Pub Date : 2026-01-23DOI: 10.1016/j.ijpharm.2026.126613
Paula Gonzalez-Fernandez , Luca Simula , Sébastien Jenni , Domitille Schvartz , Florina Moldovan , Olivier Jordan , Eric Allémann
Mesenchymal stem cell (MSC) therapy shows potential in regenerative medicine, particularly in treating osteoarthritis (OA). MSCs injected into the joint can secrete growth factors and extracellular matrix molecules, contributing to paracrine communication and cartilage regeneration. However, in the non-vascularized joint environment, MSCs lacking nutrient supply, starve and die too quickly to efficiently deliver enough of these factors. We have recently synthesized a new hydrogel containing hyaluronic acid and glucose (HA-GLC). This hydrogel allows MSCs to survive and proliferate in an environment with otherwise low glucose levels. Furthermore, it releases glucose through enzymatic cleavage by ß-glucosidase, an enzyme which we have shown to be available and active in human bone marrow mesenchymal stem cells (BM-MSCs). In this study, we did incorporate MSCs to this HA-GLC hydrogel. Proteomic analysis of the MSC secretome revealed that glucose deprivation modified the profile of secreted factors, inducing changes in several key pathways, including extra-cellular matrix production. We then tested the effect of glucose deprivation in MSC secretome on human chondrocyte (hCH) proliferation and IL-6 secretion. Our results showed an increase in hCH proliferation and a significant decrease in IL-6 expression, when cells were exposed to the secretome of MSCs cultured in glucose-provided media rather than glucose-deprived conditions. These findings highlighted the ability of this new technology (HA-GLC hydrogel) to modulate the MSC secretome function, potentially enhancing cartilage regeneration in OA.
{"title":"Enzymatically-responsive hyaluronan–glucose hydrogel supports MSC survival and preserves paracrine function under glucose deprivation","authors":"Paula Gonzalez-Fernandez , Luca Simula , Sébastien Jenni , Domitille Schvartz , Florina Moldovan , Olivier Jordan , Eric Allémann","doi":"10.1016/j.ijpharm.2026.126613","DOIUrl":"10.1016/j.ijpharm.2026.126613","url":null,"abstract":"<div><div>Mesenchymal stem cell (MSC) therapy shows potential in regenerative medicine, particularly in treating osteoarthritis (OA). MSCs injected into the joint can secrete growth factors and extracellular matrix molecules, contributing to paracrine communication and cartilage regeneration. However, in the non-vascularized joint environment, MSCs lacking nutrient supply, starve and die too quickly to efficiently deliver enough of these factors. We have recently synthesized a new hydrogel containing hyaluronic acid and glucose (HA-GLC). This hydrogel allows MSCs to survive and proliferate in an environment with otherwise low glucose levels. Furthermore, it releases glucose through enzymatic cleavage by ß-glucosidase, an enzyme which we have shown to be available and active in human bone marrow mesenchymal stem cells (BM-MSCs). In this study, we did incorporate MSCs to this HA-GLC hydrogel. Proteomic analysis of the MSC secretome revealed that glucose deprivation modified the profile of secreted factors, inducing changes in several key pathways, including extra-cellular matrix production. We then tested the effect of glucose deprivation in MSC secretome on human chondrocyte (hCH) proliferation and IL-6 secretion. Our results showed an increase in hCH proliferation and a significant decrease in IL-6 expression, when cells were exposed to the secretome of MSCs cultured in glucose-provided media rather than glucose-deprived conditions. These findings highlighted the ability of this new technology (HA-GLC hydrogel) to modulate the MSC secretome function, potentially enhancing cartilage regeneration in OA.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126613"},"PeriodicalIF":5.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046528","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 : 2026-01-22DOI: 10.1016/j.ijpharm.2026.126602
Mohuya Paul , Woo Jin Song , Jungkyun Im
Capsular contracture (CC) is the most frequent complication associated with silicone-based breast implant surgery and often leads to multiple revision surgeries. The implantation of a foreign object triggers the formation of a fibrous capsule around the silicone implant. Over time, excessive and uncontrollable fibrosis leads to capsule thickening and contraction, resulting in severe pain, discomfort, and implant distortion, all hallmarks of CC. Various strategies have been proposed to prevent or mitigate CC. One common strategy is surface modification of the silicone implant by introducing texture. Implant surface coating with antifibrotic and anti-inflammatory drugs is another common strategy to regulate CC. Anti-inflammatory drugs such as leukotriene inhibitor antagonists (LTRAs) and NSAIDs have demonstrated preventive effects against CC. Recently, the omega-3 polyunsaturated fatty acids (ω3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have emerged as promising candidates due to their anti-inflammatory and anti-fibrotic properties. These naturally abundant compounds have shown potential to reduce collagen deposition, thin the fibrotic capsule, and downregulate fibrosis-related inflammatory cytokines. We also discuss the molecular mechanisms by which ω3 PUFAs exert their effects and compare their advantages over conventional treatments. Overall, this narrative review outlines the current understanding of CC pathophysiology and highlights existing preventive strategies from clinical, pharmacological and biomaterial-based approaches, providing a foundation for future research on the prevention of CC.
{"title":"Multidisciplinary approaches for the prevention and management of capsular contracture: a review of clinical, pharmacological, and biomaterial-based strategies","authors":"Mohuya Paul , Woo Jin Song , Jungkyun Im","doi":"10.1016/j.ijpharm.2026.126602","DOIUrl":"10.1016/j.ijpharm.2026.126602","url":null,"abstract":"<div><div>Capsular contracture (CC) is the most frequent complication associated with silicone-based breast implant surgery and often leads to multiple revision surgeries. The implantation of a foreign object triggers the formation of a fibrous capsule around the silicone implant. Over time, excessive and uncontrollable fibrosis leads to capsule thickening and contraction, resulting in severe pain, discomfort, and implant distortion, all hallmarks of CC. Various strategies have been proposed to prevent or mitigate CC. One common strategy is surface modification of the silicone implant by introducing texture. Implant surface coating with antifibrotic and anti-inflammatory drugs is another common strategy to regulate CC. Anti-inflammatory drugs such as leukotriene inhibitor antagonists (LTRAs) and NSAIDs have demonstrated preventive effects against CC. Recently, the omega-3 polyunsaturated fatty acids (ω3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have emerged as promising candidates due to their anti-inflammatory and anti-fibrotic properties. These naturally abundant compounds have shown potential to reduce collagen deposition, thin the fibrotic capsule, and downregulate fibrosis-related inflammatory cytokines. We also discuss the molecular mechanisms by which ω3 PUFAs exert their effects and compare their advantages over conventional treatments. Overall, this narrative review outlines the current understanding of CC pathophysiology and highlights existing preventive strategies from clinical, pharmacological and biomaterial-based approaches, providing a foundation for future research on the prevention of CC.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126602"},"PeriodicalIF":5.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044255","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 : 2026-01-22DOI: 10.1016/j.ijpharm.2026.126601
Faustine Fournel , Clément Mercier , Sophie Hodin , Jérémie Pourchez
Pulmonary delivery of bronchodilators remains challenging due to dose variability and suboptimal deposition with conventional inhalers and nebulizers. Thermal aerosolization via vaping devices has emerged as a promising alternative for controlled and reproducible delivery of active pharmaceutical ingredients (APIs). This study evaluates a CE-marked medical-grade vaping device (BIKY Breathe) for pulmonary delivery of salbutamol sulfate and terbutaline sulfate, assessing aerosol performance, particle size, and transfer efficiency, with comparison to a standard pneumatic nebulizer (Cirrus™2). Aerosols were generated under standardized puffing conditions and analyzed using a Glass Twin Impinger (GTI) and a Next Generation Impactor (NGI). Four API concentrations were tested to determine respirable dose, mass median aerodynamic diameter (MMAD), and emitted-dose reproducibility. The Cirrus™2 nebulizer served as reference. The tested device produced aerosols with MMADs of 1.10 ± 0.10 µm (terbutaline) and 1.13 ± 0.14 µm (salbutamol) indicating suitability for deep-lung deposition. Average aerosol mass per puff was ∼ 6 mg for both APIs with low inter-puff variability. Terbutaline achieved a maximum transfer efficiency of ∼ 40% at 1.35–1.80 mg/mL, whereas salbutamol did not exceed 10%, likely due to physicochemical constraints. Compared with the Cirrus™2 nebulizer, the vaping device generated more efficient micron aerosols and provided higher reproducibility of respirable doses. Overall, the CE-marked device demonstrates robust and reproducible aerosolization of bronchodilators, with particle size appropriate for deep-lung delivery. Terbutaline shows strong translational potential, while salbutamol would benefit from further formulation optimization. These in vitro results support the use of medical-grade vaping devices as promising platforms for pulmonary delivery of conventional and novel APIs.
{"title":"Aerosol delivery of salbutamol and terbutaline via a CE-marked medical vaping device: aerosol characterization and transfer efficiency compared to nebulization","authors":"Faustine Fournel , Clément Mercier , Sophie Hodin , Jérémie Pourchez","doi":"10.1016/j.ijpharm.2026.126601","DOIUrl":"10.1016/j.ijpharm.2026.126601","url":null,"abstract":"<div><div>Pulmonary delivery of bronchodilators remains challenging due to dose variability and suboptimal deposition with conventional inhalers and nebulizers. Thermal aerosolization via vaping devices has emerged as a promising alternative for controlled and reproducible delivery of active pharmaceutical ingredients (APIs). This study evaluates a CE-marked medical-grade vaping device (BIKY Breathe) for pulmonary delivery of salbutamol sulfate and terbutaline sulfate, assessing aerosol performance, particle size, and transfer efficiency, with comparison to a standard pneumatic nebulizer (Cirrus™2). Aerosols were generated under standardized puffing conditions and analyzed using a Glass Twin Impinger (GTI) and a Next Generation Impactor (NGI). Four API concentrations were tested to determine respirable dose, mass median aerodynamic diameter (MMAD), and emitted-dose reproducibility. The Cirrus™2 nebulizer served as reference. The tested device produced aerosols with MMADs of 1.10 ± 0.10 µm (terbutaline) and 1.13 ± 0.14 µm (salbutamol) indicating suitability for deep-lung deposition. Average aerosol mass per puff was ∼ 6 mg for both APIs with low inter-puff variability. Terbutaline achieved a maximum transfer efficiency of ∼ 40% at 1.35–1.80 mg/mL, whereas salbutamol did not exceed 10%, likely due to physicochemical constraints. Compared with the Cirrus™2 nebulizer, the vaping device generated more efficient micron aerosols and provided higher reproducibility of respirable doses. Overall, the CE-marked device demonstrates robust and reproducible aerosolization of bronchodilators, with particle size appropriate for deep-lung delivery. Terbutaline shows strong translational potential, while salbutamol would benefit from further formulation optimization. These <em>in vitro</em> results support the use of medical-grade vaping devices as promising platforms for pulmonary delivery of conventional and novel APIs.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126601"},"PeriodicalIF":5.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044310","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 : 2026-01-22DOI: 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":"2026-01-22","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}
Infected wounds present significant clinical challenges due to persistent bacterial infection, prolonged inflammation, impaired angiogenesis, and tenacious biofilm formation, which collectively hinder the healing process. Conventional monotherapies often fail to address these intertwined pathological factors effectively. In this study, we developed a novel hot spring-inspired microneedle (MN) patch for co-delivery of inactivated Akkermansia muciniphila (Akk), copper sulfide nanoparticles (CuS NPs), and arginine (Arg) to promote healing of infected wounds. The MN system not only penetrates biofilms physically but also delivers therapeutic agents efficiently into the wound bed. Under near-infrared laser irradiation, CuS NPs generate mild photothermal heating, mimicking the thermal component of hot spring therapy. Importantly, we discovered that Arg facilitates the degradation of CuS NPs, leading to sustained release of Cu2+ ions. This process combines mild photothermia with copper ion release to emulate a "hot spring-like" ion bath, providing synergistic antibacterial and pro-angiogenic effects. Meanwhile, inactivated Akk contributes to immunomodulation by polarizing macrophages toward an anti-inflammatory phenotype, thereby alleviating chronic inflammation. Together, these components work cooperatively through photothermal therapy, antibacterial action, angiogenesis promotion, and anti-inflammatory modulation, resulting in accelerated wound closure in an infected mouse model. This multifunctional MN platform represents a promising therapeutic strategy for managing chronic infected wounds.
{"title":"\"Hot spring\"-mimetic microneedle patches delivering probiotics to accelerate infected wound healing via antibacterial, anti-inflammatory, and angiogenesis.","authors":"Guoyun Wan, Lina Dou, Ruiling Gou, Jiale Xu, Xiaodong Liang, Dan Wang, Tian Li, Yaojia Li, Wenbin Nan, Jiaqi Qin, Xianwen Wang, Hongli Chen, Haijiao Wang","doi":"10.1016/j.ijpharm.2026.126615","DOIUrl":"10.1016/j.ijpharm.2026.126615","url":null,"abstract":"<p><p>Infected wounds present significant clinical challenges due to persistent bacterial infection, prolonged inflammation, impaired angiogenesis, and tenacious biofilm formation, which collectively hinder the healing process. Conventional monotherapies often fail to address these intertwined pathological factors effectively. In this study, we developed a novel hot spring-inspired microneedle (MN) patch for co-delivery of inactivated Akkermansia muciniphila (Akk), copper sulfide nanoparticles (CuS NPs), and arginine (Arg) to promote healing of infected wounds. The MN system not only penetrates biofilms physically but also delivers therapeutic agents efficiently into the wound bed. Under near-infrared laser irradiation, CuS NPs generate mild photothermal heating, mimicking the thermal component of hot spring therapy. Importantly, we discovered that Arg facilitates the degradation of CuS NPs, leading to sustained release of Cu<sup>2+</sup> ions. This process combines mild photothermia with copper ion release to emulate a \"hot spring-like\" ion bath, providing synergistic antibacterial and pro-angiogenic effects. Meanwhile, inactivated Akk contributes to immunomodulation by polarizing macrophages toward an anti-inflammatory phenotype, thereby alleviating chronic inflammation. Together, these components work cooperatively through photothermal therapy, antibacterial action, angiogenesis promotion, and anti-inflammatory modulation, resulting in accelerated wound closure in an infected mouse model. This multifunctional MN platform represents a promising therapeutic strategy for managing chronic infected wounds.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126615"},"PeriodicalIF":5.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040511","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 : 2026-01-21DOI: 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":"2026-01-21","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}
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":"2026-01-20","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 : 2026-01-19DOI: 10.1016/j.ijpharm.2026.126594
Dan Hawthorne , Cheng-Chun Peng , Emma Ward , Susan Sandeman , Ananth SV Pannala , Dharmendra Jani , Inna Maltseva , Andrew W Lloyd
Topical delivery of osmoprotectants to ocular surface has been shown to be a promising solution to ocular discomfort thought to be associated with corneal hyperosmolarity. Currently, most osmoprotectants are administrated by aqueous eyedrops, which are associated with poor bioavailability and short residence time in the tear film, requiring repeated dosing to maintain the osmoprotectant concentration above the effective level. In response to this challenge, this work describes poly(vinyl glycine betaine) (PV-GB), a degradable ester quat polymer which gradually releases the osmoprotectant, glycine betaine (GB), over a period of days to weeks, with release rate strongly dependent on pH of its surroundings. PV-GB was embedded into commercial contact lenses (CLs) alongside a polyanion, hyaluronic acid (HA), to provide extended release of GB during a period reflecting the typical usage of a daily disposable CL wear of 8 – 16 h. A GB release lifetime of ≪48 hrs was achieved from a system comprising PV-GB/HA embedded within an anionic CL using a simple soaking method. Further experiments indicated the polymer was stable to autoclave sterilisation, had a shelf-life of 6 + months (under optimised solution conditions), and was likely to be mucoadhesive, which would be expected to enhance bioavailability of GB at the ocular surface.
{"title":"A contact lens-embedded betaine ester polymer for pH-responsive release of an osmoprotectant to the corneal surface","authors":"Dan Hawthorne , Cheng-Chun Peng , Emma Ward , Susan Sandeman , Ananth SV Pannala , Dharmendra Jani , Inna Maltseva , Andrew W Lloyd","doi":"10.1016/j.ijpharm.2026.126594","DOIUrl":"10.1016/j.ijpharm.2026.126594","url":null,"abstract":"<div><div>Topical delivery of osmoprotectants to ocular surface has been shown to be a promising solution to ocular discomfort thought to be associated with corneal hyperosmolarity. Currently, most osmoprotectants are administrated by aqueous eyedrops, which are associated with poor bioavailability and short residence time in the tear film, requiring repeated dosing to maintain the osmoprotectant concentration above the effective level. In response to this challenge, this work describes poly(vinyl glycine betaine) (PV-GB), a degradable ester quat polymer which gradually releases the osmoprotectant, glycine betaine (GB), over a period of days to weeks, with release rate strongly dependent on pH of its surroundings. PV-GB was embedded into commercial contact lenses (CLs) alongside a polyanion, hyaluronic acid (HA), to provide extended release of GB during a period reflecting the typical usage of a daily disposable CL wear of 8 – 16 h. A GB release lifetime of ≪48 hrs was achieved from a system comprising PV-GB/HA embedded within an anionic CL using a simple soaking method. Further experiments indicated the polymer was stable to autoclave sterilisation, had a shelf-life of 6 + months (under optimised solution conditions), and was likely to be mucoadhesive, which would be expected to enhance bioavailability of GB at the ocular surface.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126594"},"PeriodicalIF":5.2,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018532","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 : 2026-01-18DOI: 10.1016/j.ijpharm.2026.126595
Yuzhe Wang , Lu Sheng , Lin Bu , Huijuan Li , Jianxin Wu , Qing Huang
Phospholipid vesicle-based permeation assay (PVPA) is widely applied as in vitro skin alternative model by mimicking stratum corneum to evaluate the transdermal application of drugs and chemicals. However, it is composed of lipid components only, which suffer from limitations of achieving accurate permeability prediction. To remedy this shortcoming, inactive immortalized human keratinocytes (HaCaT) were integrated as component to construct epidermal-mimicking model: EpiPVPA. The EpiPVPA could tolerate the pH 3–10 as well as up to 30% ethanol and was stable for 2 weeks at 4 ℃. And the permeation evaluation by Franz diffusion test of 14 drugs demonstrated that EpiPVPA model is comparable to porcine skin with strong correlation. After quantitative structure–property relationship (QSPR) analysis of physicochemical descriptors of 14 drugs, HLB, TPSA, and log P were selected as main factors applied to build multiple linear regression (MLR) equation, and the corresponding linear correlation R2 was elevated to 0.9010. EpiPVPA model is feasible to be applied to permeation evaluation of drugs and cosmetics.
{"title":"A novel epidermal mimicking phospholipid vesicle-based permeation assay: EpiPVPA for in vitro permeation evaluation","authors":"Yuzhe Wang , Lu Sheng , Lin Bu , Huijuan Li , Jianxin Wu , Qing Huang","doi":"10.1016/j.ijpharm.2026.126595","DOIUrl":"10.1016/j.ijpharm.2026.126595","url":null,"abstract":"<div><div>Phospholipid vesicle-based permeation assay (PVPA) is widely applied as <em>in vitro</em> skin alternative model by mimicking stratum corneum to evaluate the transdermal application of drugs and chemicals. However, it is composed of lipid components only, which suffer from limitations of achieving accurate permeability prediction. To remedy this shortcoming, inactive immortalized human keratinocytes (HaCaT) were integrated as component to construct epidermal-mimicking model: EpiPVPA. The EpiPVPA could tolerate the pH 3–10 as well as up to 30% ethanol and was stable for 2 weeks at 4 ℃. And the permeation evaluation by Franz diffusion test of 14 drugs demonstrated that EpiPVPA model is comparable to porcine skin with strong correlation. After quantitative structure–property relationship (QSPR) analysis of physicochemical descriptors of 14 drugs, HLB, TPSA, and log P were selected as main factors applied to build multiple linear regression (MLR) equation, and the corresponding linear correlation R<sup>2</sup> was elevated to 0.9010. EpiPVPA model is feasible to be applied to permeation evaluation of drugs and cosmetics.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126595"},"PeriodicalIF":5.2,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010282","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 : 2026-01-18DOI: 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":"2026-01-18","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}
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