Hydrogels are promising wound dressings, yet traditional hydrogels often lack optimal mechanical strength and antimicrobial activity. We developed a novel sodium alginate-based metformin-loaded bentonite (Met-Ben) nanocomposite hydrogel to enhance wound healing. Metformin was encapsulated within bentonite nanoparticles via ion-exchange, achieving an entrapment efficiency of 75.6 % and a drug-loading value of 27.7 %. The nanoparticles had an average size of 364.5 nm and a zeta potential of −8.6 mV. The hydrogel exhibited an increased swelling ratio over 4 h and showed approximately 65 % degradation over 14 days. Sustained metformin release followed Korsmeyer-Peppas kinetics (n = 0.3541, indicating Fickian diffusion). ATR-FTIR and DSC confirmed the chemical integrity and amorphous state of encapsulated metformin. In vitro cytotoxicity assays confirmed its biocompatibility. In vivo, the Met-Ben hydrogel significantly accelerated wound closure (85 % at day 14), increased collagen deposition (p < 0.05, histological scoring), and enhanced fibroblast maturation, re-epithelialization, and neovascularization compared with the control. Gene expression analysis showed downregulation of TNF-α and IL-1β and upregulation of TGF-β (p < 0.01), supporting modulation of inflammation and promotion of tissue regeneration. This study introduces the first sodium alginate–bentonite–metformin nanocomposite hydrogel, offering a dual-action bioactive and structural platform for full-thickness wound healing.
{"title":"Sustained-release sodium alginate-based metformin/bentonite nanocomposite hydrogel for enhanced wound healing","authors":"Zahra Rezanejad Gatabi , Mehri Mirhoseini , Mozhgan Abasi , Mohammad Shokati Sayyad , Pedram Ebrahimnejad","doi":"10.1016/j.jddst.2026.108035","DOIUrl":"10.1016/j.jddst.2026.108035","url":null,"abstract":"<div><div>Hydrogels are promising wound dressings, yet traditional hydrogels often lack optimal mechanical strength and antimicrobial activity. We developed a novel sodium alginate-based metformin-loaded bentonite (Met-Ben) nanocomposite hydrogel to enhance wound healing. Metformin was encapsulated within bentonite nanoparticles via ion-exchange, achieving an entrapment efficiency of 75.6 % and a drug-loading value of 27.7 %. The nanoparticles had an average size of 364.5 nm and a zeta potential of −8.6 mV. The hydrogel exhibited an increased swelling ratio over 4 h and showed approximately 65 % degradation over 14 days. Sustained metformin release followed Korsmeyer-Peppas kinetics (n = 0.3541, indicating Fickian diffusion). ATR-FTIR and DSC confirmed the chemical integrity and amorphous state of encapsulated metformin. In vitro cytotoxicity assays confirmed its biocompatibility. In vivo, the Met-Ben hydrogel significantly accelerated wound closure (85 % at day 14), increased collagen deposition (p < 0.05, histological scoring), and enhanced fibroblast maturation, re-epithelialization, and neovascularization compared with the control. Gene expression analysis showed downregulation of TNF-α and IL-1β and upregulation of TGF-β (p < 0.01), supporting modulation of inflammation and promotion of tissue regeneration. This study introduces the first sodium alginate–bentonite–metformin nanocomposite hydrogel, offering a dual-action bioactive and structural platform for full-thickness wound healing.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108035"},"PeriodicalIF":4.9,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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.jddst.2026.108041
Mingjun Li , Min Zhao , Yaochen Deng , Zengming Wang , Hui Zhang , Conghui Li , Yi Cheng , Nan Liu , Shirui Mao , Aiping Zheng
Lower respiratory tract infections (LRTIs) constitute the fourth leading cause of mortality worldwide, resulting in over two million deaths annually. Bacterial pathogens are implicated in approximately 30 % of these fatalities. Dry powder inhalers (DPIs) facilitate the attainment of elevated pulmonary concentrations of antibiotics through targeted particle deposition at the site of infection, thereby optimizing local drug exposure while concurrently reducing systemic drug levels. Effective pulmonary drug delivery necessitates powders possessing optimal aerodynamic characteristics. Achieving such properties in dry powder inhalation particles is possible through diverse formulation strategies and advanced inhaler technologies. This targeted approach to drug delivery facilitates high-dose localized treatment while concurrently minimizing the potential for systemic adverse effects and the development of antibiotic resistance. This review outlines the global landscape of antibiotic DPIs, detailing marketed products and those in development. It highlights how particle-engineering and functional excipients address API constraints to enhance lung deposition. Future innovations are likely to focus on new delivery methods and strategic combinations, such as antibiotics combined with mucolytics or bacteriophages, to improve the treatment of drug-resistant respiratory infections.
{"title":"Development of antibiotic dry powder inhalers formulations for the treatment of respiratory bacterial infections: A comprehensive review","authors":"Mingjun Li , Min Zhao , Yaochen Deng , Zengming Wang , Hui Zhang , Conghui Li , Yi Cheng , Nan Liu , Shirui Mao , Aiping Zheng","doi":"10.1016/j.jddst.2026.108041","DOIUrl":"10.1016/j.jddst.2026.108041","url":null,"abstract":"<div><div>Lower respiratory tract infections (LRTIs) constitute the fourth leading cause of mortality worldwide, resulting in over two million deaths annually. Bacterial pathogens are implicated in approximately 30 % of these fatalities. Dry powder inhalers (DPIs) facilitate the attainment of elevated pulmonary concentrations of antibiotics through targeted particle deposition at the site of infection, thereby optimizing local drug exposure while concurrently reducing systemic drug levels. Effective pulmonary drug delivery necessitates powders possessing optimal aerodynamic characteristics. Achieving such properties in dry powder inhalation particles is possible through diverse formulation strategies and advanced inhaler technologies. This targeted approach to drug delivery facilitates high-dose localized treatment while concurrently minimizing the potential for systemic adverse effects and the development of antibiotic resistance. This review outlines the global landscape of antibiotic DPIs, detailing marketed products and those in development. It highlights how particle-engineering and functional excipients address API constraints to enhance lung deposition. Future innovations are likely to focus on new delivery methods and strategic combinations, such as antibiotics combined with mucolytics or bacteriophages, to improve the treatment of drug-resistant respiratory infections.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108041"},"PeriodicalIF":4.9,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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.jddst.2026.108040
Pei-Ling Liu , Jia-Lin Wang , Yi-Ying Dong , Hong Liu , Jin-Ju Lei , Bin Xu , Xin-Ru Liao , Di Han , Zi-Hao He , Si-Xue Cheng
Epidermal growth factor receptor (EGFR) targeted cancer therapy offers high selectivity and reduced toxicity. However, the therapeutic efficacy is compromised by the poor bioavailability of hydrophobic drugs such as gefitinib (GEF), and the acquired resistance. Curcumin (CUR) can sensitize tumor cells toward EGFR inhibitors and reverse drug resistance, but its application is also hindered by low solubility. To address these limitations, we developed a zein-based drug delivery system for the co-delivery of GEF and CUR. The dual-drug loaded zein-based nanoparticles (GEF/CUR@ZNP) decorated by pectin were prepared by self-assembly. GEF/CUR@ZNP exhibited a mean diameter less than 300 nm, featuring a narrow size distribution and an encapsulation efficiency higher than 80 %. The therapeutic efficacy was evaluated in vitro using PC-9 cells. Compared with free drugs, GEF/CUR@ZNP led to significantly enhanced cellular uptake, resulting in improved induction of cancer cell apoptosis and higher efficiency in downregulation of proteins promote cancer progression (e.g., Sp1, Bcl-2, VEGF, Snail, and CD44). To evaluate the efficacy of the drug delivery system in a context more relevant to clinical settings, we evaluated the EGFR inhibition efficacy by using the blood samples containing circulating tumor cells (CTCs) from non-small cell lung cancer (NSCLC) patients, and immunofluorescence labeling confirmed that GEF/CUR@ZNP achieved most effective suppression of EGFR expression. These findings demonstrate that zein-based co-delivery of GEF and CUR can overcome multiple barriers to targeted cancer therapy, and offer a clinically relevant strategy for enhancing antitumor efficacy and personalizing cancer treatment.
{"title":"Co-delivery of gefitinib and curcumin via zein-based nanoparticles to enhance EGFR signaling inhibition and prevent cancer progression","authors":"Pei-Ling Liu , Jia-Lin Wang , Yi-Ying Dong , Hong Liu , Jin-Ju Lei , Bin Xu , Xin-Ru Liao , Di Han , Zi-Hao He , Si-Xue Cheng","doi":"10.1016/j.jddst.2026.108040","DOIUrl":"10.1016/j.jddst.2026.108040","url":null,"abstract":"<div><div>Epidermal growth factor receptor (EGFR) targeted cancer therapy offers high selectivity and reduced toxicity. However, the therapeutic efficacy is compromised by the poor bioavailability of hydrophobic drugs such as gefitinib (GEF), and the acquired resistance. Curcumin (CUR) can sensitize tumor cells toward EGFR inhibitors and reverse drug resistance, but its application is also hindered by low solubility. To address these limitations, we developed a zein-based drug delivery system for the co-delivery of GEF and CUR. The dual-drug loaded zein-based nanoparticles (GEF/CUR@ZNP) decorated by pectin were prepared by self-assembly. GEF/CUR@ZNP exhibited a mean diameter less than 300 nm, featuring a narrow size distribution and an encapsulation efficiency higher than 80 %. The therapeutic efficacy was evaluated <em>in vitro</em> using PC-9 cells. Compared with free drugs, GEF/CUR@ZNP led to significantly enhanced cellular uptake, resulting in improved induction of cancer cell apoptosis and higher efficiency in downregulation of proteins promote cancer progression (e.g., Sp1, Bcl-2, VEGF, Snail, and CD44). To evaluate the efficacy of the drug delivery system in a context more relevant to clinical settings, we evaluated the EGFR inhibition efficacy by using the blood samples containing circulating tumor cells (CTCs) from non-small cell lung cancer (NSCLC) patients, and immunofluorescence labeling confirmed that GEF/CUR@ZNP achieved most effective suppression of EGFR expression. These findings demonstrate that zein-based co-delivery of GEF and CUR can overcome multiple barriers to targeted cancer therapy, and offer a clinically relevant strategy for enhancing antitumor efficacy and personalizing cancer treatment.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108040"},"PeriodicalIF":4.9,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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.jddst.2026.108039
Hongyu Zhu , Liuyang Wang , Jingyang Zhao , Zhiguo Su , Kiichi Sato , Xiaoyi Wang , Songping Zhang
All-trans retinoic acid (Ra)-mediated differentiation therapy remains the first-line treatment for acute promyelocytic leukemia (APL). However, Ra must be administered orally due to its extremely poor aqueous solubility. The absorption of Ra is influenced by various factors, which can result in variable bioavailability and, consequently, variable therapeutic effects. Accordingly, the development of a parenteral Ra formulation is highly demanded. In the current study, Choline-retinoic acid ([Cho][Ra]), which significantly improved the water solubility of Ra, was systemically evaluated as the pro-differentiation and pro-apoptosis agent for APL cells. In vitro cellular studies demonstrate that compared to Ra, [Cho][Ra] induced a more pronounced G0-G1 phase cell cycle arrest, leading to a greater inhibition of cell proliferation. Concurrently, it also promoted a higher percentage of cells to undergo differentiation. Furthermore, [Cho][Ra] showed superior efficacy in inducing late-stage apoptosis, which was associated with a more severe loss of mitochondrial membrane potential. [Cho][Ra] treatment also induced higher reactive oxygen species (ROS) levels, which suggests that ROS generation may be a key mechanistic contributor to both cell apoptosis and differentiation. These findings suggest that [Cho][Ra] could be a promising alternative to Ra, overcoming the solubility limitations and improving its efficacy in treating leukemia.
{"title":"Choline-retinoic acid ionic liquid as a potential therapy agent for acute promyelocytic leukemia","authors":"Hongyu Zhu , Liuyang Wang , Jingyang Zhao , Zhiguo Su , Kiichi Sato , Xiaoyi Wang , Songping Zhang","doi":"10.1016/j.jddst.2026.108039","DOIUrl":"10.1016/j.jddst.2026.108039","url":null,"abstract":"<div><div>All-trans retinoic acid (Ra)-mediated differentiation therapy remains the first-line treatment for acute promyelocytic leukemia (APL). However, Ra must be administered orally due to its extremely poor aqueous solubility. The absorption of Ra is influenced by various factors, which can result in variable bioavailability and, consequently, variable therapeutic effects. Accordingly, the development of a parenteral Ra formulation is highly demanded. In the current study, Choline-retinoic acid ([Cho][Ra]), which significantly improved the water solubility of Ra, was systemically evaluated as the pro-differentiation and pro-apoptosis agent for APL cells. <em>In vitro</em> cellular studies demonstrate that compared to Ra, [Cho][Ra] induced a more pronounced G0-G1 phase cell cycle arrest, leading to a greater inhibition of cell proliferation. Concurrently, it also promoted a higher percentage of cells to undergo differentiation. Furthermore, [Cho][Ra] showed superior efficacy in inducing late-stage apoptosis, which was associated with a more severe loss of mitochondrial membrane potential. [Cho][Ra] treatment also induced higher reactive oxygen species (ROS) levels, which suggests that ROS generation may be a key mechanistic contributor to both cell apoptosis and differentiation. These findings suggest that [Cho][Ra] could be a promising alternative to Ra, overcoming the solubility limitations and improving its efficacy in treating leukemia.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108039"},"PeriodicalIF":4.9,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-17DOI: 10.1016/j.jddst.2026.108028
Nejva Kaid , Gamze Camlik , Yildiz Ozsoy
Intranasal drug delivery has emerged as an effective, non-invasive strategy for targeting both systemic circulation and the central nervous system (CNS), offering a means to bypass first-pass metabolism and the blood–brain barrier (BBB). This route can significantly improve drug bioavailability and therapeutic outcomes. Among the various nanomaterials investigated for intranasal applications, carbon dots (CDs) have attracted growing interest due to their ultra-small size, tunable surface functionalization, strong photoluminescence, high aqueous solubility, chemical stability, favorable biocompatibility, and minimal cytotoxicity. These features make CDs particularly well suited for both therapeutic delivery and theranostic applications. This review provides a comprehensive overview of recent advances in CD-based intranasal delivery systems, with emphasis on their ability to enhance transport across biological barriers, improve drug stability and targeting, and support real-time imaging. Key strategies in formulation design, surface functionalization, and preclinical performance are discussed, alongside critical limitations affecting clinical translation, including incomplete mechanistic understanding, safety evaluation gaps, and challenges related to reproducibility. Together, these insights provide a framework to guide the rational design of CD-enabled intranasal systems and to inform future efforts aimed at translating preclinical advances into clinically applicable nasal drug delivery technologies.
{"title":"Carbon dots in nasal delivery: Emerging strategies for enhanced therapeutic efficacy","authors":"Nejva Kaid , Gamze Camlik , Yildiz Ozsoy","doi":"10.1016/j.jddst.2026.108028","DOIUrl":"10.1016/j.jddst.2026.108028","url":null,"abstract":"<div><div>Intranasal drug delivery has emerged as an effective, non-invasive strategy for targeting both systemic circulation and the central nervous system (CNS), offering a means to bypass first-pass metabolism and the blood–brain barrier (BBB). This route can significantly improve drug bioavailability and therapeutic outcomes. Among the various nanomaterials investigated for intranasal applications, carbon dots (CDs) have attracted growing interest due to their ultra-small size, tunable surface functionalization, strong photoluminescence, high aqueous solubility, chemical stability, favorable biocompatibility, and minimal cytotoxicity. These features make CDs particularly well suited for both therapeutic delivery and theranostic applications. This review provides a comprehensive overview of recent advances in CD-based intranasal delivery systems, with emphasis on their ability to enhance transport across biological barriers, improve drug stability and targeting, and support real-time imaging. Key strategies in formulation design, surface functionalization, and preclinical performance are discussed, alongside critical limitations affecting clinical translation, including incomplete mechanistic understanding, safety evaluation gaps, and challenges related to reproducibility. Together, these insights provide a framework to guide the rational design of CD-enabled intranasal systems and to inform future efforts aimed at translating preclinical advances into clinically applicable nasal drug delivery technologies.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108028"},"PeriodicalIF":4.9,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-17DOI: 10.1016/j.jddst.2026.108030
Pooja Sawant , Ratnesh Jain , Prajakta Dandekar
The persistent challenges of drug resistance, tumor heterogeneity, and poor predictability of traditional 2D and animal models underscore the urgent need for innovative strategies in development of safe and efficacious anti-cancer interventions. In recent years, novel drug delivery systems (NDDS) such as nanoparticles, liposomes, antibody-drug conjugates, as well as inhalable formulations have emerged as promising approaches to enhance drug targeting, efficacy, and safety, particularly in hard-to-treat malignancies like lung cancer. Concurrently, 3D in vitro tumor spheroid models have gained recognition for their ability to recapitulate key features of the tumor microenvironment, including cell-cell and cell-matrix interactions, oxygen gradients, and drug penetration barriers. This manuscript presents a comprehensive compilation of the NDDS that have been evaluated using spheroid models and demonstrated substantial therapeutic potential, with many demonstrating translational success in subsequent animal studies. By highlighting the correlation between spheroid-based screening outcomes and in vivo efficacy, we aim to highlight the importance of spheroid models as efficient, reproducible, and ethically favorable tools for early-phase drug evaluation. Overall, this review emphasizes the dual relevance of NDDS and in vitro spheroid systems in advancing precision oncology while promoting the reduction of animal usage in research.
{"title":"Emerging therapies for lung adenocarcinoma: Mechanistic and efficacy insights from spheroid-based in vitro models","authors":"Pooja Sawant , Ratnesh Jain , Prajakta Dandekar","doi":"10.1016/j.jddst.2026.108030","DOIUrl":"10.1016/j.jddst.2026.108030","url":null,"abstract":"<div><div>The persistent challenges of drug resistance, tumor heterogeneity, and poor predictability of traditional 2D and animal models underscore the urgent need for innovative strategies in development of safe and efficacious anti-cancer interventions. In recent years, novel drug delivery systems (NDDS) such as nanoparticles, liposomes, antibody-drug conjugates, as well as inhalable formulations have emerged as promising approaches to enhance drug targeting, efficacy, and safety, particularly in hard-to-treat malignancies like lung cancer. Concurrently, 3D <em>in vitro</em> tumor spheroid models have gained recognition for their ability to recapitulate key features of the tumor microenvironment, including cell-cell and cell-matrix interactions, oxygen gradients, and drug penetration barriers. This manuscript presents a comprehensive compilation of the NDDS that have been evaluated using spheroid models and demonstrated substantial therapeutic potential, with many demonstrating translational success in subsequent animal studies. By highlighting the correlation between spheroid-based screening outcomes and <em>in vivo</em> efficacy, we aim to highlight the importance of spheroid models as efficient, reproducible, and ethically favorable tools for early-phase drug evaluation. Overall, this review emphasizes the dual relevance of NDDS and <em>in vitro</em> spheroid systems in advancing precision oncology while promoting the reduction of animal usage in research.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108030"},"PeriodicalIF":4.9,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study aims to optimize the physical stability of effervescent tablets containing Physalis angulata L. fruit extract through fluid bed coating of sodium bicarbonate with various polymers and formulation optimization using a Box-Behnken design. Sodium bicarbonate was coated with 3 polymer variations, including 10 % polyethylene glycol (PEG), 0.1 % hydroxypropyl methylcellulose (HPMC), and a combination of PEG: HPMC (0.4:1) according to previous optimization studies. The coated sodium bicarbonate was then evaluated for moisture content, flow properties, morphology, Fourier-transform infrared (FT-IR) spectroscopy, and carbon dioxide (CO2) release. Compression with citric acid was conducted to assess tablet appearance and weight change. The results showed that PEG 10 % produced sodium bicarbonate powder with acceptable physical characteristics, such as moisture content, flow properties, and CO2 release. FT-IR analysis showed molecular interactions between PEG and sodium bicarbonate, showing the potential to enhance the structural integrity and stability of the coating layer. Compression of sodium bicarbonate-PEG 10 % with citric acid resulted in better visual appearance and lower weight change. In addition, Box-Behnken optimization yielded an ideal effervescent tablet formulation containing 2.83 mol acid, 7.98 mol base, and 3.55 % binder. The optimized formulation, compressed under ambient temperature and relative humidity, met physical stability criteria and showed improved flowability compared to formulations using uncoated base components.
{"title":"Optimization of effervescent tablet stability containing Physalis angulata L. fruit extract via fluid bed coating of sodium bicarbonate and Box–Behnken design","authors":"Radhia Riski , I Ketut Adnyana , Yuda Prasetya Nugraha , Heni Rachmawati","doi":"10.1016/j.jddst.2026.108032","DOIUrl":"10.1016/j.jddst.2026.108032","url":null,"abstract":"<div><div>This study aims to optimize the physical stability of effervescent tablets containing <em>Physalis angulata</em> L. fruit extract through fluid bed coating of sodium bicarbonate with various polymers and formulation optimization using a Box-Behnken design. Sodium bicarbonate was coated with 3 polymer variations, including 10 % polyethylene glycol (PEG), 0.1 % hydroxypropyl methylcellulose (HPMC), and a combination of PEG: HPMC (0.4:1) according to previous optimization studies. The coated sodium bicarbonate was then evaluated for moisture content, flow properties, morphology, Fourier-transform infrared (FT-IR) spectroscopy, and carbon dioxide (CO<sub>2</sub>) release. Compression with citric acid was conducted to assess tablet appearance and weight change. The results showed that PEG 10 % produced sodium bicarbonate powder with acceptable physical characteristics, such as moisture content, flow properties, and CO<sub>2</sub> release. FT-IR analysis showed molecular interactions between PEG and sodium bicarbonate, showing the potential to enhance the structural integrity and stability of the coating layer. Compression of sodium bicarbonate-PEG 10 % with citric acid resulted in better visual appearance and lower weight change. In addition, Box-Behnken optimization yielded an ideal effervescent tablet formulation containing 2.83 mol acid, 7.98 mol base, and 3.55 % binder. The optimized formulation, compressed under ambient temperature and relative humidity, met physical stability criteria and showed improved flowability compared to formulations using uncoated base components.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108032"},"PeriodicalIF":4.9,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-16DOI: 10.1016/j.jddst.2026.108031
Rasim Masimov , Matija Tomšič , Ellen K. Wasan
Polyelectrolyte complex nanoparticles (PECNs) are widely used as carrier systems, particularly for delivering nucleic acids and proteins. Their unique characteristics have led to extensive research into their potential as vaccine delivery platforms. Since PECNs form through electrostatic interactions, various solution and physical parameters can influence their structure during and after fabrication. We discovered that applying an electric voltage affects the physicochemical properties of PECNs comprised of chitosan complexed to a polyelectrolyte vaccine adjuvant. Subsequently, we explored the effect of voltage application on their physical properties and performance as vaccine nanocarriers. The nanoparticles were prepared using microfluidic mixing, with the physicochemical properties of these formulations assessed both before and after exposure to electric voltage. Results showed that exposure to electric voltage can alter the physicochemical properties of PECNs, subsequently impacting their in vitro efficacy. This also emphasizes the importance of carefully considering the sequential order of particle size and zeta potential determinations, as these parameters are derived from DLS and electrophoretic mobility measurements, respectively, and the latter can influence the physicochemical properties of PECNs.
{"title":"External electric field modulation of polyelectrolyte complex nanoparticles for vaccine delivery","authors":"Rasim Masimov , Matija Tomšič , Ellen K. Wasan","doi":"10.1016/j.jddst.2026.108031","DOIUrl":"10.1016/j.jddst.2026.108031","url":null,"abstract":"<div><div>Polyelectrolyte complex nanoparticles (PECNs) are widely used as carrier systems, particularly for delivering nucleic acids and proteins. Their unique characteristics have led to extensive research into their potential as vaccine delivery platforms. Since PECNs form through electrostatic interactions, various solution and physical parameters can influence their structure during and after fabrication. We discovered that applying an electric voltage affects the physicochemical properties of PECNs comprised of chitosan complexed to a polyelectrolyte vaccine adjuvant. Subsequently, we explored the effect of voltage application on their physical properties and performance as vaccine nanocarriers. The nanoparticles were prepared using microfluidic mixing, with the physicochemical properties of these formulations assessed both before and after exposure to electric voltage. Results showed that exposure to electric voltage can alter the physicochemical properties of PECNs, subsequently impacting their <em>in vitro</em> efficacy. This also emphasizes the importance of carefully considering the sequential order of particle size and zeta potential determinations, as these parameters are derived from DLS and electrophoretic mobility measurements, respectively, and the latter can influence the physicochemical properties of PECNs.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108031"},"PeriodicalIF":4.9,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-15DOI: 10.1016/j.jddst.2026.108026
Hina Tahir , Abdullah K. Alanazi , Zaheer Ahmad
Cancer continues to be a main cause of worldwide morbidity and mortality, and standard treatments encounter restrictions such as multidrug resistance, tumor heterogeneity, and systemic toxicity. These limitations have navigated the evolution of stimuli-responsive polymer-based drug delivery systems (DDSs) that increase the ratio of drug accumulation at tumor sites while decreasing systemic toxicity. Hypoxia, a primary characteristic of most solid tumors, has been determined as a significant internal stimulus for drug release. Hypoxia-responsive polymers consume oxygen-sensitive moieties such as azobenzene derivatives and nitroimidazole conjugates, which go through bioreduction under hypoxic conditions to initiate drug release. This review delivers a comparative analysis of azobenzene and nitroimidazole-based hypoxia-responsive DDS, concentrating on their synthesis, physicochemical characteristics, modes of activation, and therapeutic efficacy. Azobenzene-based systems provide dual responsiveness to hypoxia and light, while nitroimidazole-based systems depend on enzymatic bioreduction for targeted activation in deep-rooted tumors. Both systems illustrate upgraded drug selectivity, reduced toxicity, and improved therapeutic results compared to conventional DDSs. Regardless of this progress, challenges remain in accomplishing synthesis success and clinical application. Future expectations highlight hybrid and multi-targeted responsive designs, in combination with precision medicine and nanotheranostic applications. Generally, hypoxia-responsive polymeric drug delivery systems provide a potential environment for detailed, controlled, and tumor-specific drug delivery in advanced cancer treatment.
{"title":"Exploring the functional diversity of hypoxia-responsive polymers in drug delivery: A comparative analysis","authors":"Hina Tahir , Abdullah K. Alanazi , Zaheer Ahmad","doi":"10.1016/j.jddst.2026.108026","DOIUrl":"10.1016/j.jddst.2026.108026","url":null,"abstract":"<div><div>Cancer continues to be a main cause of worldwide morbidity and mortality, and standard treatments encounter restrictions such as multidrug resistance, tumor heterogeneity, and systemic toxicity. These limitations have navigated the evolution of stimuli-responsive polymer-based drug delivery systems (DDSs) that increase the ratio of drug accumulation at tumor sites while decreasing systemic toxicity. Hypoxia, a primary characteristic of most solid tumors, has been determined as a significant internal stimulus for drug release. Hypoxia-responsive polymers consume oxygen-sensitive moieties such as azobenzene derivatives and nitroimidazole conjugates, which go through bioreduction under hypoxic conditions to initiate drug release. This review delivers a comparative analysis of azobenzene and nitroimidazole-based hypoxia-responsive DDS, concentrating on their synthesis, physicochemical characteristics, modes of activation, and therapeutic efficacy. Azobenzene-based systems provide dual responsiveness to hypoxia and light, while nitroimidazole-based systems depend on enzymatic bioreduction for targeted activation in deep-rooted tumors. Both systems illustrate upgraded drug selectivity, reduced toxicity, and improved therapeutic results compared to conventional DDSs. Regardless of this progress, challenges remain in accomplishing synthesis success and clinical application. Future expectations highlight hybrid and multi-targeted responsive designs, in combination with precision medicine and nanotheranostic applications. Generally, hypoxia-responsive polymeric drug delivery systems provide a potential environment for detailed, controlled, and tumor-specific drug delivery in advanced cancer treatment.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108026"},"PeriodicalIF":4.9,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-15DOI: 10.1016/j.jddst.2026.108025
Agenor Gomes dos Santos-Neto , Helton Caio Santana Santos , Marianne Celestino Andrade , Matheus Antoni da Silva Costa , Enrik Barbosa de Almeida , Décio Fragata Silva , Ricardo Guimarães Amaral , Patrícia Severino , Juliana Cordeiro Cardoso , Margarete Zanardo Gomes , Rogério Gondak , Filipe Modolo , Ricardo Luiz Cavalcanti de Albuquerque-Júnior
Background
The therapeutic potential of tagitinin C, a potent sesquiterpene lactone from Tithonia diversifolia, is limited by its poor solubility and non-selective toxicity. This study aimed to evaluate the antitumor efficacy and safety of a tagitinin C-rich extract encapsulated in PEGylated liposomes (LPEG-ESTD), hypothesizing that this delivery system would enhance therapeutic outcomes by simultaneously activating mitochondrial apoptosis and ferroptosis pathways.
Methods
The tagitinin C-rich supercritical CO2 extract was characterized (HPLC, FTIR) and encapsulated into PEGylated liposomes via thin-film hydration. The nanoformulation was thoroughly characterized (size, zeta potential, encapsulation efficiency, release profile and structural morphology by electronic microscopy). Efficacy was evaluated through cytotoxicity on B16F10 cells and an in vivo Sarcoma 180 model. Mechanistic pathways and safety were assessed via histopathological and immunohistochemical analyses (Ki-67, TUNEL, caspase-3, Bcl-2, Bax, NF-κB, NRF2).
Results
The optimized LPEG-ESTD formulation exhibited a nanometric size (∼120 nm), high encapsulation efficiency (>90%), and sustained release. It significantly enhanced cytotoxicity in vitro and potently inhibited tumor growth in vivo. Mechanistic studies revealed the nanoformulation activated mitochondrial apoptosis (increased TUNEL, caspase-3, Bax; suppressed Ki-67 and NF-κB) and induced ferroptosis (upregulated NRF2). Crucially, the liposomal system effectively mitigated the systemic toxicity of the free extract.
Conclusion
This study demonstrates that PEGylated liposomes are a highly effective delivery system for a supercritical CO2-extracted phytotherapeutic. The LPEG-ESTD nanoformulation represents a promising strategy for cancer treatment by concurrently inducing apoptosis and ferroptosis, underscoring the value of advanced delivery systems in enhancing the efficacy and safety of natural anticancer compounds.
{"title":"PEGylated liposomal delivery of a tagitinin C-rich supercritical CO2 extract from Tithonia diversifolia induces antitumor effects via dual activation of mitochondrial apoptosis and ferroptosis","authors":"Agenor Gomes dos Santos-Neto , Helton Caio Santana Santos , Marianne Celestino Andrade , Matheus Antoni da Silva Costa , Enrik Barbosa de Almeida , Décio Fragata Silva , Ricardo Guimarães Amaral , Patrícia Severino , Juliana Cordeiro Cardoso , Margarete Zanardo Gomes , Rogério Gondak , Filipe Modolo , Ricardo Luiz Cavalcanti de Albuquerque-Júnior","doi":"10.1016/j.jddst.2026.108025","DOIUrl":"10.1016/j.jddst.2026.108025","url":null,"abstract":"<div><h3>Background</h3><div>The therapeutic potential of tagitinin C, a potent sesquiterpene lactone from <em>Tithonia diversifolia</em>, is limited by its poor solubility and non-selective toxicity. This study aimed to evaluate the antitumor efficacy and safety of a tagitinin C-rich extract encapsulated in PEGylated liposomes (LPEG-ESTD), hypothesizing that this delivery system would enhance therapeutic outcomes by simultaneously activating mitochondrial apoptosis and ferroptosis pathways.</div></div><div><h3>Methods</h3><div>The tagitinin C-rich supercritical CO<sub>2</sub> extract was characterized (HPLC, FTIR) and encapsulated into PEGylated liposomes via thin-film hydration. The nanoformulation was thoroughly characterized (size, zeta potential, encapsulation efficiency, release profile and structural morphology by electronic microscopy). Efficacy was evaluated through cytotoxicity on B16F10 cells and an <em>in vivo</em> Sarcoma 180 model. Mechanistic pathways and safety were assessed via histopathological and immunohistochemical analyses (Ki-67, TUNEL, caspase-3, Bcl-2, Bax, NF-κB, NRF2).</div></div><div><h3>Results</h3><div>The optimized LPEG-ESTD formulation exhibited a nanometric size (∼120 nm), high encapsulation efficiency (>90%), and sustained release. It significantly enhanced cytotoxicity <em>in vitro</em> and potently inhibited tumor growth <em>in vivo</em>. Mechanistic studies revealed the nanoformulation activated mitochondrial apoptosis (increased TUNEL, caspase-3, Bax; suppressed Ki-67 and NF-κB) and induced ferroptosis (upregulated NRF2). Crucially, the liposomal system effectively mitigated the systemic toxicity of the free extract.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that PEGylated liposomes are a highly effective delivery system for a supercritical CO<sub>2</sub>-extracted phytotherapeutic. The LPEG-ESTD nanoformulation represents a promising strategy for cancer treatment by concurrently inducing apoptosis and ferroptosis, underscoring the value of advanced delivery systems in enhancing the efficacy and safety of natural anticancer compounds.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108025"},"PeriodicalIF":4.9,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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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