Nanoparticles (NPs) are emerging candidates in cancer management. Currently, they are extensively employed in biomedical applications, including drug delivery, imaging, sensing, gene therapy, photothermal therapy, photodynamic therapy, radiation therapy, immunotherapy, and magnetic hyperthermia, among others, for cancer management. Aggregating prone-to-aggregate NPs at the targeted site will help reduce off-target side effects and improve the efficacy of NPs. This diversity in NP applications is due to their dynamic surface properties, which allow their desired modifications for the intended application. Present NP research focuses on improving the efficacy of NPs by concentrating their distribution at the tumor site. This review discusses the prone-to-aggregate NPs aggregation approach to attain selective delivery at the tumor site following various stimuli (pH, enzyme, redox environment, temperature, interstitial fluid, magnetic field, light, etc.). Furthermore, this review also discusses the therapeutic and diagnostic applications of the prone-to-aggregate NPs aggregation approach in cancer therapy.
{"title":"Prone-to-aggregate nanoparticle for cancer-targeted drug delivery","authors":"Manisha Choudhary , Dnyaneshwar Kalyane , Devendra Choudhary , Nupur Vasdev , Muktika Tekade , Pinaki Sengupta , Rakesh Kumar Tekade","doi":"10.1016/j.ijpharm.2026.126600","DOIUrl":"10.1016/j.ijpharm.2026.126600","url":null,"abstract":"<div><div>Nanoparticles (NPs) are emerging candidates in cancer management. Currently, they are extensively employed in biomedical applications, including drug delivery, imaging, sensing, gene therapy, photothermal therapy, photodynamic therapy, radiation therapy, immunotherapy, and magnetic hyperthermia, among others, for cancer management. Aggregating prone-to-aggregate NPs at the targeted site will help reduce off-target side effects and improve the efficacy of NPs. This diversity in NP applications is due to their dynamic surface properties, which allow their desired modifications for the intended application. Present NP research focuses on improving the efficacy of NPs by concentrating their distribution at the tumor site. This review discusses the prone-to-aggregate NPs aggregation approach to attain selective delivery at the tumor site following various stimuli (pH, enzyme, redox environment, temperature, interstitial fluid, magnetic field, light, etc.). Furthermore, this review also discusses the therapeutic and diagnostic applications of the prone-to-aggregate NPs aggregation approach in cancer therapy.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126600"},"PeriodicalIF":5.2,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029550","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}
Pub Date : 2026-02-20Epub Date: 2025-12-25DOI: 10.1016/j.ijpharm.2025.126534
Ayyah Abdoh , Mohammad Imran , Khadeejeh Al-Smadi , Harsimran Kaur , Masood Ali , Tushar Kumeria , Yousuf Mohammed
Nanomaterials have improved skin drug delivery by facilitating the creation of smart, stimuli-responsive nanocarriers with increased therapeutic effectiveness. Internal or external stimuli can activate these systems, enabling controlled drug release. Internal stimuli-responsive nanocarriers use pathological alterations in diseased skin, like variations in pH, oxidative stress, enzymatic activity, or glucose concentrations, to trigger drug release exactly at the target sites. Conversely, external stimuli-responsive systems depend on physical stimuli such as temperature, light, electric fields, ultrasound, or magnetic fields, facilitating controlled release at specific times and sites. Collectively, these methods increase localized therapeutic precision, reduce systemic adverse effects, and improve therapeutic outcomes in dermatology. This review explores stimuli-responsive nanocarriers, focusing specifically on their use in skin drug delivery, highlighting their therapeutic advantages and limitations, and summarizing several studies using single- and dual-stimuli responsive systems for skin delivery in the treatment of dermatological disorders. The review also provides a critical overview of the analytical methods used to evaluate these nanocarriers, including in vitro, ex vivo, and in vivo models; physiochemical characterization; and advanced microscopic imaging, it also outlines their advantages and limitations. Finally, the paper concludes by delineating the present status of the field and identifying key challenges for future research to enhance the therapeutic use of stimuli-responsive nanocarriers for skin drug delivery.
{"title":"Stimuli-responsive smart nanocarriers for skin drug delivery","authors":"Ayyah Abdoh , Mohammad Imran , Khadeejeh Al-Smadi , Harsimran Kaur , Masood Ali , Tushar Kumeria , Yousuf Mohammed","doi":"10.1016/j.ijpharm.2025.126534","DOIUrl":"10.1016/j.ijpharm.2025.126534","url":null,"abstract":"<div><div>Nanomaterials have improved skin drug delivery by facilitating the creation of smart, stimuli-responsive nanocarriers with increased therapeutic effectiveness. Internal or external stimuli can activate these systems, enabling controlled drug release. Internal stimuli-responsive nanocarriers use pathological alterations in diseased skin, like variations in pH, oxidative stress, enzymatic activity, or glucose concentrations, to trigger drug release exactly at the target sites. Conversely, external stimuli-responsive systems depend on physical stimuli such as temperature, light, electric fields, ultrasound, or magnetic fields, facilitating controlled release at specific times and sites. Collectively, these methods increase localized therapeutic precision, reduce systemic adverse effects, and improve therapeutic outcomes in dermatology. This review explores stimuli-responsive nanocarriers, focusing specifically on their use in skin drug delivery, highlighting their therapeutic advantages and limitations, and summarizing several studies using single- and dual-stimuli responsive systems for skin delivery in the treatment of dermatological disorders. The review also provides a critical overview of the analytical methods used to evaluate these nanocarriers, including <em>in vitro</em>, <em>ex vivo</em>, and <em>in vivo</em> models; physiochemical characterization; and advanced microscopic imaging, it also outlines their advantages and limitations. Finally, the paper concludes by delineating the present status of the field and identifying key challenges for future research to enhance the therapeutic use of stimuli-responsive nanocarriers for skin drug delivery.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126534"},"PeriodicalIF":5.2,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846692","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}
Activation modulated stimuli-responsive systems (AMS), commonly known as raft-forming systems (RFS), are an innovative platform within gastroretentive drug delivery technologies. These pH-triggered systems transform orally administered liquids from sol to a low-density, viscous floating gel or “raft” by ionotropic gelation upon contact with gastric-ions. Typically, composed of smart hydrophilic polymers, effervescent, and cross-linking agents, AMS stay buoyant in stomach and release drugs instantly in response to physiological stimuli to meet urgent clinical needs. These systems are especially valuable for drugs targeting local gastric action, reducing systemic exposure. AMS can be custom-designed to release therapeutic agents that exhibit high solubility or good stability in response to acidic conditions in stomach to maximize bioavailability. Owing to the strategic location, proximal to absorption window and ability to control release in stomach, AMS has the proven potential to improve the absorption of several therapeutics. AMS can be tailored to modulate microenvironment pH and thereby enhance delivery of drugs that exhibit solubility or stability challenges in an acidic milieu. This review is an attempt to offer an entirely new dimension to the composition, formulation strategies, evaluation techniques, and applications of AMS. Recent advances include development of systems comprising smart polymers that respond to specific physiological stimuli, multi-responsive systems, nanotechnology-integrated, and 3D printed systems. Despite challenges in formulation stability, scale-up, and reproducibility, these systems have generated considerable regulatory and commercial interest globally. Thus, AMS have emerged as a unique and innovative platform with high translational potential to leverage immense clinical benefits of diverse therapeutic agents.
{"title":"Activation-modulated stimuli-responsive systems: an intelligent platform for site-specific gastroretentive delivery of diverse therapeutic agents","authors":"H.N. Shivakumar , Rushikesh Shinde , Vanita Somasekhar , M.G. Hariprasad , N.M. Mahesh","doi":"10.1016/j.ijpharm.2026.126599","DOIUrl":"10.1016/j.ijpharm.2026.126599","url":null,"abstract":"<div><div>Activation modulated stimuli-responsive systems (AMS), commonly known as raft-forming systems (RFS), are an innovative platform within gastroretentive drug delivery technologies. These pH-triggered systems transform orally administered liquids from sol to a low-density, viscous floating gel or “raft” by ionotropic gelation upon contact with gastric-ions. Typically, composed of smart hydrophilic polymers, effervescent, and cross-linking agents, AMS stay buoyant in stomach and release drugs instantly in response to physiological stimuli to meet urgent clinical needs. These systems are especially valuable for drugs targeting local gastric action, reducing systemic exposure. AMS can be custom-designed to release therapeutic agents that exhibit high solubility or good stability in response to acidic conditions in stomach to maximize bioavailability. Owing to the strategic location, proximal to absorption window and ability to control release in stomach, AMS has the proven potential to improve the absorption of several therapeutics. AMS can be tailored to modulate microenvironment pH and thereby enhance delivery of drugs that exhibit solubility or stability challenges in an acidic milieu. This review is an attempt to offer an entirely new dimension to the composition, formulation strategies, evaluation techniques, and applications of AMS. Recent advances include development of systems comprising smart polymers that respond to specific physiological stimuli, multi-responsive systems, nanotechnology-integrated, and 3D printed systems. Despite challenges in formulation stability, scale-up, and reproducibility, these systems have generated considerable regulatory and commercial interest globally. Thus, AMS have emerged as a unique and innovative platform with high translational potential to leverage immense clinical benefits of diverse therapeutic agents.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126599"},"PeriodicalIF":5.2,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075290","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}
Pub Date : 2026-02-20Epub Date: 2026-01-21DOI: 10.1016/j.ijpharm.2026.126616
Patrícia Weimer , Isabella Morel Bordignon , Alexandre Rolim Mineto , Karen de Oliveira Araujo , Júlia Cordeiro Waszak , Nathalya Tesch Brazil , Fabrício Mezzomo Collares , Maria Dul , Rochele Cassanta Rossi , Letícia Scherer Koester
This study examines transdermal delivery of a β-caryophyllene (a lipophilic and volatile compound) loaded nanoemulsion from dissolving water-soluble polymer microneedles (microneedle array patches − MAPs). Development of this system was guided by the principles of Quality by Design; after defining a quality target product profile and critical quality attributes, a rational experimental plan optimized a formulation to maximize the β-caryophyllene content in MAPs. The optimized formulation consists of polyvinyl pyrrolidone combined with polyvinyl alcohol (combination ratio of 1.54) and a β-caryophyllene-to-polymer mass ratio of 0.09. The β-caryophyllene content was maintained higher than 95 % in relation to the additional mass following the micromolding process and after 45 days of storage. In vitro skin insertion, dissolution, mechanical properties, and transdermal delivery have been investigated for the prototype. A key feature of this work is demonstrating the feasibility of delivering a volatile compound through MAP by associating it with a nanoemulsion. This combined delivery method allows for the transdermal administration of β-caryophyllene, which cannot be achieved through topical nanoemulsion application alone. Overall, the developed system offers a promising alternative to traditional topical and oral pharmaceutical dosage forms.
{"title":"Development of dissolving microneedles using a quality by design approach for transdermal delivery of the nanoemulsified volatile compound β-caryophyllene","authors":"Patrícia Weimer , Isabella Morel Bordignon , Alexandre Rolim Mineto , Karen de Oliveira Araujo , Júlia Cordeiro Waszak , Nathalya Tesch Brazil , Fabrício Mezzomo Collares , Maria Dul , Rochele Cassanta Rossi , Letícia Scherer Koester","doi":"10.1016/j.ijpharm.2026.126616","DOIUrl":"10.1016/j.ijpharm.2026.126616","url":null,"abstract":"<div><div>This study examines transdermal delivery of a β-caryophyllene (a lipophilic and volatile compound) loaded nanoemulsion from dissolving water-soluble polymer microneedles (microneedle array patches − MAPs). Development of this system was guided by the principles of Quality by Design; after defining a quality target product profile and critical quality attributes, a rational experimental plan optimized a formulation to maximize the β-caryophyllene content in MAPs. The optimized formulation consists of polyvinyl pyrrolidone combined with polyvinyl alcohol (combination ratio of 1.54) and a β-caryophyllene-to-polymer mass ratio of 0.09. The β-caryophyllene content was maintained higher than 95 % in relation to the additional mass following the micromolding process and after 45 days of storage. In vitro skin insertion, dissolution, mechanical properties, and transdermal delivery have been investigated for the prototype. A key feature of this work is demonstrating the feasibility of delivering a volatile compound through MAP by associating it with a nanoemulsion. This combined delivery method allows for the transdermal administration of β-caryophyllene, which cannot be achieved through topical nanoemulsion application alone. Overall, the developed system offers a promising alternative to traditional topical and oral pharmaceutical dosage forms.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126616"},"PeriodicalIF":5.2,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040763","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}
Pub Date : 2026-02-20Epub Date: 2026-01-22DOI: 10.1016/j.ijpharm.2026.126617
Ryan Fauzy , Fatimah Aqilah Az Zahro , Vania Maharani , Zaizafun Faiha , Angela Bilqisth , Syaiful Choiri
Psoriasis is a chronic autoimmune disorder characterized by persistent inflammation that progressively impairs the quality of life. Conventional corticosteroids suppress inflammatory mediators but fail to inhibit immune cell activation, leading to chronicity and long-term adverse effects. Quercetin and naringenin exhibit potent and synergistic antioxidant and anti-inflammatory properties, but their efficacy is hindered by low solubility and permeability. This study developed a quercetin–naringenin nanoemulsion hydrogel patch (NE–QNH) decorated with a hyaluronate–phospholipid complex (HA–PC) and modified with thermoresponsive polymers for targeted and controlled delivery. The nanoemulsion was optimized using a 22 factorial design based on critical quality attributes, including droplet size, polydispersity index, zeta potential, and encapsulation efficiency (EE). Hydrogel patches with varying polymer were evaluated for viscosity, drying time, spreadability, and elasticity. Ex-vivo permeation studies were conducted using porcine skin, and in-vivo efficacy was confirmed in a psoriasis model to validate the therapeutic outcome. The optimized NE–QNH exhibited a particle size of 14.94 ± 0.06 nm, a zeta potential of –9.78 ± 0.20 mV, an effective EE exceeding 80%, and high stability. The HA–PC complex decorated 87% of the nanoemulsion surface, while polymer modification formed an external matrix. Ex-vivo and in-vivo studies demonstrated a 240% increase in permeation and a 290% improvement in retention, epidermal recovery, and a significant reduction in psoriasis area and severity index, indicating that NE–QNH is a promising strategy for psoriasis therapy.
{"title":"Hyaluronic/Poloxamers-co-decorated nanoemulsion containing naringenin and quercetin for psoriasis treatment","authors":"Ryan Fauzy , Fatimah Aqilah Az Zahro , Vania Maharani , Zaizafun Faiha , Angela Bilqisth , Syaiful Choiri","doi":"10.1016/j.ijpharm.2026.126617","DOIUrl":"10.1016/j.ijpharm.2026.126617","url":null,"abstract":"<div><div>Psoriasis is a chronic autoimmune disorder characterized by persistent inflammation that progressively impairs the quality of life. Conventional corticosteroids suppress inflammatory mediators but fail to inhibit immune cell activation, leading to chronicity and long-term adverse effects. Quercetin and naringenin exhibit potent and synergistic antioxidant and anti-inflammatory properties, but their efficacy is hindered by low solubility and permeability. This study developed a quercetin–naringenin nanoemulsion hydrogel patch (NE–QNH) decorated with a hyaluronate–phospholipid complex (HA–PC) and modified with thermoresponsive polymers for targeted and controlled delivery. The nanoemulsion was optimized using a 2<sup>2</sup> factorial design based on critical quality attributes, including droplet size, polydispersity index, zeta potential, and encapsulation efficiency (EE). Hydrogel patches with varying polymer were evaluated for viscosity, drying time, spreadability, and elasticity. <em>Ex-vivo</em> permeation studies were conducted using porcine skin, and <em>in-vivo</em> efficacy was confirmed in a psoriasis model to validate the therapeutic outcome. The optimized NE–QNH exhibited a particle size of 14.94 ± 0.06 nm, a zeta potential of –9.78 ± 0.20 mV, an effective EE exceeding 80%, and high stability. The HA–PC complex decorated 87% of the nanoemulsion surface, while polymer modification formed an external matrix. <em>Ex-vivo</em> and <em>in-vivo</em> studies demonstrated a 240% increase in permeation and a 290% improvement in retention, epidermal recovery, and a significant reduction in psoriasis area and severity index, indicating that NE–QNH is a promising strategy for psoriasis therapy.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126617"},"PeriodicalIF":5.2,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044249","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}
Pub Date : 2026-02-20Epub Date: 2026-01-15DOI: 10.1016/j.ijpharm.2026.126596
Mingrui Ma , Marwa Nassar , Jason Teckoe , J. Axel Zeitler
Titanium dioxide (TiO2) is often used as a white base pigment in film coatings, but recent EU restrictions on its use in food have prompted pharmaceutical manufacturers to seek alternatives. Terahertz pulsed imaging (TPI) was used to examine the hydration of TiO2-free immediate release formulations, either without an opacifier or using calcium carbonate (CaCO3). The coatings, made from polyvinyl alcohol (PVA) or hydroxypropyl methylcellulose (HPMC), were approximately 100 µm thick. TPI results indicated that the type of film coating influenced hydration and scattering effects. However, there was no evidence that TiO2-free coatings compromised tablet disintegration. Although the HPMC coating with CaCO3 gelled upon hydration, the tablets fully hydrated within the required time. These findings offer insights into the mechanistic impacts of alternative coatings in the industry.
{"title":"Terahertz imaging of titanium dioxide-free film coating hydration and tablet core interactions","authors":"Mingrui Ma , Marwa Nassar , Jason Teckoe , J. Axel Zeitler","doi":"10.1016/j.ijpharm.2026.126596","DOIUrl":"10.1016/j.ijpharm.2026.126596","url":null,"abstract":"<div><div>Titanium dioxide (TiO<sub>2</sub>) is often used as a white base pigment in film coatings, but recent EU restrictions on its use in food have prompted pharmaceutical manufacturers to seek alternatives. Terahertz pulsed imaging (TPI) was used to examine the hydration of TiO<sub>2</sub>-free immediate release formulations, either without an opacifier or using calcium carbonate (CaCO<sub>3</sub>). The coatings, made from polyvinyl alcohol (PVA) or hydroxypropyl methylcellulose (HPMC), were approximately 100<!--> <!-->µm thick. TPI results indicated that the type of film coating influenced hydration and scattering effects. However, there was no evidence that TiO<sub>2</sub>-free coatings compromised tablet disintegration. Although the HPMC coating with CaCO<sub>3</sub> gelled upon hydration, the tablets fully hydrated within the required time. These findings offer insights into the mechanistic impacts of alternative coatings in the industry.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126596"},"PeriodicalIF":5.2,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994186","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}
Pub Date : 2026-02-20Epub Date: 2026-01-18DOI: 10.1016/j.ijpharm.2026.126598
Junhua Xu , Haochen Wang , Kaizhi Li , Shulei Pan , Gang Guo , Kaiyun Liu , Ning Wang , Lin Xiang
Oral ulcers are a common and painful condition. Current treatments, including topical corticosteroids like dexamethasone, are hindered by poor drug penetration and systemic side effects. To address these challenges, we developed a dissolving microneedle patch incorporating protease-responsive gelatin nanoparticles encapsulating dexamethasone (DEX@GNPs) for localized delivery to the oral mucosa. This system is engineered to penetrate the mucosal barrier and release dexamethasone in response to the inflammatory microenvironment, thereby enhancing drug deposition at the ulcer site. In a rat buccal ulcer model, the DEX@GNP-loaded microneedles effectively delivered dexamethasone to the target tissue layers, significantly reduced ulcer size and promoted tissue regeneration. Moreover, the responsive release of dexamethasone in the presence of elevated protease levels was associated with a marked reduction in inflammation, as evidenced by decreased levels of key pro-inflammatory cytokines. These findings indicate that DEX@GNP-loaded microneedles provide a promising approach for the localized treatment of oral ulcers and may help to improve therapeutic outcomes by enabling efficient localized corticosteroid delivery.
{"title":"Localized treatment of oral ulcers via responsive microneedle patch by enhancing mucosal penetration","authors":"Junhua Xu , Haochen Wang , Kaizhi Li , Shulei Pan , Gang Guo , Kaiyun Liu , Ning Wang , Lin Xiang","doi":"10.1016/j.ijpharm.2026.126598","DOIUrl":"10.1016/j.ijpharm.2026.126598","url":null,"abstract":"<div><div>Oral ulcers are a common and painful condition. Current treatments, including topical corticosteroids like dexamethasone, are hindered by poor drug penetration and systemic side effects. To address these challenges, we developed a dissolving microneedle patch incorporating protease-responsive gelatin nanoparticles encapsulating dexamethasone (DEX@GNPs) for localized delivery to the oral mucosa. This system is engineered to penetrate the mucosal barrier and release dexamethasone in response to the inflammatory microenvironment, thereby enhancing drug deposition at the ulcer site. In a rat buccal ulcer model, the DEX@GNP-loaded microneedles effectively delivered dexamethasone to the target tissue layers, significantly reduced ulcer size and promoted tissue regeneration. Moreover, the responsive release of dexamethasone in the presence of elevated protease levels was associated with a marked reduction in inflammation, as evidenced by decreased levels of key pro-inflammatory cytokines. These findings indicate that DEX@GNP-loaded microneedles provide a promising approach for the localized treatment of oral ulcers and may help to improve therapeutic outcomes by enabling efficient localized corticosteroid delivery.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126598"},"PeriodicalIF":5.2,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010265","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}
Pub Date : 2026-02-10Epub Date: 2025-12-21DOI: 10.1016/j.ijpharm.2025.126522
Noemí Dorival-García , Gareth Lomasney , Jonathan Bones
Cell therapies (CT) have demonstrated life-changing benefits and curative options to patients with unmet medical needs. Recent commercial successes have strengthened support for the industry; strong clinical responses are propelling additional CT products toward commercialisation. However, manufacturing of CT products continues to create challenges. Extractables and leachables (E&Ls) are a significant concern for the CT industry, which relies exclusively on single-use systems (SUSs). Investigation of the impact of SUS materials that encounter the cell-based product is a new field and the generation of more information is critical. Here, a proof-of-principle study is presented, demonstrating evidence of effects of leachates on T cells. Jurkat cells, a prototypical T cell line, were cultivated in media previously incubated in single-used bags (SUBs) utilised during incubation/expansion stages. Leachables present in the media were identified by high resolution mass spectrometry (HRAM). The physiological condition of T-cells was assessed using biological assays. Media components and metabolites were analysed over time using a direct infusion-mass spectrometry (DI-MS) method. Media containing leachables resulted in cell growth inhibition and early onset of the apoptosis/necrosis pathways. Changes in mitochondrial membrane potential suggested that leachables are cytotoxic via ΔΨm depolarisation, involving the intrinsic apoptotic pathway in the initiation of cell death. Key metabolic pathways were also significantly affected, producing accumulation of toxic metabolites and degradation of nucleic acids and lipids.
{"title":"Assessing effects of leachables in single-use systems used in cell therapy manufacture","authors":"Noemí Dorival-García , Gareth Lomasney , Jonathan Bones","doi":"10.1016/j.ijpharm.2025.126522","DOIUrl":"10.1016/j.ijpharm.2025.126522","url":null,"abstract":"<div><div>Cell therapies (CT) have demonstrated life-changing benefits and curative options to patients with unmet medical needs. Recent commercial successes have strengthened support for the industry; strong clinical responses are propelling additional CT products toward commercialisation. However, manufacturing of CT products continues to create challenges. Extractables and leachables (E&Ls) are a significant concern for the CT industry, which relies exclusively on single-use systems (SUSs). Investigation of the impact of SUS materials that encounter the cell-based product is a new field and the generation of more information is critical. Here, a proof-of-principle study is presented, demonstrating evidence of effects of leachates on T cells. Jurkat cells, a prototypical T cell line, were cultivated in media previously incubated in single-used bags (SUBs) utilised during incubation/expansion stages. Leachables present in the media were identified by high resolution mass spectrometry (HRAM). The physiological condition of T-cells was assessed using biological assays. Media components and metabolites were analysed over time using a direct infusion-mass spectrometry (DI-MS) method. Media containing leachables resulted in cell growth inhibition and early onset of the apoptosis/necrosis pathways. Changes in mitochondrial membrane potential suggested that leachables are cytotoxic via ΔΨm depolarisation, involving the intrinsic apoptotic pathway in the initiation of cell death. Key metabolic pathways were also significantly affected, producing accumulation of toxic metabolites and degradation of nucleic acids and lipids.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"690 ","pages":"Article 126522"},"PeriodicalIF":5.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145819294","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}
Pub Date : 2026-02-10Epub Date: 2026-01-07DOI: 10.1016/j.ijpharm.2026.126581
Simone Misto , Teresa Ferrillo , Sandor Balog , Fabiana Quaglia , Thomas Lee Moore
Lipid nanoparticle-borne, RNA-based therapeutics have emerged as transformative tools in nanomedicine. However, to optimize lipid nanoparticle (LNP) formulations against different pathologies, it will be necessary to change LNP payload, lipid composition, and production parameters. High-throughput formulation screening provides a way to rapidly develop and assess new LNP formulations, however this requires the capacity for high-throughput LNP physico-chemical characterization methods. When considering a shift towards automated/semi-automated high-throughput methods, it is pertinent to evaluate whether such characterization is comparable to so-called “tried and true” methods, especially in the context of scaling hit formulations from the screening phase to production. Here, we show that combining a semi-automated microfluidic system with a high-throughput characterization instrument enables the rapid production and characterization of LNP. Compared to conventional methods, the high-throughput plate reader DLS provided comparable hydrodynamic diameter data and faster analysis, albeit with lower sensitivity for RNA quantification. Additionally, we conducted an independent analysis of raw autocorrelation function data from dynamic light scattering measurements to mitigate functional differences between the high-throughput and single sample instruments. Fluorescence-based assays, also capable for high-throughput workflows, were demonstrated to be more sensitive for RNA quantification. These results illustrate that high-throughput systems can streamline LNP development, and be integrated into a translational workflow, i.e. screening to identify hit formulations, transition of hit formulations to scalable production methods, and validation of screening characterization results. This integrated workflow represents an important step for RNA therapeutic development pipelines, where increasing characterization capacity can accelerate nanomedicine development.
{"title":"Comparison and validation of a high-throughput lipid nanoparticle production and characterization workflow","authors":"Simone Misto , Teresa Ferrillo , Sandor Balog , Fabiana Quaglia , Thomas Lee Moore","doi":"10.1016/j.ijpharm.2026.126581","DOIUrl":"10.1016/j.ijpharm.2026.126581","url":null,"abstract":"<div><div>Lipid nanoparticle-borne, RNA-based therapeutics have emerged as transformative tools in nanomedicine. However, to optimize lipid nanoparticle (LNP) formulations against different pathologies, it will be necessary to change LNP payload, lipid composition, and production parameters. High-throughput formulation screening provides a way to rapidly develop and assess new LNP formulations, however this requires the capacity for high-throughput LNP physico-chemical characterization methods. When considering a shift towards automated/semi-automated high-throughput methods, it is pertinent to evaluate whether such characterization is comparable to so-called “tried and true” methods, especially in the context of scaling hit formulations from the screening phase to production. Here, we show that combining a semi-automated microfluidic system with a high-throughput characterization instrument enables the rapid production and characterization of LNP. Compared to conventional methods, the high-throughput plate reader DLS provided comparable hydrodynamic diameter data and faster analysis, albeit with lower sensitivity for RNA quantification. Additionally, we conducted an independent analysis of raw autocorrelation function data from dynamic light scattering measurements to mitigate functional differences between the high-throughput and single sample instruments. Fluorescence-based assays, also capable for high-throughput workflows, were demonstrated to be more sensitive for RNA quantification. These results illustrate that high-throughput systems can streamline LNP development, and be integrated into a translational workflow, i.e. screening to identify hit formulations, transition of hit formulations to scalable production methods, and validation of screening characterization results. This integrated workflow represents an important step for RNA therapeutic development pipelines, where increasing characterization capacity can accelerate nanomedicine development.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"690 ","pages":"Article 126581"},"PeriodicalIF":5.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145944154","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}
Pub Date : 2026-02-10Epub Date: 2025-12-31DOI: 10.1016/j.ijpharm.2025.126552
Kaixin Feng , Zhongkun Zhang , Jingjing Zhang , Xiaohan Xia , Siyu Yao , Yufei Wang , Min Wu
Doxorubicin (DOX) is limited by its clinical toxicity as a breast cancer therapy. Traditional liposomal formulations improve the tumor delivery of DOX but suffer from inadequate controlled release and low encapsulation efficiency of DOX. To address these, we developed a photo-responsive liposomal formulation DTTPL by co-encapsulating DOX and TiO2 nanostructures (TiO2) within D-α-tocopheryl succinate (α-TOS)-PEG liposomes. DTTPL successfully facilitated the release of DOX through the light-sensitive catalysis mechanism of TiO2, exhibiting 4.6 times greater cytotoxicity against MCF-7 cells compared to free DOX. Transcriptional analysis revealed synergistic DOX/DTTPL dysregulation of key genes (Brca1, Bcl-2, Bax, Caspase-3), aligning with cytotoxicity. Eventually, light-triggered DOX/DTTPL formulation resulted in 70.09% of tumor growth inhibition (TGI) in mice with no significant organ toxicity. This photo-responsive nanoformulation enables efficient controlled release of DOX, offering an alternative strategy for small molecule delivery to treat triple negative breast cancer.
{"title":"Light-responsive α-TOS liposomal nanocarriers Co-delivering TiO2 and doxorubicin for the treatment of breast cancer","authors":"Kaixin Feng , Zhongkun Zhang , Jingjing Zhang , Xiaohan Xia , Siyu Yao , Yufei Wang , Min Wu","doi":"10.1016/j.ijpharm.2025.126552","DOIUrl":"10.1016/j.ijpharm.2025.126552","url":null,"abstract":"<div><div>Doxorubicin (DOX) is limited by its clinical toxicity as a breast cancer therapy. Traditional liposomal formulations improve the tumor delivery of DOX but suffer from inadequate controlled release and low encapsulation efficiency of DOX. To address these, we developed a photo-responsive liposomal formulation DTTPL by co-encapsulating DOX and TiO<sub>2</sub> nanostructures (TiO<sub>2</sub>) within D-α-tocopheryl succinate (α-TOS)-PEG liposomes. DTTPL successfully facilitated the release of DOX through the light-sensitive catalysis mechanism of TiO<sub>2</sub>, exhibiting 4.6 times greater cytotoxicity against MCF-7 cells compared to free DOX. Transcriptional analysis revealed synergistic DOX/DTTPL dysregulation of key genes (Brca1, Bcl-2, Bax, Caspase-3), aligning with cytotoxicity.<!--> <!-->Eventually, light-triggered DOX/DTTPL formulation resulted in 70.09% of tumor growth inhibition (TGI) in mice with no significant organ toxicity. This photo-responsive nanoformulation enables efficient controlled release of DOX, offering an alternative strategy for small molecule delivery to treat triple negative breast cancer.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"690 ","pages":"Article 126552"},"PeriodicalIF":5.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892405","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}
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