Pharmaceuticals最新文献

{"title":"Development and Evaluation of Liposomal <i>Celastrol</i>-PROTACs for Treating Triple-Negative Breast Cancer.","authors":"Xuebin Li, Chaoqun Yu, Gongyi Zheng, Yanghong Li, Weiguo Cao, Fan Wang","doi":"10.3390/ph18091381","DOIUrl":"10.3390/ph18091381","url":null,"abstract":"<p><p><b>Background:</b> Based on our previous study, <i>Celastrol</i>-based proteolysis-targeting chimeras (<i>Celastrol</i>-PROTACs) were shown to induce apoptosis in 4T1 cells by selectively degrading GRP94 and CDK1/4 through the endogenous ubiquitin-proteasome system. However, their clinical translation is limited by poor solubility, low targeting efficiency, and liver and kidney toxicity. <b>Methods:</b> To address these limitations, we developed a pegylated liposomal formulation of <i>Celastrol</i>-PROTACs (Lip-<i>Celastrol</i>-PROTACs) and evaluated its therapeutic efficacy and safety profile. <b>Results:</b> The tumor volume of the mice in the <i>Celastrol</i>-PROTACs solution group (286 ± 79 mm³) was significantly larger than that of those in the Lip-<i>Celastrol</i>-PROTACs group (229 ± 49 mm³) on day 18 after intravenous administration (<i>p</i> < 0.01). This difference between the two groups was statistically significant (<i>p</i> < 0.01). Notably, the <i>Celastrol</i>-PROTACs group exhibited significantly greater weight loss compared to the Lip-<i>Celastrol</i>-PROTACs group (<i>p</i> < 0.001). In vivo toxicity assessments revealed that the levels of AST and BUN in the <i>Celastrol</i>-PROTACs group were 27.93 ± 4.88 U/L and 12.36 ± 1.33 μmol/L, respectively, whereas those in the Lip-<i>Celastrol</i>-PROTACs group were found to be 7.92 ± 0.94 U/L and 8.19 ± 0.67 μmol/L, respectively. These findings indicate a statistically significant difference between the two formulations (<i>p</i> < 0.01). <b>Conclusions:</b> Our research demonstrated that pegylated liposomes could improve the targeting efficiency and minimize the toxicity of PROTACs, thereby improving overall therapeutic efficacy. These findings indicated that Lip-<i>Celastrol</i>-PROTACs represent a promising strategy for future clinical applications.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177739","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":"Self-Assembly 4-Butylresorcinol Deep Eutectic Solvent Nanoparticles for Efficient Transdermal Delivery and Whitening.","authors":"Hongtao Han, Dan Hu, Yaoming Deng, Jiayi Song, Yuyang Sheng, Jingxin Liu, Chengyu Wu, Bin Zeng","doi":"10.3390/ph18091383","DOIUrl":"10.3390/ph18091383","url":null,"abstract":"<p><p><b>Background:</b> Skin whitening agents often face challenges such as poor stability and low permeability. To overcome these issues, a novel 4-butylresorcinol (4-BR)/D-a- Tocopherol Polyethylene Glycol Succinate (TPGS) deep eutectic solvent (DES) system was developed, which can self-assemble into carrier-free nanoparticles (NPs). <b>Methods</b>: The 4-BR/TPGS DES was synthesized and characterized by theoretical calculations, DSC, FTIR, 1H-NMR, and 2D NMR to confirm its successful formation. <b>Results</b>: The self-assembled 4-BR/TPGS DES NPs showed a 3.46-fold increase in skin permeability, a 1.53-fold improvement in 4-BR stability, a 1.55-fold increase in melanin inhibition in B16 cells, and a 2.16-fold higher melanin suppression in zebrafish compared with traditional 4-BR oil-based formulations. These results indicated the excellent whitening efficacy and transdermal delivery potential of this formulation. <b>Conclusions</b>: The combination of TPGS-based DES and self-assembly technology represents a revolutionary approach for advanced transdermal delivery and the development of skin care products.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177649","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":"Preclinical Evaluation of Nanoemulsion and Polymeric Nanocapsule Delivery Systems of 4-(Phenylselanyl)-2H-Chromen-2-One for Rheumatoid Arthritis and Comorbidities.","authors":"Caren Aline Ramson da Fonseca, Vinicius Costa Prado, Letícia Cruz, Vanessa Macedo Esteves da Rocha, Ana Paula Bonato Wille, Angélica Schiavom Dos Reis, Jean Carlo Kazmierczak, Ricardo Frederico Schumacher, Ethel Antunes Wilhelm","doi":"10.3390/ph18091379","DOIUrl":"10.3390/ph18091379","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Recognizing the current limitations in rheumatoid arthritis (RA) treatments, especially in managing pain and inflammation, there is an urgent need to develop and explore new therapeutic strategies. In this study, we devised two innovative approaches using nanotechnology for treating RA. We evaluated the effectiveness of compound 4-(phenylselanyl)-2H-chromen-2-one (4-PSCO) in three forms: free, as well as in nanoemulsified (4-PSCO NE) and nanoencapsulated (4-PSCO NC) formulations. <b>Methods:</b> Arthritis was induced in mice by intraplantar injection of Freund's complete adjuvant (CFA; 0.1 mL). The 4-PSCO free, 4-PSCO NE, and 4-PSCO NC (1 mg/kg, orally) treatments were administered daily for 15 days. We assessed disease signs, symptoms, mechanical and thermal sensitivities, neurobehavioral deficits, and activities of myeloperoxidase (MPO), Na⁺, K⁺-ATPase, and acetylcholinesterase (AChE), as well as oxidative stress markers. <b>Results:</b> Our study demonstrates, for the first time, that both 4-PSCO NC and 4-PSCO NE inhibit the clinical signs of RA in mice, including inflammation. Moreover, both formulations alleviated pain and anxiety behaviors while restoring AChE activity and decreasing oxidative stress in the cerebral cortex. Notably, only the 4-PSCO NC treatment increased the time animals spent in the open arms of the elevated plus-maze. It lowered TBARS levels in the cerebral cortex, spinal cord, and paws, showcasing its advantages over the free 4-PSCO and 4-PSCO NE. <b>Conclusions:</b> These findings highlight the therapeutic potential of 4-PSCO, especially the polymeric nanocapsule, as a practical option for treating both the symptoms and underlying mechanisms of RA.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177362","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":"miR-25-3p Modulates Tumor Aggressiveness and Ferroptosis Escape in T24 Bladder Cancer Cells In Vitro.","authors":"Andresa Hiromi Sakai, Érica Romão Pereira, Anna Gabriele Prado Dos Santos, Débora Hipólito Quadreli, Luan Vitor Alves de Lima, Diego Luis Ribeiro, Samira Rahimirad, Carolina Mathias, Monyse de Nóbrega, Mário Sérgio Mantovani, Glaura Scantamburlo Alves Fernandes, Ilce Mara de Syllos Cólus, Juliana Mara Serpeloni","doi":"10.3390/ph18091382","DOIUrl":"10.3390/ph18091382","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Urothelial bladder carcinoma (UBC) is one of the most prevalent malignancies worldwide, and efforts have intensified to identify molecular markers that improve the prognosis and reduce treatment costs. Among the regulators of tumor behavior, microRNAs (miRNAs) have emerged as promising biomarkers for cancer diagnoses and treatment. The modulation of miR-25-3p has been associated with pancreatic, colorectal, and lung cancers; its role in UBC remains poorly explored. In this study, we investigated the effects of miR-25-3p modulation in a high-grade and muscle-invasive bladder cancer (MIBC) cell line (T24), using in vitro functional assays and bioinformatics approaches. <b>Results:</b> Bioinformatics analyses using TCGA-BLCA datasets revealed that miR-25-3p is upregulated in tumor tissues compared to non-tumor tissues, prompting an investigation into its molecular targets and related pathways. The transfection of T24 cells with an miR-25-3p mimic and inhibitor led to respective overexpression (11.16-fold) and downregulation (-2.82-fold) compared to the negative control. Functionally, miR-25-3p overexpression increased cell proliferation, viability, and migration, while its inhibition decreased the cell migration capacity. A gene expression analysis revealed that miR-25-3p overexpression resulted in the downregulation of <i>TP53</i>, <i>AIFM1</i>, <i>NFE2L2</i>, <i>TFRC</i>, <i>ACSL4</i>, <i>SLC7A11</i>, and <i>SLC3A2</i>, whereas <i>MMP9</i>, <i>MMP11</i>, and <i>GPX4</i> were upregulated, suggesting a role in both migration and ferroptosis regulation. In the inhibitor group, increased <i>SLC3A2</i> and decreased <i>MMP11</i> expression further supported this connection. Our results using an in vitro model for MIBC with the transfection of T24 cells suggest that miR-25-3p influences key pathways involved in oxidative stress and cell death, promoting a more aggressive tumor phenotype. <b>Conclusions:</b> The modulation of miR-25-3p impacts the behavior of T24 bladder cancer cells and may indicate its role in disease progression. Our results underscore the potential of miR-25-3p as a prognostic biomarker and support further studies considering its therapeutic relevance in managing high-grade and muscle-invasive bladder cancer.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177646","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":"Hybrid and Chimeric Heterocycles for the Inhibition of Carbonic Anhydrases.","authors":"Niccolò Paoletti, Simone Giovannuzzi, Claudiu T Supuran","doi":"10.3390/ph18091387","DOIUrl":"10.3390/ph18091387","url":null,"abstract":"<p><p>The design of multitarget drugs is a growing strategy to address complex and multifactorial diseases, and heterocycles play a major role in this approach. This review aims to critically analyze the role of heterocyclic scaffolds in the development of human carbonic anhydrase inhibitors (hCAIs), emphasizing their versatility as core chemotypes, linkers, and secondary pharmacophores. By examining advances from the last 10 years, we highlight how heterocycle-based designs contribute to modulating potency and selectivity toward hCAs, as well as to the creation of hybrid molecules with enhanced therapeutic profiles. Understanding these strategies is essential for guiding future drug discovery efforts targeting hCAs and related pathologies.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177676","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":"Click-to-Release for Controlled Immune Cell Activation: Tumor-Targeted Unmasking of an IL12 Prodrug.","authors":"Martijn H den Brok, Kim E de Roode, Luc H M Zijlmans, Laurens H J Kleijn, Marleen H M E van Stevendaal, Ron M Versteegen, Lieke W M Wouters, Raffaella Rossin, Marc S Robillard","doi":"10.3390/ph18091380","DOIUrl":"10.3390/ph18091380","url":null,"abstract":"<p><p><b>Objectives:</b> Immunotherapy utilizing immune-stimulating cytokines such as IL12 holds great promise for the treatment of cancer. However, clinical use of IL12 is hampered due to severe toxicity following systemic administration. We here present a novel treatment strategy in which IL12 is chemically silenced by conjugation to PEG masks that sterically hinder the receptor binding. Subsequently, the masks can be released on demand using a bioorthogonal click reaction, cleaving the linker connecting the masks, thereby restoring the native cytokine. This \"click-to-release\" approach is based on the highly selective Inverse electron-demand Diels-Alder (IEDDA) pyridazine elimination reaction between a tetrazine (Tz) and a <i>trans</i>-cyclooctene (TCO), optimized for fast reaction kinetics and in vivo compatibility. Selective activation in the tumor microenvironment is achieved by pretargeting one component of this reaction to the tumor, triggering local activation of the masked IL12 once it is given in a secondary i.v. injection. <b>Methods:</b> IL12 masking and unmasking were evaluated in vitro with PAGE and HEK-Blue reporter cells and ex vivo with ELISA. Biodistribution in mice was evaluated with I-125 radiolabeling and biotin-click histochemistry. <b>Results:</b> Several designs were evaluated and optimized in vitro, resulting in an IL12-TCO-PEG construct that exhibited superior masking and subsequent reactivation upon reaction with a tetrazine bound to a TAG-72-targeted diabody. In tumor-bearing mice, we demonstrated that this diabody-tetrazine could efficiently pre-localize tetrazine in the tumor. Administration of IL12-TCO-PEG 24 h later afforded efficient and selective unmasking in tumors, but not in the blood. <b>Conclusions:</b> These results demonstrate proof of principle of the click-cleavable IL12 prodrug approach and showcase the versatility of the click-to-release reaction.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177529","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":"Nanotechnology for the Efficacious Delivery of Medicinal Cannabis and Pharmaceutical Medicines.","authors":"Luis Vitetta, Jeremy David Henson, Evan Hayes, David Rutolo, Sean Hall","doi":"10.3390/ph18091385","DOIUrl":"10.3390/ph18091385","url":null,"abstract":"<p><p>The application of nanoparticles as nanomedicines, particularly for the targeted and efficacious delivery of drugs is an expanding platform in the field of cannabinoid and pharmaceutical drug delivery. By refocusing the route of drug administration beyond the oral gut pathway, this technology provides significant advancements that are especially relevant for cancer treatments. Orally administered drugs face significant challenges as they traverse the gastrointestinal tract (GIT) and are subject to first-pass GIT metabolism. Physiological conditions encountered in the GIT such as food effects, hormones, gastric pH, emptying time, and intestinal transit time vary widely across individuals. Fluid composition and enzymatic activity in the small intestine and large bowel also influence drug dissolution and absorption. These factors in conjunction with the intestinal cohort of bacteria can metabolize drugs before absorption, contributing to poor and variable drug bioavailability, which can be exacerbated by gut dysbiosis. Drug delivery that bypasses the oral-GIT route and hence first-pass metabolism offers a plausible solution for enhanced safety and drug efficacy.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177749","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":"Metagenomic Characterization of Gut Microbiota in Children with Autism Spectrum Disorder: Microbial Signatures and Modulation by Anti-Inflammatory Diet and Probiotics.","authors":"Marysol Valencia-Buitrago, Rodrigo Dias Oliveira-Carvalho, Valbert Cardoso, Jessica Triviño-Valencia, Luisa Matilde Salamanca-Duque, Vanessa Martínez-Díaz, Jovanny Zabaleta, Narmer Fernando Galeano-Vanegas, Carlos Andrés Naranjo-Galvis","doi":"10.3390/ph18091376","DOIUrl":"10.3390/ph18091376","url":null,"abstract":"<p><p><b>Background:</b> Autism Spectrum Disorder (ASD) is increasingly associated with alterations in gut microbiota, intestinal permeability, and immune dysregulation. However, integrative studies exploring these mechanisms in Latin American populations are lacking. <b>Objective:</b> To characterize gut microbiota profiles in Colombian children with ASD and evaluate the effects of two microbiota-targeted interventions, an anti-inflammatory diet and a probiotic formulation, on microbial diversity and taxonomic composition. <b>Methods:</b> In a two-phase study, shotgun metagenomic sequencing was performed on fecal samples from 23 children with ASD and 7 typically developing (TD) controls. In the second phase, 17 children with ASD were randomized to receive a 12-week intervention (anti-inflammatory diet, probiotics, or no intervention). Alpha diversity indices (Shannon, Pielou, and Chao1) and differential abundance analyses were conducted. <b>Results:</b> Compared to TD children, those with ASD showed a higher <i>Firmicutes/Bacteroidetes</i> ratio and a significantly increased abundance of genera such as <i>Clostridioides</i>, <i>Thomasclavelia</i>, <i>Alistipes</i>, and <i>Coprococcus</i>. The presence of functional gastrointestinal disorders (FGIDs) in ASD patients is associated with reduced microbial richness. POST-intervention, the anti-inflammatory diet group showed that no statistically significant changes in alpha diversity were observed, although a slight upward trend was noted and significant enrichment of six bacterial genera, including <i>Moraxella</i> and <i>Eubacterium</i>. The probiotic group exhibited a significant increase in <i>Romboutsia</i> and a decrease in <i>Lachnospira</i>. Cytokine-microbiota networks in ASD were fragmented and dominated by IFN-γ and MCP-1 hubs, indicating systemic immune activation. Interventions induced functional remodeling: The anti-inflammatory diet increased the number of beneficial genera (<i>Eubacterium</i>, <i>Adlercreutzia</i>) and shifted networks toward positive correlations involving IL-8 and MIP-1β. Probiotics increased <i>Romboutsia</i>, reduced <i>Lachnospira</i>, and restructured networks with regulatory cytokines (SDF-1α, Eotaxin) and SCFA-producing taxa (<i>Blautia</i>, <i>Roseburia</i>). <b>Conclusions:</b> Children with ASD in Colombia displayed distinct microbial profiles characterized by pro-inflammatory taxa and altered richness. Both the anti-inflammatory diet and probiotics produced compositional shifts in the gut microbiota, although global changes in diversity were limited. These findings support the potential of microbiota-targeted nutritional strategies for ASD and underscore the need for precision interventions tailored to specific clinical and microbial phenotypes.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177585","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":"Small Molecule Protease Inhibitors as Model Peptidomimetics.","authors":"Patricia Gomez-Gutierrez, Juan J Perez","doi":"10.3390/ph18091377","DOIUrl":"10.3390/ph18091377","url":null,"abstract":"<p><p>Proteases constitute one of the largest sub-classes of enzymes, accounting for ca. 2% of the proteins encoded in the human genome. They play a key role in protein degradation and signaling, regulating a variety of physiological processes. Dysregulation of their activity is associated with various pathological conditions like cancer, neurodegenerative disorders, inflammatory or cardiovascular diseases. Protease activity can be controlled by regulating enzyme concentrations, but also by inhibitors, molecules that modulate enzyme function, inspiring the development of small molecule protease inhibitors for therapeutic purposes. Protease inhibitors can be designed from the corresponding substrates by isostere replacement at the scissile bond. This process yields a first-generation of inhibitors that usually exhibit poor drug-like profiles that need subsequently be improved to generate a second-generation, by smoothing their peptide-like features. This process is reviewed in the present report and exemplified in the successful discovery stories of different inhibitors that correspond to four types of proteases, including the angiotensin converting enzyme (metalloprotease); HIV protease (aspartate protease); thrombin (serine protease) and the proteasome (threonine protease). A detailed description of the stories behind their design from their initial discovery to the final product is described in this report. Moreover, despite successful discovery stories, the challenges associated with designing novel protease inhibitors are examined. Finally, the relevance of these drugs in the present drug market is also reported.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177691","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":"Design and Characterization of Thermosensitive Niosomes as Platforms for Daunorubicin Delivery.","authors":"Viliana Gugleva, Katerina Ahchiyska, Elena Drakalska-Sersemova, Rositsa Mihaylova, Natalia Toncheva-Moncheva, Erik Dimitrov, Krum Aleksandrov, Aleksander Forys, Barbara Trzebicka, Denitsa Momekova","doi":"10.3390/ph18091375","DOIUrl":"10.3390/ph18091375","url":null,"abstract":"<p><p><b>Background/Objectives:</b> The study describes the elaboration and evaluation of thermosensitive niosomes intended for the systemic application of daunorubicin hydrochloride. The attained stimulus sensitivity would determine the release of the chemotherapeutic predominantly at the target site, which ensures a higher drug concentration and leads to reduced systemic toxicity. The latter is highly beneficial, as the anthracycline antibiotic is known for its dose-dependent cardiotoxic effects. <b>Methods</b>: Conventional and copolymer-modified niosomes were prepared via thin-film hydration and the transmembrane ammonium gradient method, allowing us to assess the impacts of copolymer type-DHP-PiPOX (1,3-dihexadecyl-propane-2-ol-poly(2-isopropyl-2-oxazoline)) or DHP-PETEGA (1,3-dihexadecyl-propane-2-ol-poly(ethoxytriethylene glycol acrylate)) and their concentrations (0.5, 1, and 2.5 mol%), as well as the method of preparation, on the main physicochemical properties of the vesicles. Niosomes were characterized in terms of their size, polydispersity index (PDI), zeta potential, entrapment efficiency, morphology, and drug release properties. Thermosensitivity was evaluated by fluorescence studies, and the antiproliferative activity of optimized formulations was assessed against the acute myelocyte leukemia-derived HL-60 cell line. <b>Results</b>: Daunorubicin-loaded niosomes modified with DHP-PiPOX and DHP-PETEGA at 2.5 mol% exhibited suitable physicochemical properties for systemic application, with sizes below 200 nm (155 and 158 nm respectively), low PDI values of 0.25 and 0.29, spherical morphology, and high daunorubicin entrapment efficiency (68.6 and 66.5% respectively). The vesicles showed temperature-dependent drug release properties and superior antiproliferative activity compared to the free daunorubicin (IC₅₀ values of 6.91 and 8.54 vs. 12.14). <b>Conclusions</b>: The obtained results indicate that the developed thermosensitive nanovesicles may serve as a suitable drug delivery system for the systemic application of daunorubicin hydrochloride.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177730","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}