Pub Date : 2026-02-20Epub 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":"2026-02-20","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 : 2026-02-20Epub Date: 2026-01-09DOI: 10.1016/j.ijpharm.2026.126565
Yahui Zhang , Liya Yu , Yehui Kang , Yuxiang Zhang , Jiaxin Li , Yu Cai , Jiajie Xu
Head and Neck Squamous Cell Carcinoma (HNSCC), characterized by a propensity for recurrence and metastasis, underscores the inadequacies of existing treatments. In this research, a liposome called DI@Lipo was developed to co-deliver cisplatin (DDP) and indocyanine green (ICG), aiming to trigger synergistic pyroptosis to enhance antitumor immunity. DI@Lipo cleverly harnessed the light-activated powers of ICG, combined them with DDP’s tumor-killing ability, to induce activation of the NLRP3 inflammasome. This, in turn, spurred gasdermin D into action, setting off a fiery pyroptosis. This chain reaction triggered a substantial release of Damage-Associated Molecular Patterns (DAMPs) and inflammatory cytokines, which in turn stimulated dendritic cells to mature and attracted an influx of killer T cells. In murine models of HNSCC, this combination therapy not only effectively eliminated primary tumors but also induced a potent abscopal effect, suppressing untreated distant tumors. Importantly, this treatment improved overall survival rates without causing notable systemic toxicity. Additionally, the DI@Lipo platform facilitated fluorescence and photoacoustic imaging (PAI) for potential treatment monitoring. These findings highlight how DI@Lipo-triggered pyroptosis could effectively transform immunologically dormant tumors into responsive ones, presenting a practical therapeutic avenue to combat treatment resistance in head and neck squamous cell carcinoma.
{"title":"Synergistic photo/chemo-therapeutic liposome induced pyroptosis and anti-tumor immunity in head and neck squamous cell carcinoma","authors":"Yahui Zhang , Liya Yu , Yehui Kang , Yuxiang Zhang , Jiaxin Li , Yu Cai , Jiajie Xu","doi":"10.1016/j.ijpharm.2026.126565","DOIUrl":"10.1016/j.ijpharm.2026.126565","url":null,"abstract":"<div><div>Head and Neck Squamous Cell Carcinoma (HNSCC), characterized by a propensity for recurrence and metastasis, underscores the inadequacies of existing treatments. In this research, a liposome called DI@Lipo was developed to co-deliver cisplatin (DDP) and indocyanine green (ICG), aiming to trigger synergistic pyroptosis to enhance antitumor immunity. DI@Lipo cleverly harnessed the light-activated powers of ICG, combined them with DDP’s tumor-killing ability, to induce activation of the NLRP3 inflammasome. This, in turn, spurred gasdermin D into action, setting off a fiery pyroptosis. This chain reaction triggered a substantial release of Damage-Associated Molecular Patterns (DAMPs) and inflammatory cytokines, which in turn stimulated dendritic cells to mature and attracted an influx of killer T cells. In murine models of HNSCC, this combination therapy not only effectively eliminated primary tumors but also induced a potent abscopal effect, suppressing untreated distant tumors. Importantly, this treatment improved overall survival rates without causing notable systemic toxicity. Additionally, the DI@Lipo platform facilitated fluorescence and photoacoustic imaging (PAI) for potential treatment monitoring. These findings highlight how DI@Lipo-triggered pyroptosis could effectively transform immunologically dormant tumors into responsive ones, presenting a practical therapeutic avenue to combat treatment resistance in head and neck squamous cell carcinoma.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126565"},"PeriodicalIF":5.2,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951952","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: 2026-01-09DOI: 10.1016/j.ijpharm.2026.126573
Chloe O. Frame , Christopher R. Iacovella , David J. Moore , Annette L. Bunge , Clare McCabe
The barrier function of the outermost layer of human skin, the stratum corneum (SC), arises from its multilamellar lipid matrix composed primarily of ceramides (CERs), cholesterol (CHOL), and free fatty acids (FFAs). Coarse-grained (CG) and atomistic molecular dynamics simulations have been used to study self-assembled multilayers comprising CERs NS, NP, AS, and AP, in pure CER systems and mixtures of CERs with CHOL and FFAs. Equilibrated CG configurations were reverse-mapped to recover atomistic details and analyzed to extract structures and hydrogen bonding. Simulations of pure CERs agreed with experimental trends: phytosphingosine CERs (NP and AP) exhibited more CO hydrogen bonds, consistent with lower amide I FTIR frequencies, than their sphingosine counterparts (NS and AS). Likewise, non-hydroxy CERs (NS and NP) exhibited more CO hydrogen bonding than their α-hydroxy analogs (AS and AP). CER mixtures with CHOL and FFA showed reduced CO hydrogen bonding compared to pure CERs, though this effect depended on water content. Hydroxyl location was critical: OH on the phytosphingosine base increased CO hydrogen bonding, whereas the α-hydroxy on the acyl chain reduced it. In CER NP:AP mixtures with CHOL and FFA, simulations reproduced the experimental repeat distances for NP-rich and AP-rich systems despite differences in hydrogen bonding. Simulations of multicomponent mixtures resembling the SC model of Bouwstra demonstrated the dominant effect of chain-length distribution, rather than CER hydrogen bonding, on permeability. This work shows how multiscale modeling integrated with experiments can uncover molecular mechanisms linking composition and SC barrier structure to interpret experimental results.
{"title":"Multiscale simulation of stratum corneum lipid mixtures: effects of ceramide headgroups on structural organization and hydrogen bonding networks","authors":"Chloe O. Frame , Christopher R. Iacovella , David J. Moore , Annette L. Bunge , Clare McCabe","doi":"10.1016/j.ijpharm.2026.126573","DOIUrl":"10.1016/j.ijpharm.2026.126573","url":null,"abstract":"<div><div>The barrier function of the outermost layer of human skin, the stratum corneum (SC), arises from its multilamellar lipid matrix composed primarily of ceramides (CERs), cholesterol (CHOL), and free fatty acids (FFAs). Coarse-grained (CG) and atomistic molecular dynamics simulations have been used to study self-assembled multilayers comprising CERs NS, NP, AS, and AP, in pure CER systems and mixtures of CERs with CHOL and FFAs. Equilibrated CG configurations were reverse-mapped to recover atomistic details and analyzed to extract structures and hydrogen bonding. Simulations of pure CERs agreed with experimental trends: phytosphingosine CERs (NP and AP) exhibited more C<img>O hydrogen bonds, consistent with lower amide I FTIR frequencies, than their sphingosine counterparts (NS and AS). Likewise, non-hydroxy CERs (NS and NP) exhibited more C<img>O hydrogen bonding than their α-hydroxy analogs (AS and AP). CER mixtures with CHOL and FFA showed reduced C<img>O hydrogen bonding compared to pure CERs, though this effect depended on water content. Hydroxyl location was critical: OH on the phytosphingosine base increased C<img>O hydrogen bonding, whereas the α-hydroxy on the acyl chain reduced it. In CER NP:AP mixtures with CHOL and FFA, simulations reproduced the experimental repeat distances for NP-rich and AP-rich systems despite differences in hydrogen bonding. Simulations of multicomponent mixtures resembling the SC model of Bouwstra demonstrated the dominant effect of chain-length distribution, rather than CER hydrogen bonding, on permeability. This work shows how multiscale modeling integrated with experiments can uncover molecular mechanisms linking composition and SC barrier structure to interpret experimental results.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126573"},"PeriodicalIF":5.2,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951982","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.2026.126602
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":"2026-02-20","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 : 2026-02-20Epub Date: 2026-01-17DOI: 10.1016/j.ijpharm.2026.126590
Hao Zhang , Shenzhi Li , Jiaxi You , Liang Yin , Di Wang , Weiwei Zheng , Qiang Yuan , Yong Jin , Xingwei Sun
Globally, hepatocellular carcinoma (HCC) is among the most prevalent malignancies and is the third most common cause of cancer-related mortality. Thermal ablation therapies for hepatocellular carcinoma, such as microwave ablation (MWA) and radiofrequency ablation (RFA) guided by imaging devices, have been widely used in clinical practice and have achieved good therapeutic efficacy but still face the difficult problems of high dependence on the experience of the operator’s puncture and damage caused by the tissue puncture. In this study, magnetothermal microspheres (MMs) loaded with Fe3O4 nanoparticles, featuring a uniform particle size (45–55 μm) and a good eddy current heating effect, were prepared from polyvinyl alcohol (PVA) via Shirasu Porous Glass (SPG) membrane emulsification. Under the action of a high-frequency alternating magnetic field (AMF), the PVA@Fe3O4 MMs could be rapidly warmed in vitro and effectively inhibited the activity of tumor cells. We successfully constructed a rabbit VX2 orthotopic liver tumor model. Under DSA guidance, the microspheres were enriched precisely in the tumor tissue, and in vivo animal experiments confirmed that the therapeutic effect of the MMs was similar to that of puncture ablation under the effect of an AMF, and further sections of important organ tissues showed good in vivo safety. Compared with traditional percutaneous ablation, microsphere-mediated magnetic thermal ablation (MTA) significantly reduces puncture trauma and is applicable to other blood-rich solid tumors, demonstrating favorable clinical prospects.
{"title":"Preparation of high-performance PVA@Fe3O4 magnetothermal microspheres for precise ablation of orthotopic hepatocellular carcinoma in a rabbit model","authors":"Hao Zhang , Shenzhi Li , Jiaxi You , Liang Yin , Di Wang , Weiwei Zheng , Qiang Yuan , Yong Jin , Xingwei Sun","doi":"10.1016/j.ijpharm.2026.126590","DOIUrl":"10.1016/j.ijpharm.2026.126590","url":null,"abstract":"<div><div>Globally, hepatocellular carcinoma (HCC) is among the most prevalent malignancies and is the third most common cause of cancer-related mortality. Thermal ablation therapies for hepatocellular carcinoma, such as microwave ablation (MWA) and radiofrequency ablation (RFA) guided by imaging devices, have been widely used in clinical practice and have achieved good therapeutic efficacy but still face the difficult problems of high dependence on the experience of the operator’s puncture and damage caused by the tissue puncture. In this study, magnetothermal microspheres (MMs) loaded with Fe<sub>3</sub>O<sub>4</sub> nanoparticles, featuring a uniform particle size (45–55 μm) and a good eddy current heating effect, were prepared from polyvinyl alcohol (PVA) via Shirasu Porous Glass (SPG) membrane emulsification. Under the action of a high-frequency alternating magnetic field (AMF), the PVA@Fe<sub>3</sub>O<sub>4</sub> MMs could be rapidly warmed in vitro and effectively inhibited the activity of tumor cells. We successfully constructed a rabbit VX2 orthotopic liver tumor model. Under DSA guidance, the microspheres were enriched precisely in the tumor tissue, and in vivo animal experiments confirmed that the therapeutic effect of the MMs was similar to that of puncture ablation under the effect of an AMF, and further sections of important organ tissues showed good in vivo safety. Compared with traditional percutaneous ablation, microsphere-mediated magnetic thermal ablation (MTA) significantly reduces puncture trauma and is applicable to other blood-rich solid tumors, demonstrating favorable clinical prospects.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126590"},"PeriodicalIF":5.2,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003620","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: 2026-01-25DOI: 10.1016/j.ijpharm.2026.126623
Aaron D. Smith , Ecaterina Bordos , Michael Devlin , Colin Hastie , Mark J. Perkins , Vaughan S. Langford , Alastair J. Florence , John Robertson
Establishing robust processing windows for pharmaceutical polymers during hot-melt extrusion (HME) remains challenging, as conventional thermal analyses reveal little about early chemical change. Here, selected-ion-flow-tube-mass-spectrometry (SIFT-MS) combined with principal component analysis (PCA) was used to characterise real-time volatile evolution under both thermogravimetric (TGA) and extrusion conditions. Centroid-distance mapping and PCA loadings revealed distinct transitions, providing a data-driven means of defining the onset of significant chemical change. Across four representative polymers (Soluplus®, Affinisol™15LV, Kollidon® VA64, and Plasdone™ S630 Ultra), each exhibited changes in volatile composition that marked the onset of temperature-driven chemical evolution. Soluplus® and Plasdone™ S630 Ultra remained stable up to ≈190 °C with optimum extrusion ranges of 150–170 °C. Kollidon® VA64 showed earlier volatile emergence near 180 °C, defining a 160–180 °C window, while Affinisol™15LV, the most viscous system, degraded above 190–200 °C, narrowing its range to 170–185 °C. A brief rheological assessment supported these chemically defined limits, confirming that changes in volatile composition coincide with softening behaviour. Overall, SIFT-MS detected subtle, low-level volatile changes that emerge well before conventional thermal indicators, enabling rapid, non-destructive definition of polymer-specific extrusion windows and enhancing process understanding in amorphous solid dispersion manufacture. Through this analysis we were able to provide a narrower processing range than those defined by their respective manufacturers.
{"title":"Process optimization in pharmaceutical hot-melt extrusion: real-time volatile detection via SIFT-MS combined with multivariate analysis","authors":"Aaron D. Smith , Ecaterina Bordos , Michael Devlin , Colin Hastie , Mark J. Perkins , Vaughan S. Langford , Alastair J. Florence , John Robertson","doi":"10.1016/j.ijpharm.2026.126623","DOIUrl":"10.1016/j.ijpharm.2026.126623","url":null,"abstract":"<div><div>Establishing robust processing windows for pharmaceutical polymers during hot-melt extrusion (HME) remains challenging, as conventional thermal analyses reveal little about early chemical change. Here, selected-ion-flow-tube-mass-spectrometry (SIFT-MS) combined with principal component analysis (PCA) was used to characterise real-time volatile evolution under both thermogravimetric (TGA) and extrusion conditions. Centroid-distance mapping and PCA loadings revealed distinct transitions, providing a data-driven means of defining the onset of significant chemical change. Across four representative polymers (<em>Soluplus®</em>, <em>Affinisol™15LV</em>, <em>Kollidon® VA64</em>, and <em>Plasdone™ S630 Ultra</em>), each exhibited changes in volatile composition that marked the onset of temperature-driven chemical evolution. <em>Soluplus®</em> and <em>Plasdone™ S630 Ultra</em> remained stable up to ≈190 °C with optimum extrusion ranges of 150–170 °C. <em>Kollidon® VA64</em> showed earlier volatile emergence near 180 °C, defining a 160–180 °C window, while <em>Affinisol™15LV</em>, the most viscous system, degraded above 190–200 °C, narrowing its range to 170–185 °C. A brief rheological assessment supported these chemically defined limits, confirming that changes in volatile composition coincide with softening behaviour. Overall, SIFT-MS detected subtle, low-level volatile changes that emerge well before conventional thermal indicators, enabling rapid, non-destructive definition of polymer-specific extrusion windows and enhancing process understanding in amorphous solid dispersion manufacture. Through this analysis we were able to provide a narrower processing range than those defined by their respective manufacturers.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126623"},"PeriodicalIF":5.2,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146063482","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.2026.126601
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":"2026-02-20","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 : 2026-02-20Epub 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":"2026-02-20","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}
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}