European Journal of Pharmaceutical Sciences最新文献

{"title":"Evaluation of folic acid-targeted gadolinium-loaded perfluorohexane nanodroplets on the megavoltage X-ray treatment efficiency of liver cancer.","authors":"Roghayeh Kamran Samani, Masoud A Mehrgardi, Fatemeh Maghsoudinia, Mohammad Najafi, Fatemeh Mehradnia","doi":"10.1016/j.ejps.2025.107059","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107059","url":null,"abstract":"<p><p>The efficacy of radiation therapy can decrease due to the inherent radioresistance of different tumor cells. Gadolinium shows significant potential as a radiosensitivity enhancer due to its high atomic number. In this study, a novel theranostic nanoprobe based on folic acid-conjugated gadolinium-loaded nanodroplets (FA-Gd-NDs) has been introduced for ultrasound imaging (USI)-guided radiation therapy of hepatocellular carcinoma. The ultrasound echogenicity evaluation of NDs, Gd release studies, biocompatibility test of Gd-NDs, colony assay, cellular uptake of NDs via fluorescence microscopy, and flow cytometry analysis were performed on Hepa1-6 cancer and L929 normal cell lines. Our results showed that synthesized NDs significantly enhanced ultrasound signal intensity in PBS solution and agarose gel phantom. MTT and clonogenic assays indicated that Gd-NDs substantially reduced the cell viability and also surviving fraction of Hepa1-6 cancer cells under US and X-ray exposure. Additionally, FA-Gd-NDs exhibited sensitization enhancement factor (SER) of 1.8 after concurrent exposure to US and X-ray. Fluorescence imaging demonstrated more internalization of FA-Gd-NDs into cancer cells in comparison with normal cells. According to flow cytometry results, the Gd-NDs and FA-Gd-NDs uptake by L929 cell line were 20% and 28%, respectively, while their uptake by Hepa1-6 cells was 60% and 94%, respectively. In conclusion, the synthesized novel theranostic nanoprobe shows great potential for enhancing the efficacy of radiation therapy and enabling ultrasound image-guided radiation therapy of cancers.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107059"},"PeriodicalIF":4.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiologically-based pharmacokinetic modeling to predict the exposure and to assess pharmacodynamics of daptomycin in infants within 1 year old","authors":"Lingling Ye ,&nbsp;Hong Zhou ,&nbsp;Guimu Guo,&nbsp;Ming Chen,&nbsp;Jinhua Zhang","doi":"10.1016/j.ejps.2025.107058","DOIUrl":"10.1016/j.ejps.2025.107058","url":null,"abstract":"<div><div>Daptomycin is widely used in pediatric patients for serious infections caused by Gram-positive bacteria, however, studies regarding its safety and efficacy in infants within 1 year old are very limited. A physiologically-based pharmacokinetic (PBPK) model of daptomycin was built for children aged 1–17 years old and extrapolated to infants within 1 year old to evaluate pharmacodynamics (PD) based on efficacy and safety considerations. Monte Carlo Simulations (MCSs) were conducted to determine the probabilities of target attainment (PTA) and cumulative fractions of response (CFR) of daptomycin. The pharmacokinetic (PK) of daptomycin did not differ much in the population of infants within 1 year of age, with peak plasma concentration (C_max) and area under the curve (AUC) maintained at an approximate level at all months of age, while the average trough concentration of daptomycin was 3.49 μg/mL when 10 mg/kg daptomycin was given, and 4.98 ug /mL at 15 mg/kg. According to the results of the MCSs, 10mg/kg daptomycin provides good antimicrobial effect for S.pneumoniae and MSSA. With the increase of dosage, the CFR value of daptomycin against MRSA, E.faecalis and E.faecium also gradually reached &gt;90 %, except for E.faecalis with an average CFR of only 82.94 % at 12mg/kg. This is a daptomycin PBPK model in infants within 1 year of age, dose regimen higher than 10 mg/kg should be recommended for this population in the treatment of MRSA, E. faecalis, and E. faecalis.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"208 ","pages":"Article 107058"},"PeriodicalIF":4.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562933","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":"Clinical Efficacy and Mechanistic Insights of FDA-Approved HDAC Inhibitors in the Treatment of Lymphoma.","authors":"Nasreddine El Omari, Saad Bakrim, Hamza Elhrech, Tarik Aanniz, Abdelaali Balahbib, Learn-Han Lee, Waleed Al Abdulmonem, Abdelhakim Bouyahya","doi":"10.1016/j.ejps.2025.107057","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107057","url":null,"abstract":"<p><p>Lymphomas are complex malignancies of blood cells, characterized by the malignant transformation of lymphocytes. This transformation is partially driven by disruptions in epigenetic regulation, particularly the acetylation of histones. Among the key players in this process are histone deacetylases (HDACs), whose aberrant activity contributes significantly to lymphoma development. Consequently, targeting HDACs represents a promising pharmacotherapeutic approach. Several HDAC inhibitors (HDACis) have demonstrated significant anticancer effects, with four FDA-approved molecules-vorinostat, romidepsin, belinostat, and panobinostat-forming critical components of chemotherapy regimens for lymphoma treatment. These HDAC inhibitors exhibit their therapeutic efficacy through mechanisms that indirectly impact cellular memory and induce cancer cell death via apoptosis and cell cycle arrest. Their clinical effectiveness is particularly notable in various types of lymphomas, underscoring their therapeutic potential. The objective of this review is to provide a detailed analysis of FDA-approved HDACis, focusing on their molecular mechanisms of action and clinical applications in lymphoma treatment. Specifically, we aim to elucidate how these inhibitors modulate epigenetic regulation to achieve therapeutic efficacy, highlight their utility across different lymphoma subtypes, and examine their integration into combination therapies with other anticancer agents. Furthermore, this review seeks to identify gaps in current knowledge and propose directions for future research, including the development of next-generation HDAC inhibitors and strategies for optimizing their clinical use. By consolidating existing evidence, we strive to enhance the understanding of HDACis' role in lymphoma therapy and inspire advancements in their therapeutic potential.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107057"},"PeriodicalIF":4.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual centrifugation as fast and novel screening approach for optimal RNA loaded lipid-based nanoparticles.","authors":"Valentin Bender, Christian Smolka, Franziska Pankratz, Monika Köll-Weber, Ulrich Massing, Regine Süss","doi":"10.1016/j.ejps.2025.107056","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107056","url":null,"abstract":"<p><p>The last decade has shown increased benefits for non-viral gene delivery. To overcome the challenges of nucleic acid administration, appropriate drug delivery systems (DDS) are required. The recently approved RNA formulations have demonstrated that lipid nanoparticles (LNPs) are suitable DDS for delivering RNAs. LNPs are commonly composed of cationic and/or ionizable lipids, helper lipids and PEGylated lipids. Conventional manufacturing procedures for LNPs are mixing systems, such as microfluidics, with drawbacks in terms of time and resource consumption. The LNPs produced also pose problems with storage stability. Based on a microRNA (miRNA) model, we present dual centrifugation (DC) as a novel and reproducible way for RNA loaded LNP formulation via in-vial homogenization. Our formulations show promising results in size characteristics, as well as in their cell performance. Depending on the lipid composition of the LNPs, a remarkable knockdown efficiency is achieved. With a net formulation time of 7 minutes, an enormously fast approach can be presented. DC offers the capability for fast LNP screenings, with a loading capacity of up to 40 vials per run. The simplicity of the method allows us to take advantage of bedside preparation, overcoming the hurdles of storage stability for LNP formulations.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107056"},"PeriodicalIF":4.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Novel Role and Mechanistic Insights of Skeletal Muscle Relaxant Cyclobenzaprine Hydrochloride in Esophageal Squamous Cell Carcinoma Treatment.","authors":"Xiao Liu, Jibing Cheng, Maoju Tang, Chongbo Liao, Yong Yang, Man Luo, Lei Xu, Xiaowu Zhong, Qiang Ma, Xiaolan Guo","doi":"10.1016/j.ejps.2025.107051","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107051","url":null,"abstract":"<p><strong>Objective: </strong>Cyclobenzaprine hydrochloride (Flexeril) is a muscle relaxant primarily used to relieve muscle pain and spasms. However, its potential anti-cancer role remains largely unexplored. This study aims to investigate the inhibitory effect of Flexeril on esophageal squamous cell carcinoma (ESCC) and to uncover the molecular mechanisms through which it affects the proliferation and metastasis of ESCC.</p><p><strong>Methods: </strong>A compound library approved by the FDA was employed to screen drugs with inhibitory effects on ESCC. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay, and Plate colony formation was analyzed to evaluate the proliferative ability of ESCC cell lines (KYSE150 and Eca109) after treatment with Flexeril. Migratory ability was examined through Transwell and Scratch assays. Proteomics was performed to identify proteins regulated by Flexeril in KYSE150 and Eca109 cells. RT-PCR and Western blot were used to detect changes in related genes at the mRNA and protein levels after treatment with Flexeril. Drug affinity responsive target stability (DARTS) assay and cellular thermal shift assay (CETSA) were employed to identify the binding of Flexeril and JAK1 protein. Additionally, the comet assay was conducted to assess the DNA damage response in ESCC cells following WDHD1 knockdown or Flexeril exposure. Finally, tumor‑bearing nude mice model were constructed to evaluate the in vivo anticancer effects of Flexeril on ESCC.</p><p><strong>Results: </strong>Flexeril significantly inhibited the proliferation and migration of ESCC cells in a time- and dose-dependent manner. Proteomics analysis identified WDHD1 as a downstream target of Flexeril exposure, and knockdown of WDHD1 mimicked the effects of Flexeril on proliferation and migration of ESCC. Conversely, overexpression of WDHD1 attenuated the inhibitory effects of Flexeril on ESCC. Mechanistically, the JAK1-STAT3 signaling pathway, but not the JAK2-STAT3 or PI3K-Akt-mTOR pathways, was involved in regulating WDHD1 expression in ESCC cells following Flexeril treatment. Overexpression of STAT3 or WDHD1 mitigated the inhibitory effects of Flexeril on ESCC proliferation and migration. Moreover, both Flexeril exposure and WDHD1 knockdown induced a DNA damage response (DDR) in ESCC cells. In addition, Flexeril significantly inhibited the growth of ESCC tumors in nude mice, downregulating the JAK1-STAT3-WDHD1 signaling pathway, with no significant damage observed in vital organs such as the heart, liver, spleen, lungs, or kidneys, as shown by histological examination.</p><p><strong>Conclusion: </strong>Flexeril exhibits anti-cancer effects in ESCC by inhibiting the JAK1-STAT3-WDHD1 axis and inducing DDR. These findings suggest that Flexeril may serve as a potential novel therapeutic agent for the treatment of ESCC.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107051"},"PeriodicalIF":4.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NGF regulates survival and differentiation of umbilical mesenchymal stem/stromal cells into GABAergic, dopaminergic and cholinergic lineages","authors":"Paulina Borkowska ,&nbsp;Małgorzata Kowalczyk ,&nbsp;Aleksandra Zielińska ,&nbsp;Karol Poskrobko ,&nbsp;Magdalena B Rother ,&nbsp;Monika Paul-Samojedny ,&nbsp;Jan Kowalski","doi":"10.1016/j.ejps.2025.107053","DOIUrl":"10.1016/j.ejps.2025.107053","url":null,"abstract":"<div><div>Mesenchymal stem cells advantageous properties have led scientists to conduct trials on a range of medical conditions, including incurable neurodegenerative diseases. Wharton-Jelly derived mesenchymal stem cells, given their ease of collection, are frequently selected for these studies. This research aimed to investigate the effects of nerve growth factor (<em>NGF</em>) gene overexpression on the neural differentiation, survivability, and gene and protein expression of these cells. The level of gene expression was tested using the ddPCR method.</div><div>Six umbilical cords from donors were collected, and three randomly chosen primary cultures of Wharton-Jelly derived mesenchymal stem cells were used in experiment. Cells were transduced with lentiviral vectors and underwent a 12-day differentiation process.</div><div>The results revealed neuron-like cells with significantly high expression of <em>CHAT, GAD2</em> and <em>TH</em> genes. A corresponding increase in protein expression was also observed. Immunostaining demonstrated notable differences in neuron-like phenotypes, contingent on the environmental conditions of the research groups. Throughout the experiment, samples with transduced mesenchymal stem cells overexpressing the <em>NGF</em> gene showed the highest expression levels from almost all of studied genes and proteins, and were also the most phenotypically similar to neuron-like cells.</div><div>The study concluded that sustained overexpression of <em>NGF</em>:</div><div>guides mesenchymal stem cells towards the neural pathway,</div><div>facilitates the differentiation of modified mesenchymal stem cells into GABAergic, dopaminergic, and cholinergic neuron-like cells,</div><div>suggests that GABAergic neurons’ marker predominantly co-expresses with other neurons’ markers, such as cholinergic or dopaminergic ones,</div><div>increases survivability of modified mesenchymal stem cells in toxic conditions;</div><div>The limitations of the study is that we merely know that cells have begun to express neurogenic markers, but in the absence of standards for mature neuronal markers, we do not yet know how far they have progressed as differentiating cells.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"208 ","pages":"Article 107053"},"PeriodicalIF":4.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515102","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":"Prediction of surfactant-mediated dissolution of poorly soluble drugs from drug powder","authors":"Roshni P. Patel,&nbsp;Erik B. Nordquist,&nbsp;James E. Polli","doi":"10.1016/j.ejps.2025.107052","DOIUrl":"10.1016/j.ejps.2025.107052","url":null,"abstract":"<div><div>Beyond rough “what if” estimation, in vitro dissolution is infrequently predicted. The objective was to assess the predictability of a powder dissolution model with a single diffusion layer thickness model, where dissolution of various drugs was facilitated by several surfactant micelles. Powder dissolution of three poorly water soluble drugs (i.e., posaconazole, ritonavir, and griseofulvin) was measured into buffer, as well as four surfactant solutions [i.e., sodium lauryl sulfate (SLS), polysorbate 80 (PS80), polyoxyethylene (10) lauryl ether (POE10), and cetyltrimethylammonium bromide (CTAB)]. Drug solubility, micelle sizing, and powder sizing were also performed. Prediction of drug dissolution employed the film dissolution model, applied to spherical drug particle fractions of the percent weight particle size distribution, and with a surfactant-mediated dissolution component. There were two competing models for diffusion layer thickness: fixed thickness (i.e., h_fixed) and radius-dependent thickness (i.e., h_max) models. SLS, PS80, POE10, and CTAB increased the dissolution of posaconazole, ritonavir, and griseofulvin, compared to no-surfactant buffer. Results show that in vitro drug dissolution from various polydisperse powders into several surfactant solutions was successfully predicted using a surfactant-mediated dissolution model. The best diffusion layer thickness for the fixed thickness model and the radius-dependent model were separately found to be h_fixed = 12 µm and h_max = 12 µm, respectively, with h_fixed = 12 µm being the more preferred. Also, the powder dissolution model where powder was parameterized in terms of its entire particle size distribution was successful in predicting observed dissolution profiles using each h_fixed = 12 µm and h_max = 12 µm; model use of a mean particle size was also successful in prediction using h_fixed = 12 µm. Credibility assessment of the in vitro dissolution model was performed, including model verification and validation considerations in light of the question of interest, the context of use, and model risk.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"208 ","pages":"Article 107052"},"PeriodicalIF":4.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511901","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":"GDNF reduces fibril-induced early-stage alpha-synuclein pathology after delivery of 20S proteasome inhibitor lactacystin","authors":"Safak Er ,&nbsp;Ilmari Parkkinen ,&nbsp;Karolina Trepczyk ,&nbsp;Anna Seelbach ,&nbsp;Maria Samuela Pasculli ,&nbsp;Francesca De Lorenzo ,&nbsp;Kelvin Luk ,&nbsp;Elzbieta Jankowska ,&nbsp;Piotr Chmielarz ,&nbsp;Andrii Domanskyi ,&nbsp;Mikko Airavaara","doi":"10.1016/j.ejps.2025.107048","DOIUrl":"10.1016/j.ejps.2025.107048","url":null,"abstract":"<div><div>Failures in protein homeostasis are linked to Parkinson's disease (PD) and other neurodegenerative diseases. Lewy bodies, proteinaceous inclusions rich in phosphorylated alpha-synuclein are a hallmark of PD. Glial cell line-derived neurotrophic factor (GDNF) can eliminate Lewy body-like inclusions in mouse dopamine neurons. This study explores whether GDNF has protective effects against alpha-synuclein protofibril toxicity under proteasome inhibition by lactacystin, both <em>in vitro</em> and <em>in vivo.</em> GDNF did not shield midbrain dopamine neurons from lactacystin-induced neurodegeneration, but still prevented phosphorylated alpha-synuclein accumulation. <em>In vivo</em> experiment with control or GDNF-expressing viral vectors assessed alpha-synuclein pathology spread in the nigrostriatal pathway and lactacystin-caused damage in the midbrain. GDNF overexpression reduced phosphorylated alpha-synuclein inclusions. Lactacystin-treated mice showed motor asymmetry and decreased spontaneous activity, exacerbated without AAV-GDNF pre-treatment. However, GDNF's neuroprotective effect could not be confirmed <em>in vivo</em>, due to side-effects from overexpression in the midbrain. Importantly, these findings show that GDNF continues to eliminate alpha-synuclein aggregation despite lactacystin-induced proteasome inhibition. Activating neurotrophic signaling pathways may protect against alpha-synuclein pathology in PD, even with impaired protein degradation mechanisms.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"208 ","pages":"Article 107048"},"PeriodicalIF":4.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482543","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":"Local delivery of lipid-based nanoparticles containing microbial nucleic acid for osteoimmunomodulation","authors":"N.R. Rahmani ,&nbsp;F. Jahanmard ,&nbsp;A. Hassani Najafabadi ,&nbsp;J. Flapper ,&nbsp;O. Dogan ,&nbsp;A. Khodaei ,&nbsp;G. Storm ,&nbsp;M. Croes ,&nbsp;M.C. Kruyt ,&nbsp;D. Gawlitta ,&nbsp;H. Weinans ,&nbsp;E. Mastrobattista ,&nbsp;S. Amin Yavari","doi":"10.1016/j.ejps.2025.107050","DOIUrl":"10.1016/j.ejps.2025.107050","url":null,"abstract":"<div><div>Osteoimmunomodulation is a strategy to promote bone regeneration in implants by modifying the immune environment. CpG-containing oligonucleotides type C (CpG ODN C) and Polyinosinic:polycytidylic acid (Poly[I:C]) are analogs of microbial nucleic acids that have been studied for various immunotherapeutic applications. This research investigates the potential of CpG ODN C and Poly(I:C) as an osteoimmunomodulatory agent for bone regenerative purposes. We encapsulated each nucleic acid in a lipid-based nanoparticle to facilitate the delivery into intracellular pathogen recognition receptors in immune cells. The lipid-based nanoparticles were ±250 nm in size with a negative charge (−36 to −40 mV) and an encapsulation efficiency of ±60 %. Lipid-based nanoparticles containing nucleic acids, Lip/CpG ODN C and Lip/Poly(I:C), increased the production of TNF, IL-6, and IL-10 by primary human macrophages compared to free-form nucleic acids. Conditioned medium from macrophages treated with CpG ODN C (10 µg/ml) and Lip/CpG ODN C (0.1, 1, and 10 µg/ml) promoted osteoblast differentiation of human mesenchymal stromal cells by 2.6-fold and 3-fold, respectively; no effect was seen for Lip/Poly(I:C). Bone implants were prepared, consisting of a biphasic calcium phosphate scaffold, bone morphogenetic protein (BMP) 2, and lipid-based nanoparticles suspended in gelatin methacryloyl (GelMA) hydrogel. Implants were evaluated for <em>de novo</em> bone formation in an extra-skeletal implantation model in rabbits for 5 weeks. Based on the particles suspended in GelMA, six groups of implants were prepared: Lip/CpG ODN C, Lip/Poly(I:C), Lip (empty), CpG ODN C, Poly(I:C), and a control group consisting of empty GelMA. After 5 weeks, healthy bone tissue formed in all of the implants with active osteoblast and osteoclast activity, however, the amount of new bone volume and scaffold degradation were similar for all implants. We suggest that the working concentrations of the nucleic acids employed were inadequate to induce a relevant inflammatory response. Additionally, the dosage of BMP-2 used may potentially mask the immune-stimulatory effect. Lip/CpG ODN C holds potential as a bioactive agent for osteoimmunomodulation, although further <em>in vivo</em> demonstration should corroborate the current <em>in vitro</em> findings.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"208 ","pages":"Article 107050"},"PeriodicalIF":4.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482544","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":"Enhancing the photothermal properties of indocyanine green in melanoma spheroids via encapsulation in Span 80-containing lipid nanocapsules","authors":"Siyang Wu ,&nbsp;Taher Hatahet ,&nbsp;Wafa' T. Al-Jamal","doi":"10.1016/j.ejps.2025.107049","DOIUrl":"10.1016/j.ejps.2025.107049","url":null,"abstract":"<div><div>Indocyanine green (ICG), a well-known photosensitiser, has shown potential in photothermal therapy (PTT) for cancer treatment, but its effectiveness is limited by poor skin penetration and rapid clearance. To address this, lipid nanocapsules (LNCs) were used as nanocarriers to enhance ICG's cellular uptake and photothermal (PT) performance in melanoma cells. Utilising our recently developed Span 80-modified LNCs (LNC100-S8) with high biocompatibility and enhanced cellular uptake in B16F10 melanoma cells, ICG was loaded into LNC100-S8 using the phase inversion temperature method. The results showed that ICG encapsulation at 4.5 mg/mL maintained small LNC sizes (95–105 nm). Moreover, the heating capacity of ICG in LNCs was approximately 1.5 times higher than free ICG, achieving temperature increases over 10 °C post-irradiation. In cell cancer monolayers, LNC100-S8 enhanced ICG uptake by 1.5 times compared to free ICG and reduced cell viability to 50 % following 808 nm laser irradiation. More promisingly, ICG-LNC100-S8 combined with laser irradiation significantly reduced three-dimensional B16F10 spheroids size up to 11 days post-treatment compared to free ICG. Overall, our findings validate LNC100-S8, as promising nanocarriers for enhancing ICG-based PTT, supporting their potential applications <em>in vivo</em> to treat melanoma and other skin cancers.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"208 ","pages":"Article 107049"},"PeriodicalIF":4.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482542","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}