systems offer a promising approach to overcoming these challenges by enhancing drug solubility, stability, and brain bioavailability. This systematic review examines recent advancements in nanoformulations of ASMs for SE management. Through a comprehensive search and analysis of the literature, 12 relevant studies were identified, highlighting various nanoparticle types, formulation methods, and pharmacokinetic parameters. ASM nanoparticles exhibit favourable characteristics for drug delivery, including small size, high surface area, and tuneable physicochemical properties. These properties enable efficient drug transport across biological barriers, precise targeting, and controlled release, ultimately improving drug efficacy and reducing side effects. With an optimized release profile and non-invasive route such as intranasal administration, nano-formulated ASMs offer promising immediate therapeutic strategy for SE therapy. However, further research is warranted to optimize nano-formulation parameters, assess long-term safety, and validate clinical efficacy. Overall, nanoparticle-based ASM delivery holds great potential for revolutionizing SE treatment, offering hope for improved patient outcomes and quality of life.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"33 2","pages":"31"},"PeriodicalIF":2.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 evaluation of CeO<sub>2</sub> nanoparticles on doxorubicin induced cardiotoxicity: focused on oxidative stress, inflammation, apoptosis, and mitochondrial function.","authors":"Fahad Alsaikhan","doi":"10.1007/s40199-025-00573-y","DOIUrl":"10.1007/s40199-025-00573-y","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin (Dox) is a chemotherapy medication used in the therapy of cancers. However, despite its killing of cancer cells, Dox is toxic to the heart and can lead to heart failure. This outcome in turn poses a therapeutic challenge given the limited treatment options available to these individuals.</p><p><strong>Objectives: </strong>This study examines how CeO₂ nanoparticles, through oxidative stress, inflammation, apoptosis, and mitochondrial function, reduced Dox toxicity in human cardiac myocyte (HCM) cells.</p><p><strong>Methods: </strong>Following detection of the optimal doses of CeO₂ nanoparticles using the MTT assay, HCM cells were treated with Dox (8.25 µM) and CeO₂ nanoparticles for 24 h. Then, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) and the activity of superoxide dismutase (SOD) were determined. Furthermore, the mitochondrial membrane potential, mitochondrial swelling, and mitochondrial cytochrome c release were analyzed. The level of gene expression of IL-1β, IL-6, and TNF-α, as well as apoptosis, was also examined.</p><p><strong>Results: </strong>The data of this work demonstrated that Dox significantly elevated levels of ROS and MDA and reduced GSH level and SOD activity, which is modified by CeO₂ nanoparticles. Also, Dox meaningfully increased inflammation markers and apoptosis and induced mitochondrial malfunction, which were meaningfully reduced by CeO₂ nanoparticles in a dose-response manner in HCM cells.</p><p><strong>Conclusion: </strong>According to the present study results, CeO₂ nanoparticles, through a reduction in oxidative stress, inflammation, apoptosis, and mitochondrial malfunction, can have therapeutic potential in HCM cells toxicity induced by Dox.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"33 2","pages":"30"},"PeriodicalIF":2.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"New psychoactive substances: a multidisciplinary review of challenges and their diverse character.","authors":"Ilinca-Mihaela Marandiuc, Anca Oana Docea, Andreea Camelia Hîrjău, Oana Ruxandra Avram, Corina-Ștefania Matei, Aristidis Tsatsakis, Andreea-Letiția Arsene","doi":"10.1007/s40199-025-00572-z","DOIUrl":"10.1007/s40199-025-00572-z","url":null,"abstract":"<p><strong>Background: </strong>New psychoactive substances (NPS) pose a rapidly evolving public health challenge due to their diverse chemical structures and psychoactive effects, necessitating a comprehensive understanding of their classification, mechanisms of action, and detection.</p><p><strong>Objectives: </strong>Recognizing critical gaps in the understanding and management of NPS, this review aimed to synthesize current liter-ature. Specifically, we sought to elucidate the evolving classifications of NPS, delineate their underlying molecular mechanisms of action to inform therapeutic strategies, and critically evaluate existing detection methodologies to ad-dress current analytical limitations, thereby providing an essential, integrated perspective on this rapidly changing landscape.</p><p><strong>Methods: </strong>A narrative literature review was conducted to analyze NPS classification, molecular mechanisms, and detection techniques. Searches were performed across Web of Science, Scopus, PubMed, and Elsevier, using keywords such as \"synthetic cathinones\", \"designer drugs\", \"new psychoactive substance(s)\", \"detection of new psychoactive sub-stances\" and \"toxicology.\" Inclusion criteria prioritized studies primarily focused on NPS with clearly defined com-pounds (e.g., UNODC, EMCDDA classifications) and published within the last four years. Eligible publications en-compassed in vivo and in vitro studies, original research, and various review types. Exclusion criteria involved liter-ature outside the specified timeframe and studies on established drugs of abuse or licit substances, unless a direct comparative analysis with NPS was presented.</p><p><strong>Results: </strong>The review synthesized a classification framework for NPS, detailed the molecular mechanisms underlying their psychoactive effects, and summarized current detection methodologies. Furthermore, it underscored the significant health risks associated with NPS use, including addiction, psychological disturbances, organ toxicity, and fatal outcomes.</p><p><strong>Conclusion: </strong>The continued emergence and proliferation of NPS necessitate ongoing research to fully characterize their specific effects and associated risks. This review provides a foundational synthesis of current knowledge, not only supporting the development of evi-dence-based interventions to mitigate their public health impact, but also serving as a catalyst for new research direc-tions aimed at a deeper understanding and more effective management of these evolving compounds.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"33 2","pages":"29"},"PeriodicalIF":2.1,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12331572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Co-delivery of SN38 and rapamycin albumin bound nanoparticles against breast Cancer.","authors":"Sanaz Jamshidfar, Marzieh Ebrahimi, Reyhaneh Varshochian, Navid Goodarzi, Javad Firouzi, Mahsa Rezaei, Seyed Nasser Ostad, Yalda Hosseinzadeh Ardakani, Rassoul Dinarvand","doi":"10.1007/s40199-025-00569-8","DOIUrl":"10.1007/s40199-025-00569-8","url":null,"abstract":"<p><strong>Background: </strong>The co-delivery of two therapeutic agents within a single nanoparticle platform offers a potential strategy to improve treatment efficacy while minimizing adverse effects. Albumin as a biocompatible carrier could facilitate simultaneous delivery of cargos to the tumoral region based on passive targeting gained by enhanced permeability and retention (EPR).</p><p><strong>Objectives: </strong>This study aimed to develop, characterize, and assess a dual-drug delivery system incorporating rapamycin and SN38, utilizing the nanoparticle albumin bound technique, for the treatment of breast cancer.</p><p><strong>Methods: </strong>Albumin bound NPs of SN38 and rapamycin were prepared using probe sonication method. NPs were characterized using dynamic light scattering (DLS) and field emission scanning electron microscopy (FESEM) techniques to confirm their hydrodynamic diameter and structural properties. Drug loading (DL) and entrapment efficiency (EE) were measured using validated reverse phase high performance liquid chromatography (RP-HPLC) methods. Cellular cytotoxicity assay, cellular internalization, quantitatively cellular uptake, colony formation assay, and sphere formation assay were performed. To track NPs destiny as a 24 h follow up in the biodistribution part, NPs were intravenously injected to the BALB/c tumor bearing mice.</p><p><strong>Results: </strong>Blank NPs showed hydrodynamic diameter of about 121 nm, drug incorporation resulted in sizes around 200 nm. No toxicity was observed by MTT assay for blank albumin NPs. MTT assay of drug loaded NPs showed higher toxicity for dual drug loaded NPs compared to single drug loaded NPs. Confocal images and flow cytometry showed high accumulation of NPs in cytoplasmic space of 4T1 cells. All of the experimental groups showed significant decrease in colony formation and sphere formation in comparison to the control group. NPs were also preferentially accumulated in the tumoral region in vivo due to their suitable size.</p><p><strong>Conclusion: </strong>In conclusion, the designed drug delivery system proposes great potential for breast cancer treatment.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"33 2","pages":"26"},"PeriodicalIF":2.1,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12314136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maryam Shojaee, Mehdi Rostami, Mohammad Soukhtanloo, Mohammad Jalili-Nik
{"title":"Evaluation and comparison of the anti-proliferative and anti-metastatic effects of urolithin A and urolithin B against esophageal cancer cells: an in vitro and in silico study.","authors":"Maryam Shojaee, Mehdi Rostami, Mohammad Soukhtanloo, Mohammad Jalili-Nik","doi":"10.1007/s40199-025-00570-1","DOIUrl":"10.1007/s40199-025-00570-1","url":null,"abstract":"<p><strong>Introduction: </strong>Esophageal squamous cell carcinoma (ESCC) is a prevalent and lethal cancer, with traditional treatments often ineffective. This study investigates the anti-proliferative and anti-metastatic effects of natural compounds Urolithin A (UA) and Urolithin B (UB) on ESCC cell lines KYSE-30 and YM-1.</p><p><strong>Methods: </strong>KYSE-30 and YM-1 ESCC cells were treated with UA and UB, and their viability assays, cell cycle arrest, apoptosis, expressions of mRNA linked to apoptosis and metastasis, generation of reactive oxygen species (ROS), activity of MMP-2 and MMP-9, along with mRNA expressions of MMP-2 and MMP-9, and migration were assessed.</p><p><strong>Results: </strong>The results showed that UA (which had lower IC<sub>50</sub> than UB) and UB reduced the viability of both KYSE-30 and YM-1 cells. Furthermore, UA and UB exhibited lower toxicity towards normal HFF cells compared to ESCC cells. Both UB and the more effective UA induced apoptosis and caused G2/M cell cycle arrest in KYSE-30 and YM-1 cells. Additionally, UA and UB elevated ROS production and led to a decrease in Bcl-2 expression while increasing the expression of Bax and p21 genes. A decrease in the mRNA expression and enzymatic activity of MMP-2 and MMP-9 was observed following treatment with UA and UB.</p><p><strong>Conclusion: </strong>UB and, more potently, UA show the potential to induce apoptosis while reducing metastatic properties and migration of ESCC cells, suggesting them as promising candidates for new anti-ESCC therapies; however, further preclinical and clinical research is needed to fully understand their anti-cancer effects and mechanisms.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"33 2","pages":"28"},"PeriodicalIF":2.1,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12314155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 Fe<sub>3</sub>O<sub>4</sub> biosynthesized through the green synthesis of Silybum marianum and HA in the targeted delivery of 5-Fluorouracil to HCT116 cell line.","authors":"Atefeh Mansuryar, Shima Bourang, Mehran Noruzpour, Hossein Ali Ebrahimi, Amin Amani, Sergio Granados-Principal, Jesús Calahorra","doi":"10.1007/s40199-025-00568-9","DOIUrl":"10.1007/s40199-025-00568-9","url":null,"abstract":"<p><strong>Background and objectives: </strong>The administration of 5-FU as the first chemotherapeutic agent for colorectal cancer, showed difficulties including short half-life and the development of resistance. One prominent approach to overcome these restrictions, is administration of 5-FU in conjunction with nanoparticles, particularly magnetic nanoparticles. In this study, Fe<sub>3</sub>O<sub>4</sub> nanoparticles were prepared by the green synthesis and coated with polylactic acid-hyaluronic acid (PLA-HA) copolymer. Then, the HCT116 colorectal cancer cell line was used to assess the cytotoxicity and effectiveness of PLA/Fe<sub>3</sub>O<sub>4</sub> and PLA-HA/Fe<sub>3</sub>O<sub>4</sub> nanoparticles for the delivery of 5-FU medication.</p><p><strong>Methods: </strong>The characteristics of these copolymers were investigated by <sup>1</sup>H-NMR, FTIR and Thermogravimetric analysis. The nanoparticles were prepared using solvent diffusion technique and then characterized with different techniques like dynamic light scattering (DLS), TEM images, FTIR, UV-Vis spectroscopy, and VSM (Vibrational Sample Magnetometer). Ultimately, an assessment of drug encapsulation efficacy, the release profile and an in vitro analysis of cytotoxicity were performed to investigate the efficacy of drug delivery to HCT116 cells.</p><p><strong>Results: </strong>The results of NMR, FTIR and TGA analysis confirmed the successful synthesis of copolymers. A zeta potential of -18 mV and a spherical shape with an average size of 235 nm were characteristics of the synthesized PLA-HA/Fe<sub>3</sub>O<sub>4</sub>/5-FU nanoparticles. The encapsulation of Fe<sub>3</sub>O<sub>4</sub> nanoparticles in PLA-HA copolymer decreased their magnetic saturation, and VSM analysis showed that the nanoparticles possessed superparamagnetic properties. Additionally, the 5-FU encapsulation efficiency was 42%, and it demonstrated a burst and sustained release pattern. It was discovered that the acidic pH was more effective. The MTT assay proved the low toxicity and biocompatibility of drug-free nanocarriers'. Remarkably, compared to PLA/Fe<sub>3</sub>O<sub>4</sub>/5-FU micelles, the viability of HCT116 cells was found to be significantly reduced by PLA-HA/Fe<sub>3</sub>O<sub>4</sub>/5-FU micelles. This phenomenon can be explained by the unique way that hyaluronic acid interacts with overex CD44 receptors.</p><p><strong>Conclusion: </strong>One potential strategy for targeted drug delivery and HCT116 cell line control is to encapsulate 5-FU in magnetite nanoparticles (Fe<sub>3</sub>O<sub>4</sub>) made by the green synthesis method and use HA as cell-surface receptors to create PLA-HA/Fe<sub>3</sub>O<sub>4</sub>/5-FU nanoparticles. Nanocarriers favorable physicochemical characteristics and potent apoptotic effects make them promising agents for precisely delivering drugs to colon cancer cells.</p><p><strong>Highlights: </strong>• Drug delivery efficiency is significantly improved while utilizing ","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"33 2","pages":"27"},"PeriodicalIF":2.1,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12314301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pre-emptive hydrocortisone therapy in early septic shock: a double-blind, allocation-concealed, pilot randomized controlled trial.","authors":"Ehsan Emami, Emad Molaei, Samrand Fattah Ghazi, Marjan Sohrabi, Hossein Khalili","doi":"10.1007/s40199-025-00571-0","DOIUrl":"10.1007/s40199-025-00571-0","url":null,"abstract":"<p><strong>Background: </strong>Sepsis, a major global health issue, often progresses to septic shock with high morbidity and mortality. Corticosteroids especially low-dose hydrocortisone have shown promise in septic shock management. However, the role of hydrocortisone as pre-emptive therapy in early septic shock remains unclear.</p><p><strong>Objective: </strong>This study investigates the effects of pre-emptive administration of low-dose, short-course hydrocortisone on outcomes in patients with early septic shock.</p><p><strong>Methods: </strong>A double-blind, randomized controlled trial was conducted, enrolling individuals with early septic shock. Patients were randomized to receive either low-dose, short-course hydrocortisone (50 mg every 6 h for 48 h) as pre-emptive therapy or usual care. The primary outcome was vasopressor requirement.</p><p><strong>Results: </strong>Pre-emptive low-dose, short-course hydrocortisone significantly reduced the duration of vasopressor therapy (P = 0.03), cumulative vasopressor dose (38.52 mg vs. 99.11 mg, P = 0.02), and the necessity for mechanical ventilation (10% vs. 40%, P = 0.02). The hydrocortisone group exhibited a lower incidence of septic shock (20% vs. 40%), although this difference was not statistically significant (P = 0.17). No significant differences were observed in mortality rates (2 deaths per group), Sequential Organ Failure Assessment (SOFA) scores (P = 0.29), or ICU length of stay (P = 0.66). Serious adverse events were comparable between the two groups.</p><p><strong>Conclusions: </strong>Although pre-emptive hydrocortisone did not change the progression from early septic shock to septic shock, it significantly reduced both the duration of vasopressor therapy and the cumulative vasopressor dose in patients who entered the shock phase, without any significant adverse events.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"33 2","pages":"25"},"PeriodicalIF":2.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12287476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}