AAPS PharmSciTech最新文献

{"title":"Comprehensive Stability Assessment of Squalene in a Nanoemulsion Adjuvant and the SpiN-Tec Vaccine: HPLC Quantification, Stress Testing, and Stability Studies","authors":"Isabela Pereira Gomes,&nbsp;Graziella Gomes Rivelli,&nbsp;Flávia Fonseca Bagno,&nbsp;Natália Satchiko Hojo-Souza,&nbsp;Ana Luiza Chaves Maia,&nbsp;Liliane Martins dos Santos,&nbsp;Bruna Rodrigues Dias Assis,&nbsp;Natália Salazar de Castro,&nbsp;Wellington Miranda Vargas,&nbsp;Rafael Rodrigues de Barros,&nbsp;Natália Andrade de Freitas,&nbsp;Gisele Assis Castro Goulart,&nbsp;Renan Pedra de Souza,&nbsp;Santuza Maria Ribeiro Teixeira,&nbsp;Ana Paula Fernandes,&nbsp;Ricardo Tostes Gazzinelli,&nbsp;Eduardo Burgarelli Lages","doi":"10.1208/s12249-026-03542-z","DOIUrl":"10.1208/s12249-026-03542-z","url":null,"abstract":"<div><p>Squalene-based nanoemulsions are widely used as adjuvants in vaccine formulations, but their stability can be affected by environmental factors such as pH, oxidative stress, temperature, and light. We have produced a squalene nanoemulsion (CTVad1) to support the clinical development of new vaccines. This study aimed to develop and validate an HPLC method for squalene quantification in SpiN-Tec, a recombinant protein vaccine against COVID-19. We also aimed to evaluate the stability of the CTVad1 adjuvant and SpiN-Tec under controlled storage conditions. A reversed-phase HPLC method was developed and validated, and comprehensive forced degradation studies were performed on the raw material and SpiN-Tec under acidic, basic, oxidative, thermal, and photolytic conditions to demonstrate the stability-indicating capability of the method. Physicochemical, morphological, and biological characteristics were assessed, and stability studies of both the vaccine and the CTVad1 adjuvant were performed under accelerated and long-term conditions. The HPLC method was selective, precise, accurate, linear, and robust. Squalene raw material degraded under all tested conditions, whereas formulation in nano-sized globules improved its stability, with degradation observed only under hydrogen peroxide and light exposure. CTVad1 remained stable over time, exhibiting only minor, non-critical changes within the specification limits in both accelerated and long-term stability studies, regardless of the glass packaging used (clear or amber). In addition, the SpiN-Tec vaccine maintained its physicochemical and biological integrity under all tested conditions, with all evaluated parameters remaining within the established specification ranges. Our findings demonstrate that proper formulation, packaging, and storage conditions can preserve squalene stability in nanoemulsion-based vaccines, ensuring the quality, safety, and efficacy of the SpiN-Tec vaccine and its adjuvant throughout shelf life.</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":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03542-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148986549","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":"Nanovesicular Spanlastics Thermosensitive Gel for the Ocular Delivery of Voriconazole: Development, Ex Vivo Transcorneal Permeability, and In Vivo Evaluation in a Rabbit Model of Fungal Keratitis","authors":"Ghareb M. Soliman,&nbsp;Ayman Salama,&nbsp;Mona Qushawy,&nbsp;Mona F. Arafa,&nbsp;Nehal Elsherbiny,&nbsp;Helal F. Hetta,&nbsp;Mohamed M. Badran,&nbsp;Wael M. Elsaed,&nbsp;Yasmin N. Ramadan","doi":"10.1208/s12249-026-03511-6","DOIUrl":"10.1208/s12249-026-03511-6","url":null,"abstract":"<div><p>Fungal keratitis remains a leading cause of corneal blindness and eye loss worldwide. Conventional antifungal preparations such as those of voriconazole (VCZ) are often limited by rapid precorneal drug loss and poor corneal penetration, leading to suboptimal therapeutic outcomes. This study aimed to address these limitations and improve VCZ antifungal efficacy by incorporating it into nanovesicular spanlastics embedded within a thermosensitive Pluronic F127 gel. VCZ-loaded spanlastics were optimized using a multilevel categoric design and evaluated for VCZ entrapment efficiency (EE%), vesicle size (VS), polydispersity index (PDI), and zeta potential (ZP). The optimized formulation was embedded in Pluronic F127 gel, which was evaluated for gelation temperature, rheological properties, drug release, <i>in vitro</i> antifungal efficacy, <i>ex vivo</i> transcorneal permeability, and <i>in vivo</i> efficacy in a rabbit fungal keratitis (FK) model. The optimized formulation exhibited EE% of 95.91 ± 0.03%, VS of 91.32 ± 0.60 nm, PDI of 0.33 ± 0.03, and ZP of -34.90 ± 1.76 mV. VCZ spanlastics gel exhibited suitable gelation temperature, pH value, and spreadability. It also sustained VCZ release, improved its antifungal efficacy against<i> A</i>. <i>flavus</i>, and showed approximately five-fold higher transcorneal permeability compared with VCZ suspension. <i>In vivo</i>, the VCZ spanlastics gel demonstrated marked resolution of conjunctival redness absence of periocular discharge, and lower levels of the inflammatory marker CD8 compared with the VCZ suspension. These findings confirm the ability of VCZ spanlastics gel to overcome its limitations and highlight its promising potential as an effective topical ocular delivery system for the management of fungal keratitis.</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":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966020","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":"Smart Surface-Engineered Mesoporous Silica Nanoparticles for Brain Tumor Therapy: Overcoming the Blood–Brain Barrier for Advanced Theranostics","authors":"Rachana SP,&nbsp;Rahul Pokale,&nbsp;Deepanjan Datta,&nbsp;Gaurisha alias Resha Ramnath Naik,&nbsp;Sandesh Ramchandra Jadhav,&nbsp;Ritu Kudarha,&nbsp;Srinivas Mutalik,&nbsp;Namdev Dhas","doi":"10.1208/s12249-026-03522-3","DOIUrl":"10.1208/s12249-026-03522-3","url":null,"abstract":"<div><p>Brain tumors, particularly glioblastoma multiforme (GBM), remain among the most lethal forms of cancer due to their aggressive nature and the formidable challenge posed by the blood–brain barrier (BBB), which restricts the delivery of therapeutic agents. Conventional treatment modalities, including surgery, radiotherapy, and chemotherapy, often fail to achieve effective and targeted therapy without inducing systemic toxicity or damaging healthy brain tissue. In recent years, mesoporous silica nanoparticles (MSNs)have emerged as a versatile platform for targeted brain tumor therapy because of their high surface area, tunable pore structure, biocompatibility, and ease of surface functionalization. This review critically examines advanced surface functionalization strategies, including chemical functionalization (amine, thiol, carboxyl groups), ligand conjugation (antibodies, aptamers, peptides), and polymeric coatings (PEG, chitosan, PLGA) that enhance BBB penetration, facilitate tumor-specific targeting, and enable stimuli-responsive drug release (different types of exogenous and endogenous). We also explore the interactions of these modifications with key signaling pathways (e.g., Wnt/β-catenin, PDGF-B, TGF-β) that regulate BBB integrity and glioma progression. Special emphasis is placed on how surface-engineered MSNs can improve site-specific drug delivery, increase therapeutic accumulation in brain tumor tissue, and minimize off-target toxicity. Despite the considerable promise demonstrated by these techniques in preclinical glioma models, obstacles such as scalable synthesis, regulatory compliance, and long-term biosafety must be addressed to facilitate clinical translation. This review focuses specifically on brain tumor targeting via functionalized MSNs and provides mechanistic insights while highlighting emerging strategies to advance MSNs as next-generation therapeutics for brain tumor treatment.</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":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03522-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966044","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":"Rutin loaded nanosponges for treatment of peptic ulcer: in silico, pharmacodynamic and pharmacokinetic studies","authors":"Monica RP Rao,&nbsp;Bushra Ashpak Bagwan","doi":"10.1208/s12249-026-03506-3","DOIUrl":"10.1208/s12249-026-03506-3","url":null,"abstract":"<div><p>Peptic ulcer disease (PUD) is a multifactorial condition influenced by oxidative stress, <i>Helicobacter pylori</i> infection and excessive gastric acid secretion. Rutin (RTN), a plant-derived flavonoid with antioxidant, anti-inflammatory and proton pump inhibition properties, offers therapeutic promise but suffers from poor aqueous solubility and low bioavailability. To overcome these limitations, RTN-loaded β-cyclodextrin-based nanosponges (RTN-NS₄) were developed and extensively characterized. Phase solubility studies revealed A_L type of curve. DSC and PXRD indicated enhanced amorphization while FTIR confirmed successful drug encapsulation. SEM imaging revealed flaky, nanoscale morphology. RTN-NS₄ exhibited a 25.4-fold increase in saturation solubility compared to RTN. Antioxidant potential, assessed by DPPH assay, showed significantly higher antioxidant activity for RTN-NS₄ of 87.91% at 500 μg/ml, indicating enhanced ROS-scavenging ability. Molecular docking studies further confirmed RTN’s strong binding affinity towards H⁺/K⁺-ATPase (glide energy of –62.822 kcal/mol) showing enhanced binding affinity and complex stability. In comparison, vonoprazon showed glide energy of –58.450 kcal/mol. These studies also confirmed that RTN has greater binding with NS (glide energy:–37.924 kcal/mol) than β-CD (glide energy:–33.034 kcal/mol). RTN-NS₄ achieved 42 ± 7.23% ulcer inhibition in ethanol-induced gastric ulcers in Wistar rats, surpassing RTN (22.17 ± 6.53%) but 18% lower than omeprazole (60.16 ± 8.23%). Histological studies confirmed moderate mucosal protection and reduced inflammation in RTN-NS₄-treated rats. These results underscore RTN-NS₄ as promising nanophyto-therapeutic system offering synergistic antioxidant, anti-inflammatory and PPI activity effects for effective ulcer management without the concomitant side effects of PPIs.\u0000</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":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966112","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":"Degree of Carboxymethyl Substitution on Tara Gum Influences the Mucoadhesive and Physicochemical Performance of Gastroretentive Tablets","authors":"Anand Swaroop Gupta,&nbsp;Bipul Chandra Karmakar,&nbsp;Kaushik Mukherjee,&nbsp;Amalesh Samanta,&nbsp;Asish Kumar Mukhopadhyay,&nbsp;Tapan Kumar Giri","doi":"10.1208/s12249-026-03536-x","DOIUrl":"10.1208/s12249-026-03536-x","url":null,"abstract":"<div><p>The present study investigates the effect of the degree of carboxymethyl substitution in tara gum (TG) on the physicochemical and mucoadhesive properties of gastroretentive tablets. The synthesis of carboxymethyl TG (CMTG) was optimized under various reaction conditions with respect to degree of substitution (DS). The DS varied from 0.47 ± 0.002 to 1.14 ± 0.014 depending on the reaction conditions. The DS significantly influenced the flow properties, swelling behavior, and erosion of the tablets. <i>Ex vivo</i> mucoadhesion studies on goat stomach mucosa revealed that both mucoadhesive strength (MS) and mucoadhesive time (MT) varied with changes in DS. MS and MT progressively increased from 45.51 × 10³ ± 2.979 to 111.18 × 10³ ± 3.901 dynes/cm² and from 272.66 ± 2.561 to 517.33 ± 2.516 min, respectively, with increasing DS from 0.47 ± 0.002 to 1.05 ± 0.046, owing to enhanced hydrogen bonding between the -COOH groups of CMTG and functional groups of mucin. However, a further increase in DS to 1.14 ± 0.014 decreased MS and MT to 101.75 × 10³ ± 0.297 dynes/cm² and 504.33 ± 1.041 min, respectively, primarily due to excessive protonation in acidic media, which increased the rigidity of the polymeric networks and reduced interactions between polymeric chains and mucin. The most notable finding of this study was that the MS and MT values of the optimized carboxymethylated derivative (CMTG-4) were superior to those of the commercial mucoadhesives CMC, Carbopol 934, and pectin.</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":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148927406","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":"Enhancing Curcumin Performance via PVP K30 Solid Dispersion: Synergistic Potential in Combination with Conventional Chemotherapeutic Agents in NSCLC Cells","authors":"Daniel Hernandez-Patlan,&nbsp;Elvia A. Morales Hipólito,&nbsp;Carla O. Contreras-Ochoa,&nbsp;Marisol Mir-Garcia,&nbsp;Hugo Cortés Martínez,&nbsp;Adriana Tejeda-Cruz,&nbsp;Sandra L. Hernández-Ojeda,&nbsp;Javier J. Espinosa-Aguirre,&nbsp;Raquel López-Arellano","doi":"10.1208/s12249-026-03534-z","DOIUrl":"10.1208/s12249-026-03534-z","url":null,"abstract":"<div><p>Curcumin (CUR) has shown promising anticancer activity against non-small cell lung cancer (NSCLC), but its poor biopharmaceutical properties limit its applications. This study aimed to optimize a solid dispersion of CUR with polyvinylpyrrolidone K30 (PVP K30) to enhance its biopharmaceutical properties and to evaluate its ability to enhance cytotoxic activity of conventional chemotherapeutic drugs (Afatinib, Cisplatin, and Metformin) in A549 NSCLC cells. Solid dispersions (CUR:PVP K30 at ratios of 1:9, 1:12, and 1:15) were prepared using four different protocols. The 1:9 solid dispersion obtained with Protocol 4 exhibited the highest thermodynamic solubility (&gt; 14,000-fold increase; 408.00 µg/mL) and an improved intrinsic dissolution rate. Furthermore, the characterization of the solid dispersions by DSC, FTIR and PXRD confirmed the formation of amorphous solid dispersions, which are suggested to be stable according to the thermal stress study at 70°C. Cytotoxicity was assessed via MTS assay after 48 h. The Half-maximal inhibitory concentration (IC₅₀) values were 0.03, 0.04, 3.30 and 0.13 mg/mL for Afatinib, Cisplatin, Metformin and CUR:PVP K30 (1:9, protocol 4), respectively. The combination of conventional chemotherapeutic drugs with the 1:9 CUR:PVP K30 formulation at Minimum effective concentration (MEC) or IC₅₀ significantly enhanced cytotoxicity. Analysis of the combination index (CI) revealed synergistic interactions, as values less than 1 (CI &lt; 1) were obtained for all combinations. These findings demonstrate that the use of solid dispersions significantly improves the solubility of CUR, potentially offering a promising strategy for enhancing the <i>in vitro</i> cytotoxic activity of conventional chemotherapeutic agents.</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":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03534-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148927407","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":"Optimization of Curcumin-Ascorbic Acid Cocrystal for Enhanced Solubility, Tablettability, and Oral Bioavailability: Structural, Functional, and Pharmacokinetic Insights","authors":"Jidnyasa Pantwalawalkar,&nbsp;Namdeo Jadhav,&nbsp;Sopan Nangare","doi":"10.1208/s12249-026-03540-1","DOIUrl":"10.1208/s12249-026-03540-1","url":null,"abstract":"<div><p>Curcumin (CUR) exhibits broad therapeutic potential across multiple disease conditions. However, it’s extremely low aqueous solubility, poor dissolution, and limited oral bioavailability constrain its clinical utility. Therefore, the present study aimed to address the aforesaid limitations through design, optimization, and evaluation of a pharmaceutical cocrystal of CUR with ascorbic acid (CUR-AA-C). Initially, <i>in silico</i> modelling was employed to predict drug-coformer interactions, followed by optimization of the CUR-AA stoichiometry using a solvent-evaporation technique. The resulting solid form was systematically characterized by spectral techniques to confirm cocrystal formation. Subsequent evaluations included solubility assessment, antioxidant activity testing, and tablettability studies. A Design of Experiments (DoE) approach was further utilized to optimize the tablet formulation, and the pharmacokinetic performance of the optimized cocrystal tablet was assessed through <i>in vivo</i> bioavailability studies. Spectroscopic techniques confirmed successful CUR-AA-C formation. It exhibited a significant enhancement in solubility (12-fold in SGF and 13-fold in SIF) compared to neat CUR, attributed to modifications in the crystal lattice structure induced by the coformer. Antioxidant assays demonstrated a two-fold improvement in activity. Tablettability evaluations revealed an increase in compressibility and mechanical strength, supporting the development of robust tablets. Furthermore, the DoE-optimized cocrystal tablet showed a 6.3-fold increase in oral bioavailability relative to unmodified CUR. Overall, the prepared cocrystal demonstrated potential to enhance solubility, dissolution, manufacturability, and bioavailability, thereby improving the clinical applicability of poorly soluble natural compounds.</p></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148927509","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":"Retraction Note: Agranulocytosis-Protective Olanzapine-Loaded Nanostructured Lipid Carriers Engineered for CNS Delivery: Optimization and Hematological Toxicity Studies","authors":"Dnyandev G. Gadhave,&nbsp;Amol A. Tagalpallewar,&nbsp;Chandrakant R. Kokare","doi":"10.1208/s12249-026-03543-y","DOIUrl":"10.1208/s12249-026-03543-y","url":null,"abstract":"","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148927337","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":"Design of Eudragit E100 Films Incorporating Lipoic Acid as a Permeability-Enhancing Platform for Prednisolone Delivery in the Treatment of Ophthalmic Diseases","authors":"Karina Bierbrauer,&nbsp;Laura Comini,&nbsp;Marcos Cometto,&nbsp;Aldana Ceballos,&nbsp;Leandro Nieto,&nbsp;Vanina Alamino,&nbsp;Gabriela Castelli,&nbsp;Silvia Farfán,&nbsp;Victoria Leonhard,&nbsp;Dante Beltramo,&nbsp;Roxana Alasino","doi":"10.1208/s12249-026-03517-0","DOIUrl":"10.1208/s12249-026-03517-0","url":null,"abstract":"<div><p>Prednisolone (PRED), a widely used corticosteroid for the treatment of ocular inflammation, has limited bioavailability due to its poor water solubility. In this study, Eudragit E100-based films incorporating polyethylene glycol 400 (PEG) and α-lipoic acid (ALA) as plasticizers were developed and characterized to improve the ocular delivery and corneal permeability of PRED. ALA, which is also known for its antioxidant and therapeutic properties in ocular surface disorders, plays a dual role by enhancing both the mechanical properties and drug delivery performance of the films. The E100:PEG:ALA:PRED (1:0.3:0.2:0.2) formulation exhibited flexibility, mucoadhesion, and controlled-release behavior. Furthermore, cell viability and wound-healing assays were performed to evaluate the biocompatibility of the films. In addition, <i>ex vivo</i> permeability studies using porcine corneas revealed significantly enhanced PRED penetration compared with a commercial eye drop formulation (Sophipren Ofteno® 1%) and demonstrated that the films induced minimal corneal irritation. Based on these findings, Eudragit E100 films containing ALA, PEG, and PRED may represent a promising alternative to conventional ophthalmic suspensions, as they provide sustained drug release while potentially simplifying dosing regimens.</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":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148927256","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":"Thermogelling Hydrogel for Sustained Topical Delivery of Quercetin for the Treatment of Atopic Dermatitis","authors":"Saiswari Dwibedi,&nbsp;Ganesh Kumar,&nbsp;Sree Prakash Pandey,&nbsp;Nishi Agrawal,&nbsp;Shweta Yadav,&nbsp;Nishat Parveen Siddiqui,&nbsp;Manoj Kumar,&nbsp;Ravi Shankar Pandey","doi":"10.1208/s12249-026-03525-0","DOIUrl":"10.1208/s12249-026-03525-0","url":null,"abstract":"<div><p>Atopic dermatitis is a chronic inflammatory skin disease clinically characterized by pruritus, dryness, and eczematous lesions, resulting from a combination of environmental, immunological, and genetic factors. In this study, the quercetin-loaded thermosensitive hydrogel (QU-THG) was developed using the cold method and optimized through a Box-Behnken design. The concentrations of Pluronic F-127 and DMSO, and stirring speed were selected as independent variables, and sol–gel transition temperature, gelation time, and viscosity were evaluated as responses. The optimized formulation contained 18% w/v Pluronic F-127, showed a gelation temperature of 3 ± 0.3 °C, a gelation time of 5.3 ± 0.8 min, and a viscosity of 78 ± 5.3 cPs. The hydrogel underwent a reversible sol–gel transition, forming <i>in situ</i> stable gel at physiological temperature and enhances skin residence time. <i>In vitro</i> release studies demonstrated 49.9 ± 5.23% quercetin release within 7 h and 92.5 ± 3.1% over 24 h, following a non-Fickian diffusion mechanism based on the Korsmeyer–Peppas model, indicating the combined influence of diffusion and polymer relaxation. Skin permeation studies revealed maximum permeation at 18% w/v Pluronic F-127, likely due to reduced micellar packing and improved thermodynamic activity of quercetin. <i>In vivo</i> studies confirmed a significant reduction in inflammation and accelerated skin recovery compared to the negative control. Clinical scoring further confirmed a highly significant difference (<i>p &lt; </i>0.0001) using one-way ANOVA followed by Tukey’s post hoc test. The optimized QU-THG demonstrated controlled gelation, desirable rheological properties, and sustained drug release, resulting in improved therapeutic outcomes, thereby supporting its applicability as an effective topical system for atopic dermatitis 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":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148927858","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}