Pharmaceutics最新文献

{"title":"Stabilization of Self-Pressurized Gelatin Capsules for Oral Delivery of Biologics.","authors":"Amy J Wood-Yang, Joshua I Palacios, Abishek Sankaranarayanan, Mark R Prausnitz","doi":"10.3390/pharmaceutics17091156","DOIUrl":"10.3390/pharmaceutics17091156","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Oral delivery of biologics offers advantages for patient access and adherence compared to injection, but suffers from low bioavailability due to mucosal barriers and drug degradation in the gastrointestinal tract. We previously developed an oral self-pressurized aerosol (OSPRAE) capsule that uses effervescent excipients to generate CO₂ gas, building internal pressure to eject powdered drug at high velocity across intestinal mucosa. <b>Methods:</b> Here, we developed two key design improvements: (i) an enteric covering to protect the capsule delivery orifice in gastric fluids and (ii) reduced humidity content of capsules to extend shelf-life. <b>Results:</b> Enteric-covered capsules prevented drug release in simulated gastric fluid and then enabled rapid release upon transfer to simulated intestinal fluid. Burst pressure for enteric-covered capsules was ~3-4 times higher than non-covered capsules. After storage for up to three days, the capsules' effervescent excipients pre-reacted, making them unable to achieve high pressure during subsequent use. To address this limitation, we prepared capsules under reduced humidity conditions, which inhibited pre-reaction of effervescent excipients during storage, and a polyurethane coating to improve water uptake into the capsule to drive the effervescence reaction in intestinal fluid. <b>Conclusions:</b> These design improvements enable improved functionality of OSPRAE capsules for continued translation in pre-clinical and future clinical development.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177475","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":"Selenium Nanoparticles: Synthesis, Stability and In Vitro Evaluation in Human Lens Epithelial Cells.","authors":"Lulwah Al-Bassam, Mohammed M Naiyer, Christopher J Morris, Steve Brocchini, Gareth R Williams","doi":"10.3390/pharmaceutics17091157","DOIUrl":"10.3390/pharmaceutics17091157","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Oxidative stress plays a critical role in the development of ocular diseases such as cataracts. Selenium nanoparticles (SeNPs) offer antioxidant benefits with low toxicity. This study aimed to evaluate the antioxidant activity of SeNPs coated with D-α-tocopheryl polyethylene glycol succinate (TPGS) in human lens epithelial (HLE) cells. <b>Methods</b>: SeNPs were synthesised by reducing sodium selenite with ascorbic acid in the presence of TPGS. Physicochemical characterisation was carried out using dynamic light scattering to assess size and surface charge. Antioxidant activity was measured by a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Cytocompatibility was assessed on adult retinal pigment epithelial (ARPE-19) and HLE cells using PrestoBlue. Functional antioxidant performance was determined through enzymatic assays for glutathione peroxidase (GPx), thioredoxin reductase (TrxR), and glutathione (GSH), and lipid peroxidation was assessed using malondialdehyde (MDA) quantification. Catalase mimicry was evaluated under 3-amino-1,2,4-triazole (3-AT)-induced inhibition. <b>Results</b>: The optimal SeNP formulation had an average hydrodynamic diameter of 44 ± 3 nm, low PDI (<0.1), and a surface charge of -15 ± 3 mV. These TPGS-SeNPs demonstrated strong radical scavenging (EC₅₀ ≈ 1.55 µg/mL) and were well tolerated by ARPE-19 cells (IC₅₀ = 524 µg/mL), whereas HLE cells had a narrower biocompatibility window (≤0.4 µg/mL, IC₅₀ = 2.2 µg/mL). Under oxidative stress, SeNPs significantly enhanced GPx and TrxR activity but did not affect GSH or MDA levels. No catalase-mimetic activity was observed. <b>Conclusions</b>: TPGS-SeNPs exhibit potent antioxidant enzyme modulation under stress conditions in HLE cells. Although not affecting all oxidative markers, these nanoparticles show promise for non-invasive strategies targeting lens-associated oxidative damage, including cataract prevention.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177472","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":"Advances in Gold Nanoparticles for the Diagnosis and Management of Alzheimer's Disease.","authors":"Bhagavathi Sundaram Sivamaruthi, Periyanaina Kesika, Natarajan Sisubalan, Chaiyavat Chaiyasut","doi":"10.3390/pharmaceutics17091158","DOIUrl":"10.3390/pharmaceutics17091158","url":null,"abstract":"<p><p>Alzheimer's disease (AD) presents a significant challenge in modern healthcare, prompting exploration into novel therapeutic strategies. This review clearly classifies different types of gold (Au) nanoparticles (NPs) (AuNPs), links them to the gut-brain axis, highlights recent advances, and points out future research needs, offering a more updated perspective than earlier reviews. Diverse approaches have emerged from single to hybrid and functionalized AuNPs, including innovative nanotherapeutic agents like Au nanorods-polyethylene glycol-angiopep-2 peptide/D1 peptide and noninvasive dynamic magnetic field-stimulated NPs. AuNPs have been reported for the neuroprotective properties. Clinical applications of AuNPs highlight their promise in diagnosis and therapeutic monitoring. However, challenges persist, notably in overcoming blood-brain barrier limitations and refining drug delivery systems. Furthermore, the incomplete understanding of AD's physiological and pathological mechanisms hinders therapeutic development. Future research directions should prioritize elucidating these mechanisms and optimizing AuNPs physicochemical properties for therapeutic efficacy. Despite limitations, nanomaterial-based therapies hold promise for revolutionizing AD treatment and addressing other central nervous system disorders. It also emphasizes the importance of further investigation into the potential of AuNPs, envisioning a future where they serve as a cornerstone in advancing neurological healthcare.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177375","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":"Strategic Objectives of Nanotechnology-Driven Repurposing in Radiopharmacy-Implications for Radiopharmaceutical Repurposing (Beyond Oncology).","authors":"María Jimena Salgueiro, Marcela Zubillaga","doi":"10.3390/pharmaceutics17091159","DOIUrl":"10.3390/pharmaceutics17091159","url":null,"abstract":"<p><p>The integration of nanotechnology into drug repurposing strategies is redefining the development landscape for diagnostic, therapeutic, and theranostic agents. In radiopharmacy, nanoplatforms are increasingly being explored to enhance or extend the use of existing radiopharmaceuticals, complementing earlier applications in other biomedical fields. Many of these nanoplatforms evolve into multifunctional systems by incorporating additional imaging modalities (e.g., MRI, fluorescence) or non-radioactive therapies (e.g., photodynamic therapy, chemotherapy). These hybrid constructs often emerge from the reformulation, repositioning, or revival of previously approved or abandoned compounds, generating entities with novel pharmacological, pharmacokinetic, and biodistribution profiles. However, their translational potential faces significant regulatory hurdles. Existing frameworks-typically designed for single-modality drugs or devices-struggle to accommodate the combined complexity of nanoengineering, radioactive components, and integrated functionalities. This review examines how these systems challenge current norms in classification, safety assessment, preclinical modeling, and regulatory coordination. It also addresses emerging concerns around digital adjuncts such as AI-assisted dosimetry and software-based therapy planning. Finally, the article outlines international initiatives aimed at closing regulatory gaps and provides future directions for building harmonized, risk-adapted frameworks that support innovation while ensuring safety and efficacy.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176590","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":"Drug Metabolism and Pharmacokinetics of Oxazolo[4,5-<i>c</i>]quinoline Analogs as Novel Interleukin-33 Inhibitors.","authors":"Hayoung Jeon, Geonhee Jang, Min-A Ban, Sang-Hyun Son, Youngjoo Byun, Kiho Lee","doi":"10.3390/pharmaceutics17091153","DOIUrl":"10.3390/pharmaceutics17091153","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Interleukin-33 (IL-33) is crucial in immune-mediated diseases like asthma. Targeting the IL-33/ST2 pathway holds therapeutic promise. This study characterized the pharmacokinetics (PK) and metabolism of KB-1517 and KB-1518, new oxazolo[4,5-<i>c</i>]quinoline IL-33 inhibitors. <b>Methods</b>: PK studies were conducted in male ICR mice following intravenous (IV) and oral (PO) administration. In vitro metabolic stability and metabolite identification were assessed using human and mouse liver S9 fractions supplemented with cofactors (NADPH, UDPGA, PAPS, GSH). Plasma and incubation samples were analyzed using validated LC-MS/MS methods. <b>Results</b>: KB-1517 exhibited slow absorption/elimination and high apparent oral bioavailability (>100%) post-PO, with an unusually late increase in plasma concentration after IV dosing, hindering terminal parameter calculation. KB-1518 showed low clearance post-IV but suffered from low oral bioavailability (~14%). Both compounds demonstrated high in vitro metabolic stability (t_½ > 60 min) in both human and mouse liver S9 fractions. Primary metabolism involved phase I oxidation (N-oxidation and N-demethylation), yielding several metabolites identified in vitro and confirmed in vivo. Some species differences in metabolite profiles were observed. <b>Conclusions</b>: KB-1517 and KB-1518 are promising, metabolically stable IL-33 inhibitor lead compounds with distinct PK profiles. KB-1517's complex kinetics suggest potential sustained exposure but require further elucidation. KB-1518's low oral bioavailability necessitates further optimization. These ADME findings provide a critical foundation for their continued optimization and development.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177463","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":"Oral Tablet Formulations with Lactoferrin, a Cohesive Biomacromolecule.","authors":"True L Rogers, Andrew J Horton, Thomas Watson, Stephanie Robart, Brooklynn DeFrancesco, Hannah Bishop, Elizabeth Tocce","doi":"10.3390/pharmaceutics17091151","DOIUrl":"10.3390/pharmaceutics17091151","url":null,"abstract":"<p><p><b>Background/Objectives:</b> The aim of our research was to understand how excipients, unit operations, and process parameters impact processability and resulting properties, performance, and stability of tablets containing bovine lactoferrin, a cohesive biomacromolecule. <b>Methods:</b> Microcrystalline cellulose (MCC), croscarmellose (xCMC), lactose (LAC), hydroxypropyl methylcellulose (HPMC), and sodium stearyl fumarate (SSF) were used to produce various tablet formulations containing lactoferrin across a concentration range of 5 to 45%, targeting immediate- or controlled release performance. Tablets were made either by direct compression or via dry granulation followed by tableting. In addition to release performance, tablet attributes were characterized for tensile strength, friability, weight uniformity, and content uniformity. <b>Results:</b> Acceptable tablet tensile strength, friability, and performance were obtained for lactoferrin concentrations ranging from 15 to 45%, using a variety of excipients and manufacturing approaches. In several cases, dry granulation improved content uniformity. Excipient choice and tablet compression force impacted drug release, particularly when MCC alone was used as dry binder for immediate release. Dry granulation impacted tablet tensile properties, but did not significantly impact release performance. Lactoferrin-excipient compatibility was demonstrated for up to 2 years in ambient laboratory conditions. <b>Conclusions:</b> The study demonstrates that robust tablets can be produced using excipients and processes amenable to scale-up for industrial production. Consistent, stable, and suitably performing tablets were successfully produced using a variety of excipients, processing approaches, and across a broad concentration range with this cohesive biomacromolecule active pharmaceutical ingredient (API). Both immediate- and controlled release performance modes were possible.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176733","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":"Microfluidic Assembly of Poly(glutamic acid) Nanogels Through SPAAC Click Chemistry.","authors":"Pasquale Mastella, Stefano Luin","doi":"10.3390/pharmaceutics17091150","DOIUrl":"10.3390/pharmaceutics17091150","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Nanogels (NGs) are promising carriers for drug delivery due to their tunable size, biocompatibility, and capability to encapsulate sensitive molecules. However, conventional batch synthesis often lacks control over key parameters, such as size distribution and encapsulation efficiency. This study aimed to develop a microfluidic platform for the reproducible synthesis of poly(α-glutamic acid) (PGA)-based NGs using strain-promoted azide-alkyne cycloaddition (SPAAC) click chemistry and to investigate the effects of flow parameters on the physicochemical properties of nanogels. <b>Methods:</b> Functionalized PGAs (with azide and DBCO) were co-injected into a microfluidic system within a flux of acetone to form NGs via SPAAC. Flow rate ratios (FRR) and total flow rates were systematically screened at 25 °C, with tests at 50 °C. We evaluated the particle size, polydispersity index (PDI), zeta potential, and encapsulation efficiency (EE%) of doxorubicin-loaded NGs. <b>Results:</b> NGs with tunable sizes ranging from ~50 nm to >170 nm and low PDI (<0.1 in optimal conditions) were obtained. Higher FRR and total flow rates yielded smaller and more uniform NGs. Doxorubicin loading did not affect the nanogel size and uniformity, and in some cases, it improved them. The EE% reached up to ~65%, and ~40% for the best formulations. Elevated temperature improved the characteristics of drug-loaded nanogels at intermediate solvent ratios. Compared to batch synthesis, the microfluidic process offers enhanced reproducibility and size control. <b>Conclusions:</b> Microfluidic SPAAC synthesis enables precise and scalable fabrication of PGA NGs with controllable size and drug loading. This platform supports future integration of on-chip purification and monitoring for clinical nanomedicine applications.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177557","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":"An In Vitro-In Vivo Comparison of Two Levodopa Dry Powder Products for Inhalation: A Randomized Trial Comparing Inbrija and Levodopa Cyclops.","authors":"Julia M E Berends, Ettina J Wimmenhove, Marcel Hoppentocht, Paul Hagedoorn, Henderik W Frijlink, Floris Grasmeijer","doi":"10.3390/pharmaceutics17091149","DOIUrl":"10.3390/pharmaceutics17091149","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The pulmonary administration of levodopa enables a rapid absorption and onset of action, making it a suitable administration route for managing OFF episodes in Parkinson's disease. Currently, one dry powder product for inhalation (Inbrija) is available on the market, while another (Levodopa Cyclops) is in development. These two products differ substantially in terms of inhaler design, their use and resistance, and their powder formulations. This study aimed to investigate whether these differences translate into in vitro differences in aerosol characteristics and dissolution kinetics and whether any differences were also reflected in the in vivo performance. <b>Methods</b>: The in vitro aerosol characteristics were determined via Next Generation Impactor experiments, and the dissolution kinetics were determined with a modified paddle apparatus. A randomized crossover comparative bioavailability study with fasted healthy volunteers was conducted with Inbrija 84 mg and Levodopa Cyclops 45 mg, 90 mg, and 135 mg. <b>Results</b>: The results showed similar aerosol characteristics, but Levodopa Cyclops showed substantially faster dissolution behavior than Inbrija. Despite this in vitro difference, the pharmacokinetic profiles of Inbrija 84 mg and Levodopa Cyclops 90 mg were similar, with no differences in C_max, T_max, and AUC, showing bioequivalence between the two products. <b>Conclusions</b>: This suggests that the systemic absorption of levodopa via the lungs is not limited by dissolution but most likely by its permeation rate. This finding underscores the need to critically apply in vitro tests and critically interpret the results for predicting the in vivo performance of inhaled products.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177423","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":"A Modified Triaxial Electrospinning for a High Drug Encapsulation Efficiency of Curcumin in Ethylcellulose.","authors":"Xingjian Yang, Qiling Wang, Zhirun Zhu, Yi Lu, Hui Liu, Deng-Guang Yu, Sim-Wan Annie Bligh","doi":"10.3390/pharmaceutics17091152","DOIUrl":"10.3390/pharmaceutics17091152","url":null,"abstract":"<p><p><b>Background:</b> Although electrohydrodynamic atomization (EHDA) consistently provides drug-encapsulation efficiencies (DEE) far above those of conventional bottom-up nanotechnologies, the question of how to systematically push that efficiency even higher remains largely unexplored. <b>Methods:</b> This study introduces a modified triaxial electrospinning protocol tailored to the application and benchmarks it against two conventional techniques: single-fluid blending and coaxial electrospinning. Ethylcellulose (EC) served as the polymeric matrix, while curcumin (Cur) was chosen as the model drug. In the triaxial setup, an electrospinnable, drug-free EC solution was introduced as an intermediate sheath to act as a molecular barrier, preventing Cur diffusion from the core fluid. Ethanol alone was used as the outermost fluid to guarantee a stable and continuous jet. <b>Results</b>: This strategy provided a DEE value of 98.74 ± 6.45%, significantly higher than the 93.74 ± 5.39% achieved by coaxial electrospinning and the 88.63 ± 7.36% obtained with simple blending. Sustained-release testing revealed the same rank order: triaxial fibers released Cur the most slowly and exhibited the smallest initial burst release effect, followed by coaxial and then blended fibers. Mechanistic models for both fiber production and drug release are proposed to clarify how the tri-layer core-shell structure translates into superior performance. <b>Conclusions</b>: The modified triaxial electrospinning was able to open a new practical route to produce core-sheath nanofibers. These nanofibers could provide a higher DEE and a better sustained drug release profile than those from the coaxial and blending processes.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177364","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 Characterization of Citalopram-Loaded Thermosensitive Polymeric Micelles for Nasal Administration.","authors":"Fatima Rajab, Bence Sipos, Gábor Katona, Ildikó Csóka","doi":"10.3390/pharmaceutics17091147","DOIUrl":"10.3390/pharmaceutics17091147","url":null,"abstract":"<p><p><b>Background/Objectives:</b> The intranasal (IN) route of administration is a promising non-invasive approach for brain targeting, bypassing the blood-brain barrier and enhancing bioavailability. Citalopram hydrobromide (CT), a widely prescribed sparingly water-soluble selective serotonin reuptake inhibitor (SSRI), faces challenges with oral and intravenous administration, including delayed onset, adverse effects, and patient compliance issues. <b>Methods:</b> This study aimed to develop a novel thermoresponsive polymeric micelle (PM) system based on Pluronic^® copolymers (Pluronic F127 and Poloxamer 188) improving CT's solubility, stability, and nasal permeability for enhanced antidepressant efficacy. A preliminary study was conducted to select the optimized formulation. The preparation process involved using the thin-film hydration method, followed by freeze-drying. Comprehensive evaluations of optimized formulation characteristics included Z-average, polydispersity index (PdI), thermal behavior (lower critical solution temperature, LCST), encapsulation efficiency, X-ray powder diffraction (XRPD), thermodynamic solubility, and biological stability. Additionally, in vitro CT release and CT permeability in nasal conditions were studied. Stability under storage was also evaluated. <b>Results:</b> The optimized CT-PM formulation showed nanoscale micelle size (Z-average of 31.41 ± 0.99 nm), narrow size distribution (polydispersity index = 0.241), and a suitable thermal behavior for intranasal delivery (lower critical solution temperature (LCST) ~31 °C). Encapsulation efficiency reached approximately 90%, with an amorphous structure confirmed via XRPD, leading to a 95-fold increase in CT solubility. The formulation demonstrated appropriate biological and physical stability. In vitro studies showed a 25-fold faster CT release from optimized formulation compared to the initial CT, while CT-PM permeability in nasal conditions increased four-fold. <b>Conclusions:</b> This novel nanoscale thermosensitive formulation is a value-added strategy for nasal drug delivery systems, offering enhanced drug solubility, rapid drug release, stability, and improved permeability. This smart nanosystem represents a promising platform to overcome the limitations of conventional CT administration, improving therapeutic outcomes and patient compliance in depression management.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177275","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}