Pharmaceutics最新文献

{"title":"Revolutionizing Drug Delivery: The Impact of Advanced Materials Science and Technology on Precision Medicine.","authors":"Mohamed El-Tanani, Shakta Mani Satyam, Syed Arman Rabbani, Yahia El-Tanani, Alaa A A Aljabali, Ibrahim Al Faouri, Abdul Rehman","doi":"10.3390/pharmaceutics17030375","DOIUrl":"10.3390/pharmaceutics17030375","url":null,"abstract":"<p><p>Recent progress in material science has led to the development of new drug delivery systems that go beyond the conventional approaches and offer greater accuracy and convenience in the application of therapeutic agents. This review discusses the evolutionary role of nanocarriers, hydrogels, and bioresponsive polymers that offer enhanced drug release, target accuracy, and bioavailability. Oncology, chronic disease management, and vaccine delivery are some of the applications explored in this paper to show how these materials improve the therapeutic results, counteract multidrug resistance, and allow for sustained and localized treatments. The review also discusses the translational barriers of bringing advanced materials into the clinical setting, which include issues of biocompatibility, scalability, and regulatory approval. Methods to overcome these challenges include surface modifications to reduce immunogenicity, scalable production methods such as microfluidics, and the harmonization of regulatory systems. In addition, the convergence of artificial intelligence (AI) and machine learning (ML) is opening new frontiers in material science and personalized medicine. These technologies allow for predictive modeling and real-time adjustments to optimize drug delivery to the needs of individual patients. The use of advanced materials can also be applied to rare and underserved diseases; thus, new strategies in gene therapy, orphan drugs development, and global vaccine distribution may offer new hopes for millions of patients.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720972","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":"N-(9-Acridinyl) Amino Acid Derivatives: Synthesis and In Vitro Evaluation of Anti-<i>Toxoplasma gondii</i> Activity.","authors":"Đorđe Zlatković, Vladimir Dobričić, Jelena Srbljanović, Olivera Lijeskić, Neda Bauman, Vladimir Ćirković, Tijana Štajner","doi":"10.3390/pharmaceutics17030374","DOIUrl":"10.3390/pharmaceutics17030374","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Acridine, an aromatic heterocyclic compound, serves as a basis for the synthesis of potent bioactive derivatives, displaying a broad spectrum of biological activity, such as antibacterial, antitumor, and antiparasitic activity. With the ability to undergo various types of electrophilic substitutions, introducing different side chains could lead to compounds being active towards various and potentially multiple biotargets. <i>Toxoplasma gondii</i>, a ubiquitous protozoan parasite with worldwide distribution, poses a major health threat, particularly in immunocompromised patients and fetuses. Current treatment options for toxoplasmosis are scarce, with notable limitations, especially regarding side myelotoxicity and inactivity towards <i>T. gondii</i> cysts, causing a need for novel drug candidates. The aim of this study was to evaluate selected N-(9-acrydinil) amino acid derivatives as potential anti-<i>T. gondii</i> agents. <b>Methods</b>: Synthesis of new derivatives was performed using a two-step method, with the initial mixing of 9-chloroacridine with methanol and sodium alkoxide solution and subsequent adding of appropriate amino acids. Cytotoxicity of the tested compounds was evaluated on the Vero cell line using a MTT assay, while their anti-<i>T. gondii</i> activity was investigated using <i>T. gondii</i> RH strain tachyzoites. <b>Results</b>: CC₅₀ values of the derivatives ranged from 41.72 to 154.10 µM. Anti-<i>T. gondii</i> activity, displayed as a reduction in the number of viable tachyzoites compared to the untreated control, ranged from 0 to 33.3%. One of the derivatives displayed activity comparable to the standard treatment option while retaining acceptable cytotoxicity. Esterification, presence of aromatic substituents and the length of the amino acid side chain were identified as key factors that affect both toxicity and activity of these derivatives. <b>Conclusions</b>: Promising results obtained throughout this study provide guidelines for further structural modifications of N-(9-acrydinil) amino acid derivatives in order to synthesize drug candidates competitive to standard treatment options for toxoplasmosis.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720945","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":"Correction: Kuskov et al. Amphiphilic Poly-<i>N</i>-vinylpyrrolidone Nanoparticles as Carriers for Nonsteroidal, Anti-Inflammatory Drugs: Pharmacokinetic, Anti-Inflammatory, and Ulcerogenic Activity Study. <i>Pharmaceutics</i> 2022, <i>14</i>, 925.","authors":"Andrey Kuskov, Dragana Nikitovic, Aikaterini Berdiaki, Mikhail Shtilman, Aristidis Tsatsakis","doi":"10.3390/pharmaceutics17030369","DOIUrl":"10.3390/pharmaceutics17030369","url":null,"abstract":"<p><p><b>Error in Figure</b> [...].</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721015","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":"Development and Evaluation of Fluconazole Co-Crystal for Improved Solubility and Mechanical Properties.","authors":"Ritu Rathi, Inderbir Singh, Tanikan Sangnim, Kampanart Huanbutta","doi":"10.3390/pharmaceutics17030371","DOIUrl":"10.3390/pharmaceutics17030371","url":null,"abstract":"<p><p><b>Background</b>: Fluconazole (FLZ) is a broad-spectrum anti-fungal drug presenting poor flowability, mechanical properties, and limited aqueous solubility. These issues pose challenges for the handling and manufacturing of dosage forms of FLZ. The current research aimed to develop fluconazole co-crystal (CC) for improving its aqueous solubility, flowability, and mechanical properties. (2) <b>Methods:</b> The fluconazole benzoic acid (FLZ-BA) co-crystal was prepared using the solvent evaporation technique. The prepared co-crystal was characterized for drug content, solubility, anti-fungal activity, dissolution, and stability. DSC (Differential Scanning Calorimetry), PXRD (Powder X-Ray Diffraction), SEM (Scanning Electron Microscopy), and FTIR (Fourier Transmission Infrared) spectroscopy were carried out to confirm the co-crystal formation. The co-crystal was further evaluated for their flow characteristics and mechanical properties via CTC (compressibility, tabletability, and compactibility), Heckel, and Kawakita analysis. (3) <b>Results</b>: The CC showed 69.51% drug content and 13-fold greater aqueous solubility than pure FLZ. The DSC thermogram showed a sharp endothermic peak between the parent components, a distinct PXRD pattern was observed, and the SEM analysis revealed a different morphology, confirming the formation of co-crystal (new crystalline form). The CC showed immediate drug release and was found to more stable, and less hygroscopic than FLZ alone. The CC revealed better flowability, tabletability (tensile strength), compressibility, and compactibility. Moreover, Heckel and Kawakita analysis indicated the co-crystal to deform plastically, favoring improved compression. (4) <b>Conclusions</b>: The immediate drug release capabilities, improved hygroscopic stability, solubility, better antifungal activity, and flowability make FLZ-BA co-crystal a suitable candidate for the preparation of an immediate drug release dosage form. The study also revealed the application of co-crystal for improving the flowability and mechanical properties.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720740","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":"Physiologically Based Pharmacokinetic Models for Infliximab, Ipilimumab, and Nivolumab Developed with GastroPlus to Predict Hepatic Concentrations.","authors":"Celeste Vallejo, Cameron Meaney, Lara Clemens, Kyunghee Yang, Viera Lukacova, Haiying Zhou","doi":"10.3390/pharmaceutics17030372","DOIUrl":"10.3390/pharmaceutics17030372","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Infliximab, ipilimumab, and nivolumab are three monoclonal antibodies that have been associated with hepatotoxicity. Three separate physiologically based pharmacokinetic (PBPK) models were developed in GastroPlus^® to simulate plasma and liver concentrations in patient populations after administration of either infliximab, ipilimumab, or nivolumab. <b>Methods:</b> The models include distribution and clearance mechanisms specific to large molecules, FcRn binding dynamics, and target-mediated drug disposition (TNF-α for infliximab, CTLA-4 for ipilimumab, and PD-1 for nivolumab). <b>Results:</b> The PBPK model for each large molecule was able to reproduce observed plasma concentration data in patient populations, including patients with rheumatoid arthritis and patients with solid tumors. Liver concentrations were predicted to be between 10% and 23% of the plasma concentrations for each of the three drugs, aligning with previously reported results. This lends further validity to the PBPK models and their ability to accurately predict hepatic concentrations in the absence of direct tissue measurements. <b>Conclusions:</b> These results can be used to drive liver toxicity predictions using the quantitative systems toxicology model, BIOLOGXsym™, which integrates hepatic interstitial concentrations with in vitro mechanistic toxicity data to predict the extent of liver toxicity for biologics.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721054","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":"Improved Photodynamic Therapy of Hepatocellular Carcinoma via Surface-Modified Protein Nanoparticles.","authors":"Ahmed M Abdelsalam, Amir Balash, Shaimaa M Khedr, Muhammad Umair Amin, Konrad H Engelhardt, Eduard Preis, Udo Bakowsky","doi":"10.3390/pharmaceutics17030370","DOIUrl":"10.3390/pharmaceutics17030370","url":null,"abstract":"<p><p><b>Background:</b> Photodynamic therapy (PDT) has evolved as a reliable therapeutic modality for cancer. However, the broad application of the technique is still limited because of poor bioavailability and the non-selective distribution of photosensitizers within host tissues. Herein, zein, a natural corn protein, was functionalized with glycyrrhetinic acid (GA) and polyethylene glycol (Z-PEG-GA) as a targeting platform for liver cancer cells. Parietin, as novel photosensitizer, was successfully encapsulated into zein via nanoprecipitation and used for the therapy of hepatocellular carcinoma. <b>Methods:</b> The in vitro phototoxicity of Z-PEG-GA nanoparticles and their non-functionalized control (Z-PEG) were assessed against hepatocellular carcinoma (HepG2 cells) and the In vivo biodistribution was determined in an adult male CD-1 Swiss albino mice model. <b>Results:</b> The formulated Z-PEG and Z-PEG-GA showed spherical shapes with average sizes of 82.8 and 94.7 nm for unloaded nanoparticles, respectively, and 109.7 and 111.5 nm for loaded nanoparticles carrying more than 70% of parietin, and Quantum yield measurements show that parietin's photodynamic potential is conserved. Moreover, parietin-loaded Z-PEG-GA exhibited three-fold higher toxicity against liver cancer cells than its non-functionalized control and attained more than an eleven-fold enhancement in the generated intracellular reactive oxygen species (ROS) at a 9 J/cm² radiant exposure. The generated intracellular ROS led to mitochondrial disruption and the release of cytochrome c. In vivo biodistribution studies revealed that fluorescence signals of Z-PEG-GA can persist in the excised animal liver for up to 24 h post-administration. <b>Conclusions:</b> Consequently, tailored zein can hold great potential for delivering several hydrophobic photosensitizers in anticancer PDT.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Influence of Indisulam on Human Immune Effector Cells: Is a Combination with Immunotherapy Feasible?","authors":"Lisa Arnet, Lisabeth Emilius, Annett Hamann, Maria Carmo-Fonseca, Carola Berking, Jan Dörrie, Niels Schaft","doi":"10.3390/pharmaceutics17030368","DOIUrl":"10.3390/pharmaceutics17030368","url":null,"abstract":"<p><p><b>Background:</b> As a modulator of pre-mRNA splicing, the anti-cancer agent indisulam can induce aberrantly spliced neoantigens, enabling immunologic anti-tumor activity. Consequently, combining indisulam with immunotherapy is expected to be a promising novel approach in cancer therapy. However, a prerequisite for such a combination is that immune effector cells remain functional and unharmed by the chemical. <b>Methods:</b> To ensure the immunocompetence of human immune effector cells is maintained, we investigated the influence of indisulam on ex vivo-isolated T cells and monocyte-derived dendritic cells (moDCs) from healthy donors. We used indisulam concentrations from 0.625 µM to 160 µM and examined the impact on the following: (i) the activation of CD4⁺ and CD8⁺ T cells by CD3-crosslinking and via a high-affinity TCR, (ii) the cytotoxicity of CD8⁺ T cells, (iii) the maturation process of moDCs, and (iv) antigen-specific CD8⁺ T cell priming. <b>Results:</b> We observed dose-dependent inhibitory effects of indisulam, and substantial inhibition occurred at concentrations around 10 µM, but the various functions of the immune system exhibited different sensitivities. The weaker activation of T cells via CD3-crosslinking was more sensitive than the stronger activation via the high-affinity TCR. T cells remained capable of killing tumor cells after treatment with indisulam up to 40 µM, but T cell cytotoxicity was impaired at 160 µM indisulam. While moDC maturation was also rather resistant, T cell priming was almost completely abolished at a concentration of 10 µM. <b>Conclusions:</b> These effects should be considered in possible future combinations of immunotherapy with the mRNA splicing inhibitor indisulam.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720929","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":"Leveraging Omeprazole PBPK/PD Modeling to Inform Drug-Drug Interactions and Specific Recommendations for Pediatric Labeling.","authors":"Amira Soliman, Leyanis Rodriguez-Vera, Ana Alarcia-Lacalle, Leandro F Pippa, Saima Subhani, Viera Lukacova, Jorge Duconge, Natalia V de Moraes, Valvanera Vozmediano","doi":"10.3390/pharmaceutics17030373","DOIUrl":"10.3390/pharmaceutics17030373","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Omeprazole is widely used for managing gastrointestinal disorders like GERD, ulcers, and <i>H. pylori</i> infections. However, its use in pediatrics presents challenges due to drug interactions (DDIs), metabolic variability, and safety concerns. Omeprazole's pharmacokinetics (PK), primarily influenced by CYP2C19 metabolism, is affected by ontogenetic changes in enzyme expression, complicating dosing in children. <b>Methods</b>: This study aimed to develop and validate a physiologically based pharmacokinetic (PBPK) model for omeprazole and its metabolites to predict age-related variations in metabolism and response. <b>Results</b>: The PBPK model successfully predicted exposure to parent and metabolites in adults and pediatrics, incorporating competitive and mechanism-based inhibition of CYP2C19 and CYP3A4 by omeprazole and its metabolites. By accounting for age-dependent metabolic pathways, the model enabled priori predictions of omeprazole exposure in different age groups. Linking PK to the pharmacodynamics (PD) model, we described the impact of age-related physiological changes on intragastric pH, the primary outcome for proton pump inhibitors efficacy. <b>Conclusions</b>: The PBPK-PD model allowed for the virtual testing of dosing scenarios, providing an alternative to clinical studies in pediatrics where traditional DDI studies are challenging. This approach offers valuable insights for accurate dosing recommendations in pediatrics, accounting for age-dependent variability in metabolism, and underscores the potential of PBPK modeling in guiding pediatric drug development.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720365","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":"Therapeutic Efficacy of Small Extracellular Vesicles Loaded with ROCK Inhibitor in Parkinson's Disease.","authors":"Candy Carbajal, Myosotys Rodriguez, Florida Owens, Nicole Stone, Dileepkumar Veeragoni, Rebecca Z Fan, Kim Tieu, Nazira El-Hage","doi":"10.3390/pharmaceutics17030365","DOIUrl":"10.3390/pharmaceutics17030365","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Parkinson's disease (PD) is a rapidly growing neurological disorder in the developed world, affecting millions over the age of 60. The decline in motor functions occurs due to a progressive loss of midbrain dopaminergic neurons, resulting in lowered dopamine levels and impaired muscle function. Studies show defective mitochondrial autophagy (or \"mitophagy\") links to PD. Rho-associated coiled-coil containing protein kinases (ROCK) 1 and ROCK2 are serine/threonine kinases, and their inhibition can enhance neuroprotection in PD by promoting mitophagy. <b>Methods:</b> We examine the effects of ROCK inhibitor SR3677, delivered via macrophage-derived small extracellular vesicles (sEVs) to Parkin Q311X(A) PD mouse models. sEVs with SR3677, administered intranasally, increased mitophagy gene expression, reduced inflammatory factors, and elevated dopamine levels in brain tissues. <b>Results:</b> ROCK2 expression decreased, showing the drug's inhibitory effect. sEV-SR3677 treatment was more effective than treatment with the drug alone, although sham EVs showed lower effects. This suggests that EV-SR3677 not only activates mitochondrial processes but also promotes the degradation of damaged mitochondria through autophagy. Mitochondrial functional assays and oxygen consumption in ex vivo glial cultures revealed that sEV-SR3677 significantly improved mitochondrial respiration compared to that in untreated or SR3677-only treated cells. <b>Conclusion:</b> We demonstrated the efficacy of ROCK2 inhibition on mitochondrial function via sEV-SR3677 in the PD mouse model, necessitating further studies to explore design challenges and mechanisms of sEV-SR3677 as mitochondria-targeted therapy for PD.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721007","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":"Nasal Administration of a Nanoemulsion Based on Methyl Ferulate and Eugenol Encapsulated in Chitosan Oleate: Uptake Studies in the Central Nervous System.","authors":"Giada Botti, Laura Catenacci, Alessandro Dalpiaz, Luca Randi, Maria Cristina Bonferoni, Sara Perteghella, Sarah Beggiato, Luca Ferraro, Barbara Pavan, Milena Sorrenti","doi":"10.3390/pharmaceutics17030367","DOIUrl":"10.3390/pharmaceutics17030367","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The phytochemicals ferulic acid (Fer) and eugenol display neuroprotective effects for their anti-oxidative properties; moreover, eugenol can induce dopamine (DA) release from dopaminergic neuronal cells. However, poor bioavailability and/or fast elimination rate limit their clinical benefits. We therefore propose a new nasal formulation based on a nanoemulsion (NE) for the jointed brain-targeting of eugenol and methyl ferulate (Fer-Me, i.e., a Fer-lipidized derivative maintaining the parent compound anti-oxidative properties). NE was obtained using chitosan oleate, a surfactant combining mucoadhesive and absorption-enhancing properties with stabilizing effects on the dispersion of eugenol, used as a Fer-Me vehicle. <b>Methods</b>: The nasal formulation was obtained by spontaneous emulsification processes; cell viability and uptake studies were performed on an in vitro model of respiratory mucosa (RPMI 2650 cells). After intravenous and nasal administrations, the pharmacokinetic profiles of eugenol and Fer-Me in rats' bloodstreams and cerebrospinal fluid (CSF) were analyzed via HPLC-UV analysis. <b>Results</b>: The NE dispersed-phase mean diameter was 249.22 ± 32.78 nm; Fer-Me and eugenol loading in NE was about 1 and 2 mg/mL, respectively. NE increased the uptake of loaded compounds by mucosal cells. Following intravenous administration, the Fer-Me plasma half-life was 10.08 ± 0.37 min, and a negligible ability of the compound to permeate in the CSF, compared to eugenol, was observed. NE nasal administration allowed us to sensibly increase the Fer-Me brain-targeting and prolong the eugenol permanence in the CSF. <b>Conclusions</b>: This nasal formulation appears promising to overcome Fer and eugenol pharmacokinetic issues. The possible translational relevance of the present findings is discussed.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721030","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}