International Journal of Pharmaceutics最新文献

{"title":"LGA-PEI nanoparticles enable efficient nucleic acid delivery to primary murine T cells.","authors":"Priscila Tonon Baschirotto, Christian Marín-Müller, Randall Loaiza-Montoya","doi":"10.1016/j.ijpharm.2026.127584","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127584","url":null,"abstract":"<p><p>Non-viral engineering of primary T cells is constrained by low transfection efficiency and significant cargo-induced toxicity. This study evaluates a LGA-PEI (lactic-co-glycolic acid-modified polyethyleneimine) nanoparticle system designed to overcome the recalcitrance of murine T cells, particularly unstimulated, murine T cells. We characterized LGA-PEI polyplexes for size, surface charge, and pH-dependent stability, noting rapid disassembly at pH 5.0 to facilitate endosomal escape. Optimization of nanoparticle concentrations enabled transfection efficiencies of 16.5 % in CD3-sensitized T cells and 30.0 % in stimulated primary mouse T cells, maintaining high viability (85 %). Mechanistic analysis suggests that cell death is primarily driven by initial membrane disruption rather than post-internalization metabolic stress. We identified a direct correlation between the number of internalized plasmids and GFP expression, confirming efficient post-internalization events. LGA-PEI-mediated delivery of shRNA targeting Sorcin achieved significant gene knockdown. Transfection with LGA-PEI-encapsulated scrambled control plasmids (shRNA) exhibited increased CD25 and FoxP3 marker expression, along with cytokine production alterations. These findings demonstrate that the LGA-PEI platform provides a high-efficiency, low-toxicity alternative for T cell modulation, though the observed phenotypic alterations necessitate careful immunotoxicity screening in therapeutic applications.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127584"},"PeriodicalIF":6.0,"publicationDate":"2026-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic stratum corneum ceramide alterations reflect barrier dysfunction and clinical response to topical chlormethine treatment in early-stage mycosis fungoides.","authors":"Catherine Mergen, Selinde S Wind, Elise S M Beljaards, Rianne Rijneveld, Mick van Schaick, Joke A Bouwstra, Manon Jansen, Naomi Klarenbeek, Tessa Niemeyer-van der Kolk, Rob J Vreeken, Jeroen van Smeden, Abdoel El Ghalbzouri, Thomas Hankemeier, Koen D Quint, Maarten H Vermeer, Robert Rissmann, Jannik Rousel","doi":"10.1016/j.ijpharm.2026.127593","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127593","url":null,"abstract":"<p><p>Early-stage mycosis fungoides (MF), a cutaneous T-cell lymphoma, presents as patches and/or plaques with an impaired skin barrier. The stratum corneum (SC) lipid matrix is important for skin barrier function. Alterations in the SC ceramide profile have been linked to a reduced barrier function in benign inflammatory skin diseases and might also be an underlying factor in the impaired barrier function in MF. Therefore, we characterized barrier function and SC ceramide profiles in lesional and non-lesional skin of 21 patients with early-stage MF and 10 healthy controls, and assessed how these barrier and ceramide characteristics evolve during chlormethine gel treatment in patients. Barrier function was measured by transepidermal water loss. SC ceramides were collected by tape stripping and analyzed by liquid chromatography-mass spectrometry. Local inflammatory markers were measured in suction blister fluid. At baseline, MF lesions showed impaired barrier function accompanied by distinct changes in the SC ceramide profile, including altered ceramide subclass composition and reduced ceramide chain length. These abnormalities occurred in the context of a predominantly type 1-skewed inflammatory milieu. Importantly, both barrier dysfunction and ceramide alterations were dynamic and improved in patients with a clinical response to chlormethine gel treatment, alongside reduced lesion severity and local inflammation. Longitudinal associations of ceramide characteristics with barrier function, clinical lesion severity, and inflammatory markers support SC ceramide alterations as dynamic correlates of MF disease activity. Together, these findings suggest that SC ceramide alterations may reflect a downstream consequence of inflammation that is shared across inflammatory dermatoses.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127593"},"PeriodicalIF":6.0,"publicationDate":"2026-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calixarene-based nanocarrier for ciprofloxacin and curcumin: evaluation of antibacterial, antibiofilm, antioxidant and anti-inflammatory activities.","authors":"Loredana Ferreri, Lucia Cambria, Giovanna Ginestra, Maria Fernanda Taviano, Giuseppe Granata, Ludovica Maugeri, Giovanna Calabrese, Benedetta Galletta, Sonia Pedotti, Valeria Consoli, Luca Vanella, Salvatore Petralia, Antonia Nostro, Grazia Maria Letizia Consoli","doi":"10.1016/j.ijpharm.2026.127597","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127597","url":null,"abstract":"<p><p>Drug delivery and multidrug therapy are essential research fields in the fight against complex diseases, including infections. Here, we investigated the capability of a polyanionic nanocarrier, formed through the spontaneous self-assembly of an amphiphilic p-sulfonate-calix[4]arene derivative, to load ciprofloxacin and curcumin, both individually and in combination, using a simple and reproducible organic solvent-free method. Entrapment in the nanocarrier enhanced the aqueous solubility and stability of both ciprofloxacin and curcumin and protected them from UV light-induced photodegradation. The supramolecular nanosized assemblies exhibited antibacterial activity against Gram-positive (S. aureus ATCC 6538) and Gram-negative (Escherichia coli ATCC 10536, P. aeruginosa ATCC 9027) bacteria, including antibiotic-resistant strains (S. aureus (MRSA) ATCC 43300, S. aureus 1199B, Enterococcus faecium DSM 17050, Acinetobacter baumannii DSM 106838, E. coli DSM 105388, and P. aeruginosa DSM 102273). Against S. aureus 1199B, the nanoassemblies reduced biofilm formation, an effect largely attributable to the empty nanocarrier, and were effective against mature biofilms. The antioxidant activity of curcumin was preserved following its incorporation into the nanocarrier, as demonstrated by its DPPH radical scavenging activity. Additionally, the nanoassemblies loaded with ciprofloxacin and curcumin showed anti-inflammatory effects, as evidenced by the reduced TNF-α levels in LPS-stimulated eukaryotic cells. The multifunctional nature of the nanoassemblies highlights their potential for combining antimicrobial, radical-scavenging and anti-inflammatory properties, offering a promising approach to addressing the complex challenges associated with bacterial infections, including those involving biofilms.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127597"},"PeriodicalIF":6.0,"publicationDate":"2026-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of the protein corona in RGD-functionalized nanoliposomes delivering enzymatic replacement therapy for Fabry disease.","authors":"Marc Moltó-Abad, Judit Tomsen-Melero, Verónica Villagrasa-Araya, Daniel Marijuan-Pinel, Zamira V Díaz-Riascos, Francesc Canals, Luna Martín, Guillem Pintos-Morell, Sandra Mancilla, Belén García, Aida Carreño, Albert Font, Simó Schwartz, Roser Ferrer, Nora Ventosa, Elisabet González-Mira, Ibane Abasolo","doi":"10.1016/j.ijpharm.2026.127582","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127582","url":null,"abstract":"<p><p>The protein corona (PC) formed upon nanoparticle exposure to blood critically defines their biological identity and in vivo fate, yet its impact on targeted liposomal enzyme replacement therapies (ERTs) remains incompletely understood. Here, we systematically investigated how RGD functionalization (including varying ligand densities) and α-galactosidase A (GLA) loading influence PC composition, cellular uptake, and biodistribution using a panel of liposomal formulations with and without targeting ligands and therapeutic cargo. Quantitative proteomics revealed that both RGD functionalization and GLA loading reshape the PC by enriching key opsonins (e.g., C3 and IgG subclasses) together with dysopsonins (such as apolipoproteins and albumin), generating distinct and balanced immune signatures. Notably, RGD promoted complement recruitment, indicating increased immune recognition potential. In vitro, RGD functionalization significantly enhanced endothelial uptake even in the presence of a pre-formed PC, demonstrating that targeting functionality is modulated but not abolished by corona formation. In vivo, GLA-loaded liposomes increased enzymatic activity in plasma and tissues compared to free GLA, and higher RGD density enhanced delivery to liver, spleen, kidney, and heart, albeit with reduced plasma persistence. All GLA-loaded formulations showed brain-associated enzymatic activity in perfused brain tissue. Additional capillary-depletion analysis indicated that, at 30 min after administration, the measurable signal was predominantly associated with the cerebrovascular fraction, that could be potentially linked to coronas enriched in ApoE, transferrin, and transthyretin. Together, these findings support a hybrid model in which the protein corona modulates, rather than masks, targeting ligands through a balanced opsonin/dysopsonin profile. This work provides mechanistic insight into how nanoparticle surface properties and biological identity interplay, offering general design principles for optimizing targeted nanomedicines beyond liposomal ERT.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127582"},"PeriodicalIF":6.0,"publicationDate":"2026-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transferrin functionalization enhances prostate cancer cell uptake and cytotoxicity of cabazitaxel-loaded polymeric nanoparticles.","authors":"João Vito Barroso de Freitas, Victória Meira Holanda, Alex Bruno Matos de França, Thais da Silva Moreira, Ana Carolina Cruz de Souza, Beatriz Alves Juvêncio, Alyne Rodrigues de Araujo Nobre, Fábio de Oliveira da Silva Ribeiro, Raquel Petrilli, Josimar O Eloy","doi":"10.1016/j.ijpharm.2026.127583","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127583","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Prostate cancer (PCa) is the second most common cancer in men worldwide, and chemotherapeutic treatment may exhibit limited efficacy owing to side effects and hypersensitivity. Cabazitaxel (CTX) is an antineoplastic agent used to treat prostate cancer; however, it has low selectivity and adverse effects that limit its adherence and efficacy. In this context, transferrin (Tf)-functionalized polymeric nanoparticles have emerged as a potential targeted therapy directed toward the Tf receptor (TfR), which is overexpressed in prostate cancer cells. In this study, cabazitaxel was encapsulated in polycaprolactone (PCL) polymeric nanoparticles functionalized with transferrin (Tf), and its in vitro activity was evaluated in PCa cell lines. Therefore, a study was conducted to determine the optimal preparation conditions in terms of formulation characteristics. The nanoparticles were produced by nanoprecipitation using acetone as the solvent in the presence of the surfactant Poloxamer 188. Transferrin was covalently bound to the PEG-PCL-maleimide moiety on the nanoparticle surface. The transferrin-functionalized nanoparticles had an average particle size of 123.9 nm ± 1.13, a polydispersity index (PDI) of 0.168 ± 0.11, a zeta potential of -11.43 mV ± 1.89, and an encapsulation efficiency (EE%) of 79.6% ± 6.8. In electrophoresis, free transferrin exhibited a band near 80 kDa, with a corresponding band observed in the elution of the functionalized nanoparticles, indicating protein attachment to the nanoparticles. Circular dichroism analysis, together with fluorescence spectroscopy, demonstrated the preservation of protein structural integrity after conjugation. Microscopy techniques (SEM and AFM) revealed the spherical morphology of the nanoparticles, and AFM further confirmed successful conjugation through changes in the surface roughness of the functionalized nanoparticles. The in vitro release study demonstrated that both non-functionalized and transferrin-functionalized PCL-based nanoparticles provided a sustained release of cabazitaxel over 192 h, confirming the potential of these systems for prolonged drug delivery. In cell culture assays, the high cell viability observed in the L929 cell line demonstrated the safety of the developed systems, whereas the marked reduction in viability in DU145 and PC3 cell lines demonstrated the effect of encapsulation on cytotoxicity of the developed systems. Functionalization with transferrin (Tf) significantly increased the in vitro toxicity and cellular internalization. The percentage of cellular internalization was higher in the PC3 cell line than in the DU145 cell line, corroborating the literature reporting higher TfR expression in this lineage. Encapsulation and functionalization demonstrated potential as active drug-targeting vectors, as they increased cytotoxicity compared to free drugs. This finding represents an important advancement in the development of a formulation and approach capable of enhancing ","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127583"},"PeriodicalIF":6.0,"publicationDate":"2026-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-viral delivery and genome editing for CAR-NK engineering in solid tumors: from ex vivo manufacturing to in vivo reprogramming.","authors":"Yidan Shen, Xiaoye Ye, Siyuan Shen, Fei Lv","doi":"10.1016/j.ijpharm.2026.127580","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127580","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR)-engineered natural killer (NK) cell therapy has emerged as a promising immunotherapeutic strategy for cancer treatment, offering advantages over CAR-T cells such as a lower risk of cytokine release syndrome and graft-versus-host disease and the potential for off-the-shelf manufacturing. Viral vectors have long served as effective tools for CAR-NK engineering, but their dependence on complex manufacturing procedures, considerable production costs, and the potential risks associated with genomic integration has encouraged increasing interest in non-viral alternatives. Recent advances in genetic engineering technologies have facilitated the development of CAR-NK platforms, particularly through non-viral delivery approaches including electroporation, transposon systems and lipid nanoparticles, while CRISPR-based tools enable targeted genome editing. Meanwhile, an increasing number of clinical trials have begun to evaluate the safety and therapeutic potential of CAR-NK cells in both hematological malignancies and solid tumors. However, challenges such as limited NK-cell persistence, antigen heterogeneity, and the immunosuppressive tumor microenvironment remain. In this review, we summarize recent progress in non-viral CAR-NK engineering strategies, analyze the current landscape of preclinical and clinical trials, and discuss key challenges and future directions for advancing CAR-NK therapy. Collectively, these advances suggest that non-viral engineering technologies may serve as an important technological foundation for next-generation CAR-NK therapies, enabling more flexible ex vivo manufacturing and potentially supporting the future development of in vivo CAR-NK generation strategies for solid tumors.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127580"},"PeriodicalIF":6.0,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cascade liposomal delivery for glioblastoma through multi-stage biological checkpoints.","authors":"Yanyu Zhang, Shaocong Weng, Qihui Zhang, Yijun Dong, Qingfeng Wu, Tingting Hu, Zhiyong Guo, Xiaoyi Wang","doi":"10.1016/j.ijpharm.2026.127552","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127552","url":null,"abstract":"<p><p>Although receptor-targeted liposomes provide promising opportunities for glioblastoma therapy, their clinical translation remains limited by sequential biological barriers encountered after systemic administration. Here, we establish a multi-stage checkpoint framework linking carrier properties with stage-specific transport constraints, including systemic clearance, BBB/BTB heterogeneity, extracellular matrix resistance, and myeloid sequestration. We analyze receptor-mediated transcytosis through a mechanistic triad of ligand engagement, intracellular sorting, and abluminal release, highlighting the binding-site barrier and affinity paradox that restrict effective parenchymal delivery. Successful transcytosis represents only the initial step and we further develop a cascade targeting framework integrating tissue penetration, tumor cell recognition, and intracellular payload availability. Key translational challenges, including tumor microenvironment modulation, Quality by Design (QbD) manufacturing, safety, and companion diagnostics, are critically examined. Future progress will depend on evaluating liposomal platforms according to productive cellular exposure, with bulk accumulation serving only as a supporting measure, and on using quantitative transport profiling and imaging-guided stratification to identify patients whose biological barriers are compatible with specific liposomal designs.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127552"},"PeriodicalIF":6.0,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Albumin/BSH-fused nanoparticle for boron neutron capture therapy of esophageal squamous cell carcinoma.","authors":"Hui-Min Qin, Ren-Wei Cai, Yu-Jing He, Jian Zhang, Xing-Lin Su, Yu-Ling Kan, Bao-Sheng Li, Xun Li","doi":"10.1016/j.ijpharm.2026.127602","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127602","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignant tumor which suffers from poor prognosis and limited therapeutic remedies. As a physiologically-oriented radiotherapy and highly tumor-specific modality, boron neutron capture therapy (BNCT) shows great potential for the treatment of ESCC. Since efficacy of BNCT is critically restricted to boron drugs, novel boron agents with satisfactory boron load and intracellular uptake are highly demanded. Herein, we developed a novel albumin/BSH-conjugated nanoparticle (BSH@Alb) as a safe and effective boron agent. It resulted BSH@Alb displayed uniform particle size, high encapsulation efficiency (93.1 ± 0.39%), loading capacity (15.52 ± 0.41%) and good stability in different solution (water, PBS and plasma). Collectively, BSH@Alb significantly enhanced intracellular boron accumulation and showed acceptable cytocompatibility in comparison with prototype BSH, supporting its potential value for BNCT therapy as a promising boron-delivery candidate.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127602"},"PeriodicalIF":6.0,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards rational carrier engineering: a review of interfacial binding, release mechanisms, and active delivery systems.","authors":"Gomaa Farouk Elfawal, Anita Eckstein Andicsová, Alena Opálková Šišková","doi":"10.1016/j.ijpharm.2026.127566","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127566","url":null,"abstract":"<p><p>Controlled release of active materials from carrier systems supports technologies spanning pharmaceuticals, agrochemicals, cosmetics, and functional food products. Despite decades of research, the field remains fragmented: studies on physicochemical binding, release kinetics, and carrier architecture are often reported in isolation, making it difficult to translate mechanistic insight into analytical design rules. This review provides an integrated framework connecting the physicochemical interactions governing active-carrier binding. It illustrates the core mechanisms that dictate release (such as diffusion, swelling, degradation, and stimuli-triggered pathways). We also examine how carrier structural features modulate these mechanisms and ultimately determine release kinetics. We pay particular attention to the characterization techniques used to quantify release behavior, including in vitro testing methodologies, which remain a critical yet inconsistently standardized foundation for comparing carrier systems across studies. We also distinguish generalizable design principles from application-specific constraints, showing how carrier properties and release mechanisms translate across pharmaceutical, agrochemical, cosmetic, food, and environmental contexts.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127566"},"PeriodicalIF":6.0,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From ecosystem engineering to living computers: integrating dual-paradigm bacterial therapeutics for solid tumor microenvironment reprogramming.","authors":"Alaa Elmetwalli, Naseh A Algehainy, Faisal H Altemani, Mohammad A Alanazi, Abdullah H Altemani","doi":"10.1016/j.ijpharm.2026.127586","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127586","url":null,"abstract":"<p><p>Recent advances in tumor microbiome biology and synthetic biology have made bacteria attractive therapeutic agents capable of reprogramming tumor-associated microbial ecosystems and serving as programmable living systems in solid tumors. In this review, we construct a dual-paradigm framework combining engineered bacterial therapeutics and ecosystem editing. In the first paradigm, phage-mediated targeting, competitive displacement, and metabolic reprogramming are used to alter tumor-associated microbial communities. In the second paradigm, engineered bacteria are equipped with environmental sensors, genetic logic circuits, and therapeutic payloads. We discuss the mechanistic interplay of these strategies in terms of ecological niche formation, bacterial colonization, immune and metabolic remodeling, and microbiome-host feedback. Clinical experience still varies across platforms due to differences in bacterial strain, attenuation, route of administration, tumor biology, treatment context, and patient characteristics. Major translational challenges include biocontainment, genetic stability, manufacturing and potency control, predictive biomarker validation, and product-specific regulatory requirements. We propose an additional hypothesis-generating framework for patient stratification and adaptive treatment monitoring. These concepts together provide a structured framework for exploring bacterial therapeutics as components of precision oncology, while highlighting the need for prospective clinical validation.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127586"},"PeriodicalIF":6.0,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}