Pharmaceutics最新文献

{"title":"Thymoquinone-Loaded Chitosan Nanoparticles Combat Testicular Aging and Oxidative Stress Through SIRT1/FOXO3a Activation: An In Vivo and In Vitro Study.","authors":"Enas A Kasem, Gehan Hamza, Nagi M El-Shafai, Nora F Ghanem, Shawky Mahmoud, Samy M Sayed, Mohammed Ali Alshehri, Laila A Al-Shuraym, Heba I Ghamry, Magdy E Mahfouz, Mustafa Shukry","doi":"10.3390/pharmaceutics17020210","DOIUrl":"https://doi.org/10.3390/pharmaceutics17020210","url":null,"abstract":"<p><p><b>Background:</b> Aging is a complex biological process characterized by the accumulation of molecular and cellular damage over time, often driven by oxidative stress. This oxidative stress is particularly detrimental to the testes, where it causes degeneration, reduced testosterone levels, and compromised fertility. D-galactose (D-gal) is commonly used to model aging as it induces oxidative stress, mimicking age-related cellular and molecular damage. Testicular aging is of significant concern due to its implications for reproductive health and hormonal balance. This research examines the protection by thymoquinone (TQ) or thymoquinone-loaded chitosan nanoparticles (NCPs) against D-galactose (D-gal)-induced aging in rat testes, focusing on biochemical, histological, and molecular changes. Aging, which is driven largely by oxidative stress, leads to significant testicular degeneration, reducing fertility. D-gal is widely used to model aging due to its ability to induce oxidative stress and mimic age-related damage. TQ, a bioactive ingredient of <i>Nigella sativa</i>, has earned a reputation for its anti-inflammatory, anti-apoptotic, and antioxidant characteristics, but its therapeutic application is limited by its poor bioavailability. <b>Methods</b>: Thymoquinone was loaded into chitosan nanoparticles (NCPs) to enhance its efficacy, and this was hypothesized to improve its stability and bioavailability. Four groups of male Wistar rats participated in the study: one for the control, one for D-gal, one for D-gal + TQ, and the last one for D-gal + NCP. <b>Results</b>: The results exhibited that D-gal substantially increased oxidative injury, reduced testosterone levels, and caused testicular damage. Treatment with TQ and NCPs significantly reduced oxidative stress, improved antioxidant enzyme levels, and restored testosterone levels, with NCPs showing a stronger protective effect than TQ alone. A histological analysis confirmed that NCPs better preserved testicular structure and function. Additionally, the NCP treatment upregulated the expression of key genes of oxidative stress resistance, mitochondrial function, and reproductive health, including SIRT1, FOXO3a, and TERT. <b>Conclusions:</b> The findings suggest that NCPs offer enhanced protection against aging-related testicular damage compared with TQ alone, which is likely due to the improved bioavailability and stability provided by the nanoparticle delivery system. This research emphasizes the potential of NCPs as a more effective therapeutic strategy for mitigating oxidative stress and age-related reproductive dysfunction. Future research should further explore the mechanisms underlying these protective effects.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502840","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 pH- and Temperature-Responsive Performance and Cytotoxicity of N-Isopropylacrylamide and Acrylic Acid Functionalized Bimodal Mesoporous Silicas with Core-Shell Structure and Fluorescent Feature for Hela Cell.","authors":"Huijie Ge, Xiaoli Wang, Shiyang Bai, Yuhua Bi, Fei Liu, Jihong Sun, Wenliang Fu, Donggang Xu","doi":"10.3390/pharmaceutics17020206","DOIUrl":"https://doi.org/10.3390/pharmaceutics17020206","url":null,"abstract":"<p><p><b>Background:</b> Polymer-coated mesoporous silica nanoparticles have attracted immense research interest in stimuli-responsive drug delivery systems due to their drug-releasing ability on demand at specific sites in response to external or internal signals. However, the relationships between the coated-copolymer encapsulation and drug delivery performance in the hybrid nanocomposites was rarely reported. Therefore, the main objectives of the present work are to explore the cell uptake, cellular internalization, cytotoxicity, and hemolysis performance of the fluorescent hybrid materials with different polymer-encapsulated amounts. <b>Methods:</b> Using (2-(2-aminoethyl)-6-(dimethylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione)-doped poly[(N-isopropylacrylamide)-co-(acrylic acid)] (PAN) as a shell and bimodal mesoporous silicas (BMMs) as a core, the dual pH- and temperature-responsive mesoporous PAN@M-BMMs with the fluorescent performances were synthesized via a radical polymerization approach. The effects of the PAN-coated thicknesses on their physicochemical properties and structural features were demonstrated via XRD and SAXS patterns, SEM and TEM images, FT-IR spectra, and TG analysis. Their mass fractal (<i>D_m</i>) evolutions were elucidated on the basis of the SAXS patterns and fluorescence spectra. <b>Results:</b> The <i>D_m</i> values increased from 2.74 to 2.87 with an increase of the PAN-coated amount from 17 to 26.5% along with the particle size from 76.1 to 85.6 nm and blue-shifting of their fluorescent emission wavelength from 470 to 444 nm. Meanwhile, the PAN@M-BMMs exhibited a high ibuprofen (IBU) loading capacity (13.8%) and strong dual pH-/temperature-responsive drug-releasing performances (83.1%) at pH 7.4 and 25 °C, as comparison with that (17.9%) at pH 2.0 and 37 °C. The simulated results confirmed that the adsorption energy decreased from -67.18 kJ/mol for pure BMMs to -116.76 kJ/mol for PAN@M-BMMs, indicating the PAN-grafting on the surfaces of the BMMs core was beneficial to improve its IBU-adsorption capacity. Its uptake in the HeLa cell line was performed via microplate readers, confocal microscopy, flow cytometry, and ICP measurement, showing a low cytotoxicity at a concentration up to 100 µg/mL. Specially, P_0.2AN@M-BMMs had a superior cellular uptake and fluorescence properties via the time-dependent uptake experiments, and exhibited the highest silicon content via the cellular internalization analysis, as compared to other carriers. Hemolysis tests confirmed the hemolysis rates below 5%. <b>Conclusions:</b> These demonstrations verified that PAN@M-BMMs should be a promising biomedical application prospect.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503246","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":"Preparing a Liposome-Aided Drug Delivery System: The Entrapment and Release Profiles of Doxorubicin and 9-(<i>N</i>-Piperazinyl)-5-methyl-12(<i>H</i>)-quino [3,4-b][1,4]benzothiazinium Chloride with Human Serum Albumin.","authors":"Danuta Pentak, Violetta Kozik, Andrzej Zieba, Marlena Paździor-Heiske, Aleksandra Szymczyk, Josef Jampilek, Andrzej Bak","doi":"10.3390/pharmaceutics17020202","DOIUrl":"https://doi.org/10.3390/pharmaceutics17020202","url":null,"abstract":"<p><p><b>Background/Objectives:</b> The principal aim of this work was to prepare a liposomal drug delivery system based on the commercial drug doxorubicin (DOX) and a budding agent with promising anticancer activity, 9-(<i>N</i>-piperazinyl)-5-methyl-12(<i>H</i>)-quino [3,4-b][1,4]benzothiazinium chloride (9-PBThACl). <b>Methods</b>: A spectrophotometric methodology was used to meticulously investigate the drug entrapment and release characteristics of the new liposomal complexes (L) based on dipalmitoylphosphatidylcholine (DPPC) with human serum albumin (HSA) and its defeated analog (dHSA). <b>Results</b>: The impact of the operational parameters (temperature and pH) on the liposome/drug(s)/(d)HSA, namely [L_{DPPC/9-PBThACl/DOX} ]:(d)HSA] systems, as well as the polarity of the phospholipid bilayer, was examined. In order to compare the experimental findings, mathematical models were employed to specify the analytical factors controlling the process of drug release/potential drug release from liposomes. The observed variations in the drug encapsulation and release profiles were due to the combination of liposomal conjugates with human plasma protein. <b>Conclusions</b>: It was proven that changes in the environmental pH directly affect the percentage of drug entrapment in liposomes and the medicine release efficiency. Moreover, the grouping tendency of the liposomal combinations was investigated using a principal component analysis (PCA) and a hierarchical clustering analysis (HCA). Finally, an analysis of variance (ANOVA) confirmed the statistical impact of pH buffering and changing temperature factors on the drug release characteristics of liposomal conjugates.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503224","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":"Non-Invasive Delivery of CRISPR/Cas9 Ribonucleoproteins (Cas9 RNPs) into Cells via Nanoparticles for Membrane Transport.","authors":"Toshihiko Tashima","doi":"10.3390/pharmaceutics17020201","DOIUrl":"https://doi.org/10.3390/pharmaceutics17020201","url":null,"abstract":"<p><p>The clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system is a promising biotechnology tool for genome editing. However, in living organisms, several pharmacokinetic challenges arise, including off-target side effects due to incorrect distribution, low bioavailability caused by membrane impermeability, and instability resulting from enzymatic degradation. Therefore, innovative delivery strategies must be developed to address these issues. Modified nanoparticles offer a potential solution for the non-invasive delivery of CRISPR/Cas9 ribonucleoproteins (Cas9 RNPs). Cas9 RNPs encapsulated in nanoparticles are protected from enzymatic degradation, similar to how microRNAs are shielded within exosomes. It is well-established that certain materials, including proteins, are expressed selectively in specific cell types. For example, the α-7 nicotinic receptor is expressed in endothelial and neuronal cells, while the αvβ3 integrin is expressed in cancer cells. These endogenous materials can facilitate receptor-mediated endocytosis or transcytosis. Nanoparticles encapsulating Cas9 RNPs and coated with ligands targeting such receptors may be internalized through receptor-mediated mechanisms. Once internalized, Cas9 RNPs could perform the desired gene editing in the nucleus after escaping the endosome through mechanisms such as the proton sponge effect or membrane fusion. In this review, I discuss the potential and advantages of delivering Cas9 RNP-encapsulated nanoparticles coated with ligands through receptor-mediated endocytosis or transcytosis.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503389","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":"Evaluation of Antibacterial Properties of Zinc Oxide Nanoparticles Against Bacteria Isolated from Animal Wounds.","authors":"Noppason Pangprasit, Aphisek Kongkaew, Duanghatai Saipinta, Surachai Pikulkaew, Montira Intanon, Witaya Suriyasathaporn, Wasana Chaisri","doi":"10.3390/pharmaceutics17020209","DOIUrl":"https://doi.org/10.3390/pharmaceutics17020209","url":null,"abstract":"<p><p><b>Background/Objectives:</b> This research aimed to determine the efficacy of metallic oxide nanoparticles, especially zinc oxide nanoparticles (ZnO-NPs), in inhibiting a wide range of bacteria isolated from animal wounds, indicating their potential as alternative antimicrobial therapies in veterinary medicine. <b>Method:</b> The disc diffusion technique, broth microdilution technique, and time-kill kinetic assay were performed to determine the antibacterial activity of the ZnO-NPs. <b>Results:</b> Transmission electron microscopy (TEM) and scanning electron microscopy (SEM showed that the ZnO-NPs were spherical and polygonal with sizes ranging from 50 to 100 nm, while DLS (NanoSizer) measured an average size of 512.3 to 535.7 nm with a polydispersity index (PDI) of 0.50 to 0.63 due to particle size agglomeration. The ZnO-NPs exhibited antibacterial activity against several bacterial strains isolated from animal wounds, including <i>Staphylococcus aureus</i>, <i>Staphylococcus epidermidis</i>, <i>Escherichia coli</i>, <i>Pseudomonas aeruginosa</i>, and <i>Klebsiella pneumoniae</i>, with inhibition zones ranging from 10.0 to 24.5 mm, average MIC values ranging from 1.87 ± 0.36 to 3.12 ± 0.62 mg/mL, and an optimum inhibitory effect against <i>Staphylococcus</i> spp. The time-kill kinetic assay revealed that the Zn-ONPs eradicated <i>Staphylococcus</i> spp. and <i>Klebsiella pneumoniae</i>, as well as <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i> (99.9% or 3-log10 reduction), within 30 min of treatment. They also demonstrated a varying degree of antibiofilm formation activity, as indicated by the percentage reduction in biofilm formation compared to the untreated biofilm-forming bacterial strains. <b>Conclusion:</b> ZnO-NPs effectively inhibit bacterial growth and biofilm formation in animal wound isolates.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503282","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":"Nanoparticles for Thrombolytic Therapy in Ischemic Stroke: A Systematic Review and Meta-Analysis of Preclinical Studies.","authors":"Jesús Prego-Domínguez, Fernando Laso-García, Nuria Palomar-Alonso, María Pérez-Mato, Esteban López-Arias, Antonio Dopico-López, Pablo Hervella, María Gutiérrez-Fernández, María Alonso de Leciñana, Ester Polo, Beatriz Pelaz, Pablo Del Pino, Francisco Campos, Clara Correa-Paz","doi":"10.3390/pharmaceutics17020208","DOIUrl":"https://doi.org/10.3390/pharmaceutics17020208","url":null,"abstract":"<p><p><b>Background:</b> Recombinant tissue plasminogen activator (rtPA) remains the standard thrombolytic treatment for ischemic stroke. Different types of nanoparticles have emerged as promising tools to improve the benefits and decrease the drawbacks of this therapy. Among them, cell membrane-derived (CMD) nanomedicines have gained special interest due to their capability to increase the half-life of particles in blood, biocompatibility, and thrombus targeting. In order to update and evaluate the efficacy of these nanosystems, we performed a meta-analysis of the selected in vivo preclinical studies. <b>Methods:</b> Preclinical in vivo studies in ischemic stroke models have been identified through a search in the Pubmed database. We included studies of rtPA-nanoparticles, which assessed infarct volume and/or neurological improvement. Nanosystems were compared with free (non-encapsulated) rtPA treatment. Standardized mean differences were computed and pooled to estimate effect sizes for lesion volumes and neurological scores. Subgroup analyses by the risk of bias, type of nanoparticle, and time of administration were also performed. <b>Results:</b> A total of 18 publications were included in the meta-analysis. This was based on defined search inclusion criteria. Our analysis revealed that rtPA-nanoparticles improved both lesion volume and neurological scores compared with the free rtPA treatment. Moreover, CMD nanomedicines showed better evolution of infarct volume compared to the other nanoparticles. Funnel plots of lesion volume exhibited asymmetry and publication bias. Heterogeneity was generally high, and the funnel plot and Egger test showed some evidence of publication bias that did not achieve statistical significance in the trim-and-fill analysis. <b>Conclusions:</b> rtPA-encapsulating nanosystems were shown to decrease infarct volume and improve neurological scales compared to the standard treatment, and CMD nanomedicines had the greatest beneficial effect.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503368","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":"Nanostructured Formulations for a Local Treatment of Cancer: A Mini Review About Challenges and Possibilities.","authors":"Tatiane Roquete Amparo, Tamires Cunha Almeida, Lucas Resende Dutra Sousa, Viviane Flores Xavier, Glenda Nicioli da Silva, Geraldo Célio Brandão, Orlando David Henrique Dos Santos","doi":"10.3390/pharmaceutics17020205","DOIUrl":"https://doi.org/10.3390/pharmaceutics17020205","url":null,"abstract":"<p><p>Cancer represents a significant societal, public health, and economic challenge. Conventional chemotherapy is based on systemic administration; however, it has current limitations, including poor bioavailability, high-dose requirements, adverse side effects, low therapeutic indices, and the development of multiple drug resistance. These factors underscore the need for innovative strategies to enhance drug delivery directly to tumours. However, local treatment also presents significant challenges, including the penetration of the drug through endothelial layers, tissue density in the tumour microenvironment, tumour interstitial fluid pressure, physiological conditions within the tumour, and permanence at the site of action. Nanotechnology represents a promising alternative for addressing these challenges. This narrative review elucidates the potential of nanostructured formulations for local cancer treatment, providing illustrative examples and an analysis of the advantages and challenges associated with this approach. Among the nanoformulations developed for the local treatment of breast, bladder, colorectal, oral, and melanoma cancer, polymeric nanoparticles, liposomes, lipid nanoparticles, and nanohydrogels have demonstrated particular efficacy. These systems permit mucoadhesion and enhanced tissue penetration, thereby increasing the drug concentration at the tumour site (bioavailability) and consequently improving anti-tumour efficacy and potentially reducing adverse effects. In addition to studies indicating chemotherapy, nanocarriers can be used as a theranostic approach and in combination with irradiation methods.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503378","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":"Impact of Co-Spray Drying with Leucine or Trileucine on Aerosol Performance, In Vitro Dissolution, and Cellular Uptake of Colistin Powder Formulations for Inhalation.","authors":"Yijing Huang, Kinnari Santosh Arte, Chanakya D Patil, Qi Zhou, Li Qu","doi":"10.3390/pharmaceutics17020199","DOIUrl":"https://doi.org/10.3390/pharmaceutics17020199","url":null,"abstract":"<p><p><b>Background/Objective</b>: Surface enrichment of hydrophobic excipients via spray drying has been demonstrated as an efficient way to protect the dry powder inhaler formulations against moisture-induced deterioration in aerosol performance. However, the impact of such surface enrichment on dissolution and cellular uptake is less investigated, which can affect the safety and efficacy of dry powder inhalers (DPIs). <b>Methods</b>: In the present work, hygroscopic colistin was coated with leucine or trileucine, at different weight ratios during spray drying. All the powders were exposed to 75% relative humidity for one week. The aerosol performance was compared before and after the moisture exposure. Various solid-state characterizations, including particle size, particle morphology, crystallinity, water sorption/desorption, and surface composition, were conducted to evaluate the properties of spray-dried colistin with/without leucine or trileucine. <b>Results</b>: The results indicated that leucine or trileucine could protect the aerosol performance of spray-dried colistin against moisture deterioration. Leucine crystallized after spray drying with colistin, and such crystal leucine could further hinder water uptake when leucine was at a 20% or higher weight ratio. Trileucine did not crystallize after spray drying with colistin nor reduce the water uptake. Interestingly, trileucine showed a superior moisture protective effect to that of leucine, which could be attributed to its better surface enrichment efficiency than that of leucine due to its lower water solubility. <b>Conclusions</b>: Importantly, our results showed that the surface enrichment with leucine and trileucine did not significantly affect in vitro dissolution of colistin in the Franz cell test and cellular uptake of colistin in the H441 lung epithelium cell model, which could be attributed to small particle size and incomplete surface coverage by leucine or trileucine.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503295","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":"Subcellular Organelle Targeting as a Novel Approach to Combat Tumor Metastasis.","authors":"Zefan Liu, Yang Liu, Xin Kang, Lian Li, Yucheng Xiang","doi":"10.3390/pharmaceutics17020198","DOIUrl":"https://doi.org/10.3390/pharmaceutics17020198","url":null,"abstract":"<p><p>Tumor metastasis, the spread of cancer cells from the primary site to distant organs, remains a formidable challenge in oncology. Central to this process is the involvement of subcellular organelles, which undergo significant functional and structural changes during metastasis. Targeting these specific organelles offers a promising avenue for enhanced drug delivery and metastasis therapeutic efficacy. This precision increases the potency and reduces potential off-target effects. Moreover, by understanding the role of each organelle in metastasis, treatments can be designed to disrupt the metastatic process at multiple stages, from cell migration to the establishment of secondary tumors. This review delves deeply into tumor metastasis processes and their connection with subcellular organelles. In order to target these organelles, biomembranes, cell-penetrating peptides, localization signal peptides, aptamers, specific small molecules, and various other strategies have been developed. In this review, we will elucidate targeting delivery strategies for each subcellular organelle and look forward to prospects in this domain.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503342","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":"Modulating Polyphenol Activity with Metal Ions: Insights into Dermatological Applications.","authors":"Oana Cioanca, Ionut-Iulian Lungu, Denisa Batir-Marin, Andreea Lungu, George-Alexandru Marin, Riana Huzum, Alina Stefanache, Nazim Sekeroglu, Monica Hancianu","doi":"10.3390/pharmaceutics17020194","DOIUrl":"https://doi.org/10.3390/pharmaceutics17020194","url":null,"abstract":"<p><strong>Background: </strong>The skin represents the first barrier of defense, and its integrity is crucial for overall health. Skin wounds present a considerable risk seeing how their progression is rapid and sometimes they are caused by comorbidities like diabetes and venous diseases. Nutraceutical combinations like the ones between polyphenols and metal ions present considerable applications thanks to their increased bioavailability and their ability to modulate intrinsic molecular pathways.</p><p><strong>Methods: </strong>The research findings presented in this paper are based on a systematic review of the current literature with an emphasis on nanotechnology and regenerative medicine strategies that incorporate polyphenols and metallic nanoparticles (NPs). The key studies which described the action mechanisms, efficacy, and safety of these hybrid formulations were reviewed.</p><p><strong>Results: </strong>Nanocomposites of polyphenol and metal promote healing by activating signaling pathways such as PI3K/Akt and ERK1/2, which in turn improve fibroblast migration and proliferation. Nanoparticles of silver and copper have antibacterial, angiogenesis-promoting, inflammation-modulating capabilities. With their ability to induce apoptosis and restrict cell growth, these composites have the potential to cure skin malignancies in addition to facilitating wound healing.</p><p><strong>Conclusions: </strong>Nanocomposites of polyphenols and metals provide hope for the treatment of cancer and chronic wounds. Their antimicrobial capabilities, capacity to modulate inflammatory responses, and enhancement of fibroblast activity all point to their medicinal potential. Furthermore, these composites have the ability to decrease inflammation associated with tumors while simultaneously inducing cell death in cancer cells. Clarifying their mechanisms, guaranteeing stability, and enhancing effective delivery techniques for clinical usage should be the focus of future studies.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503361","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}