AAPS PharmSciTech最新文献

{"title":"Practical Pipetting Optimization Strategies for Accurate Concentration Measurement of High-Concentration Protein Formulations","authors":"Shang-Yin Wu,&nbsp;Yun-Jie He,&nbsp;Ci Qian,&nbsp;Si-Ru Zhong,&nbsp;Hong-Xing Xiao,&nbsp;Changyun Xiong,&nbsp;Bin Di,&nbsp;Wei-Jie Fang","doi":"10.1208/s12249-026-03553-w","DOIUrl":"10.1208/s12249-026-03553-w","url":null,"abstract":"<div><p>High-concentration protein formulations for subcutaneous administration have developed rapidly, while viscosity-related pipetting errors remain a key bottleneck for accurate protein concentration quantification, with commercial detection instruments showing significant limitations in direct measurement of these samples. Here, we developed two pipetting-optimized quantification strategies using two high-concentration monoclonal antibody formulations with distinct viscosities as models: a motorized continuous pipette-based direct measurement method and a weight-corrected method. We validated the high accuracy and repeatability of the motorized continuous pipette for high-viscosity liquid handling, and systematically compared the performance of our optimized methods with the traditional manual pipetting method and three mainstream commercial protein analyzers. Direct measurements using the three evaluated analyzers showed formulation-dependent deviations under the tested conditions. Both optimized workflows improved pipetting precision and provided concentration estimates with improved repeatability for the two high-concentration mAb formulations examined. These findings support motorized pipetting and weight correction as practical options when viscosity compromises volumetric transfer, while their applicability to other protein modalities and formulations with intermediate viscosity requires further validation.</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":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029367","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 Solid Lipid Nanoparticles Loaded with Carmustine and Temozolomide for Glioblastoma Treatment in Mice","authors":"Ayşe Ünal,&nbsp;Güliz Ak,&nbsp;Habibe Yılmaz,&nbsp;Tuğba Karakayalı Kavruk,&nbsp;Ayça Erek,&nbsp;Reşat Serhat Erbayraktar,&nbsp;Zübeyde Erbayraktar,&nbsp;Ayça Erşen Danyeli,&nbsp;Buket Özel,&nbsp;Nur Selvi Günel,&nbsp;Derya Erışık,&nbsp;Yiğit Uyanıkgil,&nbsp;Nuriye Nuray Ulusu,&nbsp;Duygu Aydemir,&nbsp;Hayal Boyacıoğlu,&nbsp;Şenay Şanlıer","doi":"10.1208/s12249-026-03496-2","DOIUrl":"10.1208/s12249-026-03496-2","url":null,"abstract":"<div><p>Glioblastoma multiforme remains one of the most aggressive and lethal central nervous system malignancies, primarily due to the restrictive nature of the blood–brain barrier which severely limits the efficacy of systemically administered chemotherapeutics. To address this critical challenge, this study aims to overcome the limitations of conventional glioblastoma treatment by developing solid lipid nanoparticles (SLNs) co-loaded with temozolomide and carmustine for targeted intranasal administration. The developed SLNs were synthesized and comprehensively evaluated for biodistribution and pharmacokinetics in mice following nose-to-brain delivery. Drug concentrations in the brain and peripheral tissues were quantified using a robust and validated HPLC method. Therapeutic efficacy was further investigated in an <i>in vivo</i> glioblastoma model established by intracerebral U87MG cell implantation. Tumor progression was monitored via precise volume measurements and survival analysis, while the safety profile was assessed through comprehensive acute and subacute toxicity studies. Pharmacokinetic analysis confirmed effective brain tissue distribution and sustained drug levels. Furthermore, the dual-loaded SLN treatment demonstrated a significant reduction in tumor volume and remarkably extended survival rates compared to the control and conventional treatment groups. Ex vivo pathological evaluations and systemic toxicity studies indicated no mortality or gross organic damage at the tested doses, suggesting an acceptable systemic safety profile under the evaluated conditions. However, further rigorous evaluations regarding local nasal mucosal toxicity and long-term renal accumulation are required to fully establish the safety limits of this carrier system. Overall, intranasally administered SLNs provide a promising nanoparticle-based strategy that offers a viable, low-toxicity alternative to improve clinical outcomes in aggressive brain tumors.\u0000</p></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029369","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":"Single-Step Solvent Evaporation Via Spray-Drying for the Production of Ph-Sensitive Polymeric Nanospheres for Dermatological Applications","authors":"Ana Maria Lenz Cardoso,&nbsp;Bruna Aparecida Souza Machado,&nbsp;Silvia Stanisçuaski Guterres,&nbsp;Henrique Rodrigues Marcelino","doi":"10.1208/s12249-026-03458-8","DOIUrl":"10.1208/s12249-026-03458-8","url":null,"abstract":"<div><p>Polymeric nanospheres are promising drug delivery systems capable of controlling the release of active molecules. However, their inherent colloidal instability necessitates the use of drying techniques to enhance physicochemical stability and microbial resistance. However, conventional multi-step production processes hinder industrial-scale-up due to increased complexity and longer processing times. This work aimed to develop a single-step spray-drying process to obtain Eudragit® L100 nanospheres in powder form, thereby eliminating the need for traditional solvent evaporation, and to investigate the effects of incorporating these nanospheres into hydroxyethyl cellulose gels for dermatological applications. Eudragit® L100 was selected for its controlled release at approximately pH 6.00, facilitating delivery to specific areas, particularly on barrier-disrupted skin. Nanospheres were produced via nanoprecipitation followed by direct spray-drying to reduce production time. The nanosuspension and redispersed dried formulations were characterized by particle size, polydispersity index, morphology, and zeta potential. Before drying, the nanospheres had an average size (Z-average) of 114 nm and a polydispersity index (PdI) of 0.19 and successfully preserved their properties after a single drying step (Z-average = 140 nm and PdI = 0.2). Zeta potential was altered (<i>p</i> &lt; 0.05) but remained high (-23 to -17 mV), indicating electrostatic stabilization. Gel formulations exhibited dose-dependent pseudoplastic behavior, with consistency decreasing proportionally to nanosphere concentration. Finally, moderate to strong correlations were found between rheology and textural analysis. This single-step solvent removal methodology represents a significant manufacturing advancement, offering reduced processing time and costs. The pH-responsive nanospheres showed excellent redispersibility and gel compatibility, establishing their potential as carriers for dermatological systems.</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":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03458-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029380","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":"Modeling Bioactive Release from Cyclodextrin Complex-Loaded Polymeric Films: A Unified Theoretical Framework Integrating Host–Guest Thermodynamics, Partitioning, and Multi-Mechanism Transport","authors":"Pitt Supaphol","doi":"10.1208/s12249-026-03541-0","DOIUrl":"10.1208/s12249-026-03541-0","url":null,"abstract":"<div><p>Bioactive release from polymeric films loaded with cyclodextrin (CD) inclusion complexes couples host–guest equilibrium to multi-species transport. This work establishes the Cyclodextrin–Polymer Film Interactive Release (CPFIR) model, integrating complexation thermodynamics with diffusion, swelling, and erosion. Its central element is the Thermodynamic Eigenrate Decomposition (TED), which reduces each mechanism to a first-order depletion rate in s⁻¹. Because the rates share a dimension, their normalized values are weights that sum to unity and remain non-negative by construction, not by imposed normalization. Flory–Huggins parameters computed from Hansen solubility parameters enter the rates directly and supply a thermodynamic gate that suppresses swelling in hydrophobic matrices. A structural identifiability analysis shows the weights cannot be recovered from release data, because the model depends on the weights and the transport rate constants only through their products; determining them <i>a priori</i> is therefore a logical necessity rather than a convenience, and it supplies a falsification test no empirical model possesses. Retrospective application to two published experimental systems, a β-cyclodextrin nanosponge hydrogel and cyclodextrin-citrate coatings, with the weights computed <i>a priori</i> and held fixed, reproduces the reported release behavior (<i>R</i>² = 0.9952) and the reported mechanistic classification without adjusting any weight. Synthetic case studies across five regimes confirm internal consistency (<i>R</i>² ≥ 0.9955) but test self-consistency, not predictive accuracy. The framework is accordingly semi-predictive: it predicts the mechanism balance and the qualitative form of the profile before any release measurement, whereas the transport constants <i>D</i>_eff,app, <i>λ</i>_relax, and <i>k</i>_e require independent measurement or fitting.</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":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029378","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":"Calcium Carbonate-based Microencapsulation Suppresses Thermal Oxidative Degradation and Enhances the Cellular Activity of Resveratrol","authors":"Gwanyeong Ko,&nbsp;Chan Hee Lee,&nbsp;Yukyung Kim,&nbsp;Dongwon Kim,&nbsp;Ee Taek Hwang","doi":"10.1208/s12249-026-03499-z","DOIUrl":"10.1208/s12249-026-03499-z","url":null,"abstract":"<div><p>Resveratrol is a bioactive polyphenol with well-established antioxidant and anti-inflammatory properties; however, its practical application is severely limited by poor aqueous solubility and rapid degradation under thermal and oxidative conditions. In this study, we developed a calcium carbonate (CaCO₃)-based microencapsulation system (Resvera-CC) to enhance the stability of resveratrol through mineral confinement. The formulation enables efficient loading of resveratrol within CaCO₃ microparticles, forming an inorganic–organic hybrid microcarrier system. Physicochemical characterization demonstrated that encapsulation effectively suppresses thermally accelerated oxidative degradation of resveratrol, as evidenced by significantly improved retention under elevated temperature (45℃) conditions. This stabilization is attributed to protective confinement within the mineral matrix and interfacial interactions, including electrostatic attraction, hydrogen bonding, and Ca²⁺ coordination. <i>In vitro</i> evaluation using human keratinocytes revealed that Resvera-CC exhibits enhanced biological activity compared to dose-matched free resveratrol, as indicated by increased filaggrin (FLG) expression while exhibiting excellent cytocompatibility. The enhanced biological response is associated with improved preservation of molecular integrity following encapsulation. From a practical perspective, the aqueous precipitation process enables controllable particle formation and scalable production. Collectively, these results demonstrate that CaCO₃-based microencapsulation provides an effective strategy to suppress oxidative degradation and preserve the functional performance of labile bioactive compounds, supporting its potential application in functional ingredient stabilization and formulation technologies.\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":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029410","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":"DoE-guided Development of Hydroxypropyl-β-cyclodextrin Complex-loaded Curcuminoid Orodispersible Tablets for Geriatric Use","authors":"Prasopchai Patrojanasophon,&nbsp;Supusson Pengnam,&nbsp;Thapakorn Charoenying,&nbsp;Boonnada Pamornpathomkul,&nbsp;Praneet Opanasopit,&nbsp;Theerada Taesotikul,&nbsp;Prin Chaksmithanont,&nbsp;Chaiyakarn Pornpitchanarong","doi":"10.1208/s12249-026-03544-x","DOIUrl":"10.1208/s12249-026-03544-x","url":null,"abstract":"<div><p>This study aimed to enhance the physicochemical properties of curcuminoids by preparing an inclusion complex and formulate an orodispersible tablet (ODT) suitable for elderly patients. A purified curcuminoid was complexed with hydroxypropyl-β-cyclodextrin (HP-β-CD). A design of experiments was employed to optimize the formulation by investigating the effects of a binder and a superdisintegrant on critical tablet attributes. The final optimized ODT was evaluated for compliance with pharmacopeial standards. The 1:1 molar ratio curcuminoid:HP-β-CD complex was identified as optimal, providing a substantial (214-fold) increase in solubility. The complex demonstrated superior photostability, thermal resistance, and ambient storage stability compared to the uncomplexed curcuminoid. The optimized ODT formulation, exhibited excellent mechanical robustness and achieved a rapid disintegration time of 22.21 ± 1.94 s. <i>In vitro</i> dissolution studies showed enhanced drug release, achieving 97.79 ± 0.66% release at 60 min and demonstrating a distinct dissolution profile compared to a commercial non-complexed formulation. This work presented a rational, dual-strategy formulation approach that combines molecular-level solubility enhancement with dosage form optimization to improve the <i>in vitro</i> performance of curcuminoids. The findings highlight the potential of cyclodextrin-based ODT systems as a scalable platform for delivering poorly soluble phytochemicals, particularly for geriatric and dysphagic populations.</p></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015206","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":"Beyond Immediate Release: FDM-Printed Pediatric 6-Mercaptopurine Chewable Tablets with Spontaneous In Situ Nanostructure Formation","authors":"Gabriel S. Oliveira,&nbsp;Ana Luiza Lima,&nbsp;Pedro Granados Muñoz,&nbsp;Idejan P. Gross,&nbsp;Livia Sa-Barreto,&nbsp;Patrícia Medeiros-Souza,&nbsp;Tais Gratieri,&nbsp;Guilherme M. Gelfuso,&nbsp;Marcilio Cunha-Filho","doi":"10.1208/s12249-026-03556-7","DOIUrl":"10.1208/s12249-026-03556-7","url":null,"abstract":"<div><p>Pediatric maintenance therapy for acute lymphoblastic leukemia requires prolonged daily administration of 6-mercaptopurine (6-MP), a drug characterized by a narrow therapeutic index and substantial interindividual variability, creating a need for flexible and patient-friendly dosage forms. This study aimed to develop pediatric chewable tablets 6-MP using hot-melt extrusion and fused deposition modeling (FDM) 3D printing. Preformulation studies and rheological characterization were performed to support formulation development. The influence of internal architecture on porosity, disintegration, mechanical properties, and chewability was investigated by varying infill density. Among the evaluated architectures, 30% infill provided the best balance between structural integrity, porosity, rapid disintegration, and softening after saliva exposure, ensuring adequate chewability. Tablets exhibited accurate drug content (99.5 ± 2.2%). Beyond their immediate-release behavior, complete drug release was achieved within 15 min, while colloidal nanostructures were spontaneously formed, associating approximately 11% of dissolved 6-MP, suggesting a hybrid release mechanism combining rapid drug availability with nano-mediated modulation. Dynamic light scattering and transmission electron microscopy confirmed these findings. Overall, the developed platform demonstrates the potential of FDM-based structural engineering to produce personalized pediatric medicines and reveals that thermally processed polymeric matrices may function as dynamic drug delivery systems rather than conventional immediate-release dosage forms.</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":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03556-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015226","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":"Terpesomes as Advanced Nanocarriers for Enhanced Drug Delivery: Formulation Strategies, Mechanistic Insights, and Therapeutic Applications","authors":"Anroop B. Nair,&nbsp;Mohamed A. Morsy,&nbsp;Ahmed M. Agiba,&nbsp;Rofida Albash","doi":"10.1208/s12249-026-03550-z","DOIUrl":"10.1208/s12249-026-03550-z","url":null,"abstract":"<div><p>Terpenes have a low potential for irritation and are classified as Generally Recognized as Safe (GRAS) chemicals. Terpenes possess favorable biological properties that support their use in drug delivery. Some terpenes and essential oils have been encapsulated in nanostructured systems called terpesomes to overcome their chemical instability. Compared to conventional vesicles, terpesomes are new vesicular structures that showed greater membrane penetration. The capacity of terpesomes to increase permeability across membranes while decreasing systemic absorption is one of their main benefits. Terpesomes enhance drug permeation by improving membrane interaction and increasing drug transport across biological barriers. The structure, characterization, penetration processes, and applications of terpesomes are all addressed in this review. Overall, this review highlights that the enhanced penetration capability of terpesomes makes them promising lipid vesicular carriers for a wide range of pharmaceutical applications.</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":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015194","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":"Detecting Crystallization in Spray-dried Amorphous Solid Dispersion Tablets Administered in Apple Sauce: Feasibility, Challenges and Considerations","authors":"Paroma Chakravarty,&nbsp;Minhthi Bui,&nbsp;Kellie K. Sluga,&nbsp;Bifan Chen,&nbsp;Simon Chan,&nbsp;Hao Helen Hou","doi":"10.1208/s12249-026-03554-9","DOIUrl":"10.1208/s12249-026-03554-9","url":null,"abstract":"<div><p>GENE-A, a small molecule classified as a BCS Class IV compound, was formulated as a spray dried amorphous solid dispersion (SDD) using HPMC-AS polymer for oral delivery and compressed with additional excipients to yield tablets. Owing to a high clinical daily dose projection, the possibility of administering multiple tablets in applesauce was explored for patient compliance. Since GENE-A crystallized to a hydrate in aqueous media in previously conducted solubility studies, dispersion of SDD tablets in applesauce (aqueous medium) necessitated the development of an analytical method to detect low levels of crystallinity in these mixtures. Using transmission PXRD and multistep sample preparation procedure, a calibration curve was obtained by employing powder blends with matching composition as SDD tablets, spiked with different amounts of crystalline hydrate, dispersed in applesauce. From this curve, the limits of detection and quantitation of crystalline active in these samples were determined to be 1.8 and 4.9% respectively. A 8.5–12% error of prediction for % crystallinity was obtained for validation samples which may be attributed primarily to sample preparation challenges such as retention of water in the centrifuged samples. Using this method, % crystallinity was determined to be &lt; LOD in the test samples, i.e. film coated SDD tablets (for clinical use) dispersed in applesauce at T = 0 and 2 h. Our study is the first to demonstrate the development of a PXRD based method for detecting low levels of crystallinity in a semi-solid matrix to monitor physical stability of an active in drug-vehicle mixtures.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><img></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015187","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":"Photothermally Induced Vapor Nanobubbles Enable Disruption and Antibiotic-Improved Responsiveness in Uropathogenic Biofilms","authors":"Júlia Alcàcer-Almansa,&nbsp;Amin Ahmad,&nbsp;Kevin Braeckmans,&nbsp;Núria Blanco-Cabra,&nbsp;Samuel Sánchez,&nbsp;Eduard Torrents,&nbsp;Juan C. Fraire","doi":"10.1208/s12249-026-03524-1","DOIUrl":"10.1208/s12249-026-03524-1","url":null,"abstract":"<div><p>Treating bacterial biofilms remains a major clinical challenge, particularly in uropathogenic infections where the dense extracellular matrix impedes antibiotic access and protects tolerant bacterial populations. In this work, we explored a nanomaterial-based strategy to improve antibiotic responsiveness by combining iron oxide nanoparticles (IONPs) with pulsed laser irradiation to induce vapor nanobubble (VNB)-mediated disruption of a mature flow-grown uropathogenic <i>E. coli</i> CFT073 biofilm. We tested three nanoparticle sizes (70 nm, 130 nm, and 500 nm) and identified IONP₅₀₀ as the most effective formulation for generating VNBs upon irradiation with 532 nm nanosecond laser pulses, with a VNB threshold of 0.56 J/cm² per pulse. In the mature biofilm model, the combined IONP₅₀₀ + ciprofloxacin + laser treatment significantly enhanced antibiotic activity compared with ciprofloxacin alone, increasing dead biomass from approximately 16% to 23%, corresponding to a 39–45% relative increase, as quantified by COMSTAT analysis and one-way ANOVA with Tukey’s post-hoc test. The combined treatment also reduced total biofilm biomass and increased biofilm porosity by 55.8% compared with ciprofloxacin alone, supporting a mechanism based on VNB-mediated matrix disruption and improved antibiotic access. Overall, these results support the use of photothermally active, biocompatible IONPs as a promising complementary strategy to enhance the efficacy of conventional antibiotics against persistent biofilm-associated infections.</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/s12249-026-03524-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148986550","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}