Pub Date : 2026-01-27DOI: 10.1016/j.ijpharm.2026.126630
Kosuke Wakayama, Sho Kurihara, Yuta Kurashina
Intranasal administration offers a minimally invasive route for drug delivery to the brain by bypassing the blood-brain barrier compared to conventional intravenous and intrathecal administration. However, conventional intranasal delivery devices have difficulty accessing the entire olfactory epithelium region. This is because the olfactory epithelium is located deep in the upper nasal cavity. Therefore, the development of an atomization device capable of delivering aerosols across the whole olfactory epithelium is required to achieve direct access to the brain. Here, we propose an olfactory epithelium-targeted intranasal atomization system based on a narrow-width surface acoustic wave (NWSAW) device with directional atomization to the olfactory epithelium region. The NWSAW device with a width of 5 mm was fabricated for insertion through the external nostril. Compared with a nasal spray, the NWSAW device produced narrower atomization angles and smaller particles. Also, the NWSAW device with the longest busbar and the narrowest aperture width (LBNA) achieved atomization at lower input power. Moreover, an extended LBNA (Ex-LBNA) enabled deeper nasal insertion. Therefore, Ex-LBNA achieved atomization across the entire olfactory epithelium region, unlike the nasal spray and the LBNA. Notably, the immunoreactivity of insulin, a biopharmaceutical, was largely retained after the atomization process with the NWSAW device. These results indicate the potential of directional atomization using the NWSAW device for drug delivery to the brain.
{"title":"Narrow-width surface acoustic wave device-driven olfactory epithelium-targeted intranasal atomization.","authors":"Kosuke Wakayama, Sho Kurihara, Yuta Kurashina","doi":"10.1016/j.ijpharm.2026.126630","DOIUrl":"10.1016/j.ijpharm.2026.126630","url":null,"abstract":"<p><p>Intranasal administration offers a minimally invasive route for drug delivery to the brain by bypassing the blood-brain barrier compared to conventional intravenous and intrathecal administration. However, conventional intranasal delivery devices have difficulty accessing the entire olfactory epithelium region. This is because the olfactory epithelium is located deep in the upper nasal cavity. Therefore, the development of an atomization device capable of delivering aerosols across the whole olfactory epithelium is required to achieve direct access to the brain. Here, we propose an olfactory epithelium-targeted intranasal atomization system based on a narrow-width surface acoustic wave (NWSAW) device with directional atomization to the olfactory epithelium region. The NWSAW device with a width of 5 mm was fabricated for insertion through the external nostril. Compared with a nasal spray, the NWSAW device produced narrower atomization angles and smaller particles. Also, the NWSAW device with the longest busbar and the narrowest aperture width (LBNA) achieved atomization at lower input power. Moreover, an extended LBNA (Ex-LBNA) enabled deeper nasal insertion. Therefore, Ex-LBNA achieved atomization across the entire olfactory epithelium region, unlike the nasal spray and the LBNA. Notably, the immunoreactivity of insulin, a biopharmaceutical, was largely retained after the atomization process with the NWSAW device. These results indicate the potential of directional atomization using the NWSAW device for drug delivery to the brain.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126630"},"PeriodicalIF":5.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146085556","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 : 2026-01-27DOI: 10.1016/j.ijpharm.2026.126627
Qin Nie , Jiahe Liu , Ying Cui , Feng Li , Mubarak G. Bello , Jialong Wang , Shiyu Zheng , Shuang Shao , Li Wu , Caifen Wang , Lixin Sun , Jiwen Zhang
Dexamethasone (DEX), a potent glucocorticoid with anti-inflammatory and immunosuppressive properties, exhibits dose-limiting systemic toxicity during long-term use. Inhalation therapy enables targeted pulmonary delivery, enhancing therapeutic efficacy while minimizing systemic exposure compared to oral routes. This study designed a DEX dry powder inhaler (DPI) formulation exhibiting excellent aerodynamic performance with a good fine particle fraction (FPF = 49.01%), which achieved approximately 7.1-fold higher pulmonary exposure relative to intravenous injection at an equivalent dose. Additionally, a 10-fold dose reduction of DEX achieved equivalent efficacy to the i.v. DEX group and significantly alleviated acute lung injury (ALI). The elevation ratios of lung coefficient in the intragastric administration of DEX raw material solution (i.g. DEX) group at 7, 14, and 28 days were approximately 4.0-, 2.1-, and 5.8-fold higher than those of in the inhalation of low-dose DEX DPI formulation (inhal. L-DEX) group in tolerability evaluation, indicating the less severe pulmonary edema in the inhalation group. Notably, a 10-fold lower DEX dose administered via inhalation reduced significantly systemic and pulmonary toxicity by organ and blood indicators at 7, 14 and 28 days, compared to high-dose intragastric administration (p < 0.01). Overall, this optimized pulmonary DEX delivery strategy demonstrated significant potential for clinical translation, offering enhanced lung targeting, efficacy at reduced doses, and a favorable safety profile.
{"title":"Pulmonary delivery of low-dose dexamethasone significantly reduces toxicity in acute lung injury therapy","authors":"Qin Nie , Jiahe Liu , Ying Cui , Feng Li , Mubarak G. Bello , Jialong Wang , Shiyu Zheng , Shuang Shao , Li Wu , Caifen Wang , Lixin Sun , Jiwen Zhang","doi":"10.1016/j.ijpharm.2026.126627","DOIUrl":"10.1016/j.ijpharm.2026.126627","url":null,"abstract":"<div><div>Dexamethasone (DEX), a potent glucocorticoid with anti-inflammatory and immunosuppressive properties, exhibits dose-limiting systemic toxicity during long-term use. Inhalation therapy enables targeted pulmonary delivery, enhancing therapeutic efficacy while minimizing systemic exposure compared to oral routes. This study designed a DEX dry powder inhaler (DPI) formulation exhibiting excellent aerodynamic performance with a good fine particle fraction (FPF = 49.01%), which achieved approximately 7.1-fold higher pulmonary exposure relative to intravenous injection at an equivalent dose. Additionally, a 10-fold dose reduction of DEX achieved equivalent efficacy to the i.v. DEX group and significantly alleviated acute lung injury (ALI). The elevation ratios of lung coefficient in the intragastric administration of DEX raw material solution (i.g. DEX) group at 7, 14, and 28 days were approximately 4.0-, 2.1-, and 5.8-fold higher than those of in the inhalation of low-dose DEX DPI formulation (inhal. L-DEX) group in tolerability evaluation, indicating the less severe pulmonary edema in the inhalation group. Notably, a 10-fold lower DEX dose administered via inhalation reduced significantly systemic and pulmonary toxicity by organ and blood indicators at 7, 14 and 28 days, compared to high-dose intragastric administration (<em>p < 0.01</em>). Overall, this optimized pulmonary DEX delivery strategy demonstrated significant potential for clinical translation, offering enhanced lung targeting, efficacy at reduced doses, and a favorable safety profile.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"692 ","pages":"Article 126627"},"PeriodicalIF":5.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146085512","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}
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss, α-synuclein aggregation, mitochondrial dysfunction, and persistent neuroinflammation. Despite symptomatic advances, the blood-brain barrier (BBB) continues to restrict the delivery of many potentially disease-modifying agents. Intranasal (IN) administration, by exploiting direct olfactory and trigeminal pathways, offers a non-invasive means to bypass the BBB. When combined with lipid-based nanoparticles (LNPs), this route has shown promise in enhancing central nervous system targeting, drug protection, and controlled release. This review examines the preclinical landscape of LNP-enabled IN delivery for PD, highlighting applications across dopamine replacement, anti-aggregatory strategies, antioxidant and anti-inflammatory therapies, and neurotrophic or gene-based interventions. In animal models, IN-LNP systems have achieved significant increases in brain uptake compared to free drug, with associated improvements in behavioral metrics such as motor coordination and dopaminergic neuron survival. However, these encouraging findings are drawn almost exclusively from rodent studies; no clinical trials have yet evaluated IN-LNP platforms in human PD. Major translational challenges persist, including interspecies anatomical differences, limited long-term safety data, formulation variability, and regulatory complexity. As such, while IN-LNP strategies represent a promising and versatile approach, their clinical potential is contingent on rigorous future validation.
{"title":"Unlocking the potential of lipid-based nanoparticles for intranasal drug delivery in Parkinson's disease.","authors":"Yonas Degelo Geremamo, Anwarul Hasan, Shaikh Abdur Razzak, Shihab Uddin","doi":"10.1016/j.ijpharm.2026.126604","DOIUrl":"10.1016/j.ijpharm.2026.126604","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss, α-synuclein aggregation, mitochondrial dysfunction, and persistent neuroinflammation. Despite symptomatic advances, the blood-brain barrier (BBB) continues to restrict the delivery of many potentially disease-modifying agents. Intranasal (IN) administration, by exploiting direct olfactory and trigeminal pathways, offers a non-invasive means to bypass the BBB. When combined with lipid-based nanoparticles (LNPs), this route has shown promise in enhancing central nervous system targeting, drug protection, and controlled release. This review examines the preclinical landscape of LNP-enabled IN delivery for PD, highlighting applications across dopamine replacement, anti-aggregatory strategies, antioxidant and anti-inflammatory therapies, and neurotrophic or gene-based interventions. In animal models, IN-LNP systems have achieved significant increases in brain uptake compared to free drug, with associated improvements in behavioral metrics such as motor coordination and dopaminergic neuron survival. However, these encouraging findings are drawn almost exclusively from rodent studies; no clinical trials have yet evaluated IN-LNP platforms in human PD. Major translational challenges persist, including interspecies anatomical differences, limited long-term safety data, formulation variability, and regulatory complexity. As such, while IN-LNP strategies represent a promising and versatile approach, their clinical potential is contingent on rigorous future validation.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126604"},"PeriodicalIF":5.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146085633","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":"2026-01-27","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 : 2026-01-26DOI: 10.1016/j.ijpharm.2026.126619
Xuerui Ma, Jiajia Jia, Jiajie Chen, Xiaoqi An, Tingting Chen, Ji Li, Dongkai Wang
Cetirizine eye drops provide rapid symptom relief in allergic conjunctivitis but are limited by short precorneal residence and frequent dosing. This study aimed to develop and compare dual pH- and temperature-responsive in situ gels incorporating Poloxamer and two Carbopol grades to enhance ocular retention and improve therapeutic efficacy. Two formulations were prepared using Poloxamer 407/188 with either Carbopol AA-1 (AA-Gel) or Carbopol TR-1(TR-Gel). Sol–gel transition, microstructure, rheology, erosion, drug release, irritation, precorneal retention, and pharmacodynamic performance were evaluated. The two Carbopol grades generated distinct gel networks, with the TR- Gel forming thicker structural struts, exhibiting higher viscosity, greater resistance to dilution, slower erosion, prolonged precorneal retention, and more sustained cetirizine release. In vivo, the TR-Gel reduced scratching behavior, inflammatory cytokines, and histopathological damage compared to both the AA-Gel and commercial eye drops, without causing ocular irritation. The dual-responsive behavior and Carbopol-dependent network architecture enhanced the stability, retention, and pharmacodynamic performance of cetirizine in situ gels. The TR-Gel, in particular, shows promise as a patient-friendly and more effective alternative to conventional eye drops for managing allergic conjunctivitis.
{"title":"Temperature- and pH-responsive cetirizine hydrochloride in situ gels for enhanced ocular delivery in allergic conjunctivitis","authors":"Xuerui Ma, Jiajia Jia, Jiajie Chen, Xiaoqi An, Tingting Chen, Ji Li, Dongkai Wang","doi":"10.1016/j.ijpharm.2026.126619","DOIUrl":"10.1016/j.ijpharm.2026.126619","url":null,"abstract":"<div><div>Cetirizine eye drops provide rapid symptom relief in allergic conjunctivitis but are limited by short precorneal residence and frequent dosing. This study aimed to develop and compare dual pH- and temperature-responsive in situ gels incorporating Poloxamer and two Carbopol grades to enhance ocular retention and improve therapeutic efficacy. Two formulations were prepared using Poloxamer 407/188 with either Carbopol AA-1 (AA-Gel) or Carbopol TR-1(TR-Gel). Sol–gel transition, microstructure, rheology, erosion, drug release, irritation, precorneal retention, and pharmacodynamic performance were evaluated. The two Carbopol grades generated distinct gel networks, with the TR- Gel forming thicker structural struts, exhibiting higher viscosity, greater resistance to dilution, slower erosion, prolonged precorneal retention, and more sustained cetirizine release. <em>In vivo</em>, the TR-Gel reduced scratching behavior, inflammatory cytokines, and histopathological damage compared to both the AA-Gel and commercial eye drops, without causing ocular irritation. The dual-responsive behavior and Carbopol-dependent network architecture enhanced the stability, retention, and pharmacodynamic performance of cetirizine in situ gels. The TR-Gel, in particular, shows promise as a patient-friendly and more effective alternative to conventional eye drops for managing allergic conjunctivitis.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126619"},"PeriodicalIF":5.2,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075210","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 : 2026-01-25DOI: 10.1016/j.ijpharm.2026.126624
Améline Delanne-Cumémal, Vincent Verney, Stéphane Portanguen, Khaled Fadhlaoui, Sandrine Chalancon, Ghislain Garrait, Eric Beyssac, Emmanuelle Lainé
The potential of Adansonia digitata (baobab) pulp polysaccharides (BB), combined with whey protein (WP) and alginate (ALG), was evaluated as a novel pharmaceutical excipient to enhance the viscosity, swelling behavior, controlled release, and mucoadhesive properties of hydrogels prepared by the ionotropic gelation technique. Hydrogels based on BB, WP, and ALG, alone or in combinations (WP/BB, WP/ALG, ALG/BB, and WP/ALG/BB), were characterized by infrared spectroscopy and zeta potential measurements. Rheological, swelling, controlled release, and mucoadhesion studies were conducted to assess the functional contribution of BB and its synergistic effects with WP and ALG. All polymers exhibited viscoelastic solid behavior (G' > G″). For each polymer, with or without crosslinking, molecular interactions were observed, leading to variations in the Tan δ parameter. The crosslinked WP/ALG/BB hydrogel exhibited reduced polymer swelling and provided a more sustained release of the incorporated active substance. In vitro and ex vivo studies demonstrated strong interactions between the polymeric matrices and intestinal mucus, with the WP/ALG/BB system showing the highest mucoadhesion. Further in vivo investigations are needed to confirm the ability of BB to enhance the oral bioavailability of active substances. Overall, Adansonia digitata pulp polysaccharides, in combination with whey protein and alginate, represent a promising natural excipient for the development of bioadhesive hydrogels and cold-gelled delivery systems in pharmaceutical formulations.
{"title":"Polysaccharides from Adansonia digitata combined with whey protein and alginate enhance the viscosity, swelling, controlled release, and mucoadhesion properties of hydrogels for oral drug delivery.","authors":"Améline Delanne-Cumémal, Vincent Verney, Stéphane Portanguen, Khaled Fadhlaoui, Sandrine Chalancon, Ghislain Garrait, Eric Beyssac, Emmanuelle Lainé","doi":"10.1016/j.ijpharm.2026.126624","DOIUrl":"10.1016/j.ijpharm.2026.126624","url":null,"abstract":"<p><p>The potential of Adansonia digitata (baobab) pulp polysaccharides (BB), combined with whey protein (WP) and alginate (ALG), was evaluated as a novel pharmaceutical excipient to enhance the viscosity, swelling behavior, controlled release, and mucoadhesive properties of hydrogels prepared by the ionotropic gelation technique. Hydrogels based on BB, WP, and ALG, alone or in combinations (WP/BB, WP/ALG, ALG/BB, and WP/ALG/BB), were characterized by infrared spectroscopy and zeta potential measurements. Rheological, swelling, controlled release, and mucoadhesion studies were conducted to assess the functional contribution of BB and its synergistic effects with WP and ALG. All polymers exhibited viscoelastic solid behavior (G' > G″). For each polymer, with or without crosslinking, molecular interactions were observed, leading to variations in the Tan δ parameter. The crosslinked WP/ALG/BB hydrogel exhibited reduced polymer swelling and provided a more sustained release of the incorporated active substance. In vitro and ex vivo studies demonstrated strong interactions between the polymeric matrices and intestinal mucus, with the WP/ALG/BB system showing the highest mucoadhesion. Further in vivo investigations are needed to confirm the ability of BB to enhance the oral bioavailability of active substances. Overall, Adansonia digitata pulp polysaccharides, in combination with whey protein and alginate, represent a promising natural excipient for the development of bioadhesive hydrogels and cold-gelled delivery systems in pharmaceutical formulations.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126624"},"PeriodicalIF":5.2,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146063460","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 : 2026-01-23DOI: 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}
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