AAPS PharmSciTech最新文献

{"title":"Vilazodone Hydrochloride-Loaded Nanostructured Lipid Carrier In Situ Gel for Intranasal Nose-to-Brain Antidepressant Delivery","authors":"Khushi Shah,&nbsp;Rajeshkumar S. Palva,&nbsp;Mitali Patel,&nbsp;Musaratafrin Saiyed,&nbsp;Nisha Singh,&nbsp;Hardik Zala,&nbsp;Rajnikant M. Suthar,&nbsp;Krunal Detholia","doi":"10.1208/s12249-026-03566-5","DOIUrl":"10.1208/s12249-026-03566-5","url":null,"abstract":"<p>The Oral delivery of vilazodone hydrochloride (VLZ), a serotonin partial agonist–reuptake inhibitor for major depressive disorder, suffers from extensive hepatic first-pass metabolism, food-dependent absorption, and poor blood–brain barrier (BBB) penetration, limiting its central therapeutic impact. Here, VLZ-loaded nanostructured lipid carriers (NLCs) were engineered and embedded within a Poloxamer 407/188–chitosan thermosensitive <i>in situ</i> gel to enable direct nose-to-brain delivery. The NLCs were fabricated by combined high-shear and high-pressure homogenisation and optimised through central composite design, yielding a batch with particle size 24.74 ± 2.23 nm, polydispersity index 0.248 ± 0.012, and entrapment efficiency 91.37 ± 4.56%. The lyophilised NLCs were incorporated into an <i>in situ</i> gel with a physiologically appropriate gelation temperature of 34°C and gelation time of 42 s. Fourier Transform Infrared FTIR spectroscopy confirmed complete drug encapsulation, evidenced by disappearance of the diagnostic nitrile (C≡N) absorption band, while DSC and XRPD verified conversion of VLZ to an amorphous state within the lipid matrix. Drug release followed Korsmeyer–Peppas kinetics, sustained over 24 h, and the formulation remained stable under refrigerated storage. In Swiss albino mice, the intranasal NLC-<i>in situ</i> gel (1 mg/kg) produced a profound antidepressant-like effect relative to oral pure drug (10 mg/kg) across open field, tail suspension, and sucrose preference tests, consistent with enhanced nose-to-brain delivery via the olfactory and trigeminal pathways. Hence this nanocarrier–hydrogel strategy offers a promising, non-invasive route to enhanced CNS delivery of antidepressants.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 8","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149189957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an Injectable Boronic Ester Nanocomposite Hydrogel for pH- and Thermo-Responsive Gentamicin Delivery and Antibacterial Activity","authors":"Mahmoud H. Othman","doi":"10.1208/s12249-026-03559-4","DOIUrl":"10.1208/s12249-026-03559-4","url":null,"abstract":"<div><p>Infected wounds require localized antimicrobial treatment strategies that provide sustained drug release, reduce systemic antibiotic exposure, and promote tissue repair. This study reports an infection-responsive <b>nanocomposite hydrogel</b> platform based on dynamic covalent boronic ester chemistry for triggered topical antibiotic delivery. Phenylboronic acid (PBA)-functionalized cationic nanoparticles (PBA-NPs) were employed as three-dimensional crosslinkers and combined with poly(vinyl alcohol) (PVA) to construct an injectable <b>nanocomposite hydrogel</b> via reversible boronic ester interactions. The <b>nanocomposite hydrogel</b> was characterized for morphology, injectability, rheological properties, stimuli-responsive behavior, <i>in vitro</i> antibiotic release, and antibacterial activity against <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa.</i> The resulting <b>nanocomposite hydrogel</b> exhibited a gel–sol transition at 39.7°C, while the pH-dependent chemistry of the boronic ester network supports enhanced network dissociation under mildly acidic conditions (pH 6.5). This dual pH- and thermo-responsive behavior enabled on-demand release of encapsulated gentamicin sulfate while preserving viscoelastic recovery consistent with dynamic network reconstruction. The cationic PBA-NPs exhibited intrinsic antibacterial activity and generated enhanced antimicrobial effects when combined with gentamicin. Zones of inhibition reached 22 mm (<i>S. aureus</i>) and 25 mm (<i>P. aeruginosa</i>) at 3% drug loading. Collectively, these findings demonstrate that dynamic covalent boronic ester <b>nanocomposite hydrogel</b> represents a promising injectable platform for infection-responsive localized antibiotic delivery and antibacterial wound management.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149189912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymer-based Vaginal Insert Systems: Engineering Controlled Drug Delivery for Women’s Health","authors":"Shruti Kadam,&nbsp;Mansvi Dabhoya,&nbsp;Riya Patel,&nbsp;Shreeraj Shah","doi":"10.1208/s12249-026-03560-x","DOIUrl":"10.1208/s12249-026-03560-x","url":null,"abstract":"<div><p>Polymer-based vaginal inserts have emerged as a promising approach for localized and systemic drug delivery, demonstrating improved therapeutic efficacy, prolonged drug residence, controlled release and enhanced patient compliance compared to conventional vaginal dosage forms. This article gives a complete overview of the design and development of polymer-based vaginal inserts, covering the influence of vaginal physiology, mucoadhesion and polymer selection on formulation performance. The properties and applications of natural, synthetic, and hybrid polymers, and current breakthroughs in fabrication technologies such as freeze-drying, solvent casting, hot-melt extrusion, electrospinning, and 3D printing are covered. Also examined are several drug release techniques such as sustained, swelling-controlled, stimuli-responsive and mucoadhesive systems. Moreover, the therapeutic potential of vaginal inserts for the treatment of vulvovaginal infections, endometriosis, cervical cancer, uterine fibroids, menopause-related illnesses, contraception and HIV prevention is emphasized. Finally, the future directions of emerging technologies, such as nanotechnology, smart polymers, artificial intelligence, and personalized drug delivery systems, are discussed for the clinical translation and enhanced efficacy of polymer-based vaginal drug delivery systems for women’s reproductive health.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149189910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody-Drug Conjugate Manufacturing: Facility Design, Process Safety, and Regulatory Considerations","authors":"Ashley Harp","doi":"10.1208/s12249-026-03502-7","DOIUrl":"10.1208/s12249-026-03502-7","url":null,"abstract":"<div><p>This paper presents an in-depth examination of the manufacturing, formulation, and fill/finish processes for traditional antibody–drug conjugates (ADCs), with particular emphasis on cytotoxic ADCs and the unique risks associated with their production. ADCs inherent toxicity demands rigorous facility and equipment design, proactive risk assessment, and robust risk mitigation strategies. We describe the multiple processes and facility types involved in producing ADCs, with a more detailed focus on drug product facilities. In addition, we study the critical facility risk areas encountered and effective strategies for managing and overcoming those risks. While it is well understood that containment is a critical risk area in the ADC modality, there has been a significant amount of work published with respect to specific containment strategies and solutions for unique unit operations and this area has only been summarized in this review. The paper also addresses regulatory compliance—highlighting EU GMP Annex 1 expectations—and underscores the importance of robust containment strategies and holistic design elements for preventing cross contamination, personnel exposure, and mitigating environmental impact.</p></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Polymeric Microneedles with Variable Lengths for Delivery of Ebselen in Sporotrichosis","authors":"Camila Patricio Rissi,&nbsp;Lorena Rafaella Salvador,&nbsp;Thalita Schilive Faccin,&nbsp;Ana Luiza de Paula Vasconcelos,&nbsp;Érika Seki Kioshima,&nbsp;Maria Sueli Felipe,&nbsp;Marcos Luciano Bruschi","doi":"10.1208/s12249-026-03565-6","DOIUrl":"10.1208/s12249-026-03565-6","url":null,"abstract":"<div><p>Sporotrichosis is a subcutaneous mycosis of public health relevance due to the increased zoonotic transmission associated with felines. Ebselen (EB), a poorly water-soluble organic selenium compound, reacts with thiol groups of redox proteins, increases oxidative stress, and causes fungal death. Microneedles (MN) create microchannels in the skin, disrupting the stratum corneum and allowing the release and diffusion of the drug into deeper layers, potentially reaching blood capillaries. Sporotrichosis is typically treated with intravenous or oral therapies. Thus, this study developed polymeric MN for EB delivery, improving drug incorporation and dispersion while providing a minimally invasive topical alternative. A spectrophotometric method for EB analysis was validated. The molds (long and short microneedles) proved to be transparent, flexible, and easy to remove from the MN. The best formulations (F02, F09, F16, and F17) were selected. EB solubility was 0.15%. In light microscopy and scanning electron microscopy (SEM), both MN types presented well-defined and intact structures. In the compression test, the best formulation (F17) was selected in both molds. <i>In vitro</i> evaluation of the EB release profile from F17 showed that the long mold formulation released the drug faster than the short mold one. <i>In vitro</i> analysis of antifungal activity showed that the formulation containing EB induced the formation of an inhibitory halo, demonstrating antifungal activity against the fungus <i>Sporothrix brasiliensis</i>. Thus, the current results suggest that the MN containing EB is a promising system. Additional biological studies are required to fully assess their safety and performance in the context of sporotrichosis.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03565-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stimuli-Responsive Hydrogel Systems for Breast Cancer Therapy: Advances in Targeted Delivery and Tumor Microenvironment Modulation","authors":"Pooja Dave,&nbsp;Kiran Dudhat","doi":"10.1208/s12249-026-03555-8","DOIUrl":"10.1208/s12249-026-03555-8","url":null,"abstract":"<div><p>Breast cancer (BC) stands as a major medical concern for women because treatment hurdles include drug resistance combined with treatment failure and severe side effects and the intricate tumor microenvironment (TME). The treatment-resistant breast cancer subtype triple-negative breast cancer (TNBC) exhibits high aggressiveness through its failure to respond to targeted treatment yet maintains substantial metastatic potential. Hydrogels that react to stimuli have recently shown promise as solutions for solving these clinical issues. These hydrogels show response to precise stimuli which include pH, temperature and light and magnetic fields and biological elements including glutathione together with overexpressed enzymes MMP2 and MMP9 that appear within BC tumors. Hydrogel systems that respond to enzymes release drugs precisely at tumors thus minimizing drug side effects and optimizing their therapeutic effects. Hydrogel systems become more effective because of their ability to control drug delivery and combine various treatments when nanomaterials are incorporated as parts of their structure. Hydrogels must have adequate mechanical toughness because it enables them to withstand physical pressure without losing their drug release capabilities throughout the extended treatment period. This review has demonstrated that hydrogel-based drug delivery systems decrease tumor dimensions while inhibiting metastasis making them an advanced treatment strategy for BC management. The novel hydrogel platforms will lead to individualized treatment methods which show substantial promise to enhance breast cancer therapy results.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Controlling Residual Protein Impurities in Active Pharmaceutical Ingredients (APIs) by Derivative Size-Exclusion High-Performance Liquid Chromatography (SEC-HPLC)","authors":"Andrew Ramirez,&nbsp;Funing Yan,&nbsp;Xiaole Shao,&nbsp;Ce Qin,&nbsp;Zeena Williams,&nbsp;Heewon Lee,&nbsp;Shanzhi Wang","doi":"10.1208/s12249-026-03539-8","DOIUrl":"10.1208/s12249-026-03539-8","url":null,"abstract":"<div><p>This study aimed to develop a reliable protein labeling strategy for detecting enzymes in chemically complex active pharmaceutical ingredient (API)-rich environments where dimethyl sulfoxide (DMSO) is commonly used as the solvent. We compared two lysine targeting fluorescent dyes and identified NHS-fluorescein as superior to fluorescein isothiocyanate (FITC), yielding stronger signals and consistent linearity between protein concentration and absorbance intensity. Optimization experiments revealed that higher protein and dye concentrations improved labeling efficiency, with 500 μM NHS-fluorescein providing reproducible signals. Importantly, labeling remained robust across varying conditions: DMSO enhanced performance at 20—25% but reduced efficiency at 50%, while detergent effects varied by type, with zwitterionic and non-ionic detergents supporting efficient labeling and ionic detergent nearly abolishing it. The optimized protocol proved applicable to real industrial enzyme (Protein X) and maintained quantitative measurability even in the presence of diverse small molecules. Notably, these experiments could be transferred easily from size exclusion chromatography (SEC)-HPLC to SEC-UPLC. Together, these results establish a versatile, sensitive, and broadly applicable approach for protein labeling and detection in chemically challenging environments, with strong potential for applications in pharmaceutical research, compound screening, protein quantification, and industrial quality control.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutamine-tagged Sorafenib and Atorvastatin Coloaded Polymeric Nanoparticles for Hybrid Cell Death Induction in Colorectal Cancer: Part I Formulation, Characterization, In-vitro/In-vivo Safety and Efficacy Evaluation","authors":"Vivek Yadav,&nbsp;Sayali Dighe,&nbsp;Pratik Dhake,&nbsp;Sanyog Jain","doi":"10.1208/s12249-026-03546-9","DOIUrl":"10.1208/s12249-026-03546-9","url":null,"abstract":"<div><p>The present study explores the potential of sorafenib (SOR) and atorvastatin (ATST) to induce a ferroptosis and apoptosis-based hybrid cell death mechanism. The synergistic ATST + SOR combination was delivered through Glutamine-tagged PLGA nanoparticles (ATST + SOR/G-PLGA NPs) to promote intratumoral specificity. The formulation was optimized using DesignExpert® software by adopting Box-Behnken design (BBD). The optimized ATST + SOR/G-PLGA NPs had a spherical particle size of ~ 178.3 ± 12.6 nm, a PDI of 0.151 ± 0.08, and a Z-potential of -24.8 ± 5.8 mV. The formulation revealed a biphasic sustained release with higher release at acidic pH. In-vitro biological assessment showed a dose-dependent decrease in cell viability with reduced IC₅₀ values. In the presence of ferrostatin-1, the IC₅₀ value was significantly increased. The exposure to ATST + SOR/G-PLGA NPs led to elevated levels of malondialdehyde (MDA), reactive oxygen species (ROS), glutathione (GSH), increased late apoptotic/necrotic cells, and mitochondrial membrane depolarization. Pharmacokinetic study revealed a 2.63- and 2.93-fold improved AUC_0-∞, and 2.58- and 2.84-fold improvement in MRT as compared to free SOR and ATST. Preclinical efficacy study showed a marked reduction in tumor volume and a higher inhibition rate. Toxicity assessment revealed no signs of systemic or organ toxicity, implying suitability of formulation for <i>in-vivo</i> delivery. In a nutshell, the proposed strategy offers a powerful avenue to manage advanced malignancies by inducing a hybrid cell death mechanism. Also, the nutrient transporter targeted polymeric nanosystems present an effective approach, which warrants further investigation.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Novel Strategies for Improving the Bioavailability of Docetaxel","authors":"Oly Katari,&nbsp;Siddhesh Warke,&nbsp;Sanyog Jain","doi":"10.1208/s12249-026-03562-9","DOIUrl":"10.1208/s12249-026-03562-9","url":null,"abstract":"<div><p>In today’s world, research has evolved a lot in the field of cancer and docetaxel (DTX) has been intensively studied for its ability to cure different types of cancers. However, the intravenous delivery of DTX puts forth various undesirable side effects, while oral delivery has its own solubility and permeability drawbacks. The advancements in research have focused on overcoming these disadvantages by developing novel and efficient DTX-based drug delivery systems. The review aims at identifying challenges faced by DTX and thereby forecasting the different DTX formulations established to surpass them. The successful DTX delivery is mediated by certain efficient nanocarriers, inclusion complexes, etc., effectively destroying the cancerous cells. The current clinical status of these formulations has also been listed in this review. The dedicated efforts of researchers have been fruitful in site-specific targeting of DTX by novel formulations, thus enhancing its antitumor effect. However, this success has been restricted only to preclinical studies and only a few formulations have entered the CTs, while none have received market approval. A deep understanding of the basics of nanoformulations, along with their toxicological insights and flexible production procedures, will help to combat the clinical hurdles faced by them.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal Delivery of a Thermosensitive Gel Co-loaded with Temozolomide and N-acetylcysteine: In Vitro and In Vivo Evaluation","authors":"Raghda abd el moneum Ali Abdel Mawla,&nbsp;Wedad Sakran,&nbsp;Fares Ibrahim Farag Masry,&nbsp;Mohammed Salah Ahmed Teiama","doi":"10.1208/s12249-026-03551-y","DOIUrl":"10.1208/s12249-026-03551-y","url":null,"abstract":"<div><p>This study was designed to develop and optimize a thermosensitive intranasal gel incorporating temozolomide (TMZ) and N-acetylcysteine (NAC) as a promising platform for direct nose-to-brain drug delivery. Formulations were fabricated via cold technique utilizing Carbopol 934P and poloxamer 407 to improve gelation and mucoadhesion. After evaluating the formulations for clarity, pH, gelation temperature, gelling time, mucoadhesion, and drug loading, the formula A13 was elected as the optimized formulation based on a factorial design optimization approach. The optimized formula was further evaluated for stability, <i>ex-vivo</i> permeability, histopathology and <i>in-vivo</i> pharmacokinetic in rats. Compared with the corresponding <i>in-situ</i> gels containing the pure drugs, formulation A13 enhanced the ex-vivo nasal mucosal permeation of TMZ and NAC by 1.42-fold and 1.64-fold, respectively, indicating the superior permeability-enhancing effect of A13. Furthermore, histopathological examination revealed no evidence of structural damage following administration of formulation A13, confirming its safety for intranasal application. The <i>in-vivo</i> studies performed on rats showed significantly higher Cmax and AUC _0–24 results in brain of the optimized A13 by 1.4, 1.4, 2.6 and 1.87 folds in TMZ and NAC, respectively compared to <i>in-situ</i> gel of pure TMZ and <i>in-situ</i> gel of pure NAC, with a delayed (Tmax). The brain-to-blood concentration ratios of the TMZ–NAC-loaded <i>in-situ</i> gel were consistently higher than those of the pure-drug <i>in-situ</i> gels at most sampling time points, indicating more efficient nose-to-brain transport. Overall, these findings demonstrate that the optimized A13 is a promising and safe intranasal delivery system for enhancing the nose-to-brain delivery and bioavailability of TMZ and NAC.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}