Pub Date : 2025-02-18DOI: 10.1016/j.jddst.2025.106728
Çiğdem Kip , Esin Akbay Çetin , Burcu Gökçal Kapucu , Razan Anwar Hamdan , Mustafa Polat , Mehmet Ali Onur , Ali Tuncel
For the first time, ultrafine Pd nanoparticles (Pd NPs), 8.7 nm in size, were synthesized using the ‘universal viscosity-mediated assembly strategy’ (UVMAS). An aqueous dispersion containing ultrafine, well-dispersed nanoparticles with a mode hydrodynamic size of 10.1 nm was obtained without any significant agglomeration. Pd NPs synthesized with UVMAS contained Pd (0) (57.2 %) and PdO (42.8 %) phases. A self-propelled motion of Pd NPs was observed, attributed to the generation of O2 bubbles through the decomposition of H2O2 by their strong catalase (CAT)-like activity. Pd NPs also exhibited peroxidase (POD)-like activity. Toxic hydroxyl (●OH) and superoxide anion (O2−●) radical generation with Pd NPs was demonstrated by ESR spectroscopy. Their glutathione (GSH) depletion ability was explained by chemisorption of GSH onto Pd NPs via thiol functionality. Pd NPs also exhibited an excellent NIR light absorption, which in turn a photothermal conversion ability with a photothermal conversion efficiency of 43.2 % and a band gap energy of 1.5 eV. The usability of Pd NPs as a promising nanozyme with photothermal and chemodynamic functions was exemplified by the interaction with T98G glioblastoma cells under in-vitro conditions. In-vitro cell deaths up to 85 % were achieved by simultaneous use of photothermal and chemodynamic modalities.
{"title":"Ultrafine palladium based nanozyme exhibiting photothermal and chemodynamic responses with O2 bubble driven motion and glutathione depletion ability","authors":"Çiğdem Kip , Esin Akbay Çetin , Burcu Gökçal Kapucu , Razan Anwar Hamdan , Mustafa Polat , Mehmet Ali Onur , Ali Tuncel","doi":"10.1016/j.jddst.2025.106728","DOIUrl":"10.1016/j.jddst.2025.106728","url":null,"abstract":"<div><div>For the first time, ultrafine Pd nanoparticles (Pd NPs), 8.7 nm in size, were synthesized using the ‘universal viscosity-mediated assembly strategy’ (UVMAS). An aqueous dispersion containing ultrafine, well-dispersed nanoparticles with a mode hydrodynamic size of 10.1 nm was obtained without any significant agglomeration. Pd NPs synthesized with UVMAS contained Pd (0) (57.2 %) and PdO (42.8 %) phases. A self-propelled motion of Pd NPs was observed, attributed to the generation of O<sub>2</sub> bubbles through the decomposition of H<sub>2</sub>O<sub>2</sub> by their strong catalase (CAT)-like activity. Pd NPs also exhibited peroxidase (POD)-like activity. Toxic hydroxyl (●OH) and superoxide anion (O<sub>2</sub><sup>−●</sup>) radical generation with Pd NPs was demonstrated by ESR spectroscopy. Their glutathione (GSH) depletion ability was explained by chemisorption of GSH onto Pd NPs via thiol functionality. Pd NPs also exhibited an excellent NIR light absorption, which in turn a photothermal conversion ability with a photothermal conversion efficiency of 43.2 % and a band gap energy of 1.5 eV. The usability of Pd NPs as a promising nanozyme with photothermal and chemodynamic functions was exemplified by the interaction with T98G glioblastoma cells under <em>in-vitro</em> conditions. <em>In-vitro</em> cell deaths up to 85 % were achieved by simultaneous use of photothermal and chemodynamic modalities.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106728"},"PeriodicalIF":4.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471599","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 developed and characterized colchicine (COL) loaded-anionic nanocapsules prepared with poly(Ɛ-caprolactone) (NC-COL) and assessed their nanotoxicity in female Wistar rats, as per OECD Guideline 423, and C. elegans. The preformulation studies conducted using the components did not indicate any changes, implying compatibility in both the binary mixtures and the final formulation at temperatures below 100 °C. Blank nanocapsules (NC-B) and NC-COL nanocapsules exhibited sizes below 200 nm, monodisperse distribution, and high encapsulation efficiency (∼100 %). NC-B was significantly smaller than NC-COL, with all parameters remaining stable except for a slight reduction in pH over time. The in vitro COL release study showed that nanoencapsulation allows for the sustained bi-exponential release of COL. When exposed to the nanoencapsulated drug, C. elegans exhibited reduced survival rates, ranging from roughly 10–30 % at concentrations of 0.1 and 0.15 mg mL−1, respectively. Acute oral toxicity studies in rats showed no histological, oxidative, or biochemical damage at the tested doses of NC-COL, although triglyceride levels decreased at the highest dose of COL (10 mg kg−1). Our study successfully developed and characterized NC-COL, demonstrating its stability and controlled release properties. Despite the negative impact on C. elegans survival rates at higher doses, the rats did not exhibit adverse effects, regardless of the NC-COL dose, suggesting its potential safety for oral administration in therapeutic settings.
{"title":"Formulation development and toxicological assessment of colchicine-loaded nanocapsules","authors":"Ana Pozzato Funghetto-Ribeiro , Tamara Ramos Maciel , Camila de Oliveira Pacheco , Danielle Agarrayua , Anne Suély Savall , Eduarda Monteiro , Camila Cardoso , Marcílio Cunha-Filho , Guilherme Martins Gelfuso , Daiana da Silva Ávila , Simone Pinton , Sandra Elisa Haas","doi":"10.1016/j.jddst.2025.106722","DOIUrl":"10.1016/j.jddst.2025.106722","url":null,"abstract":"<div><div>This study developed and characterized colchicine (COL) loaded-anionic nanocapsules prepared with poly(Ɛ-caprolactone) (NC-COL) and assessed their nanotoxicity in female Wistar rats, as per OECD Guideline 423, and <em>C. elegans</em>. The preformulation studies conducted using the components did not indicate any changes, implying compatibility in both the binary mixtures and the final formulation at temperatures below 100 °C. Blank nanocapsules (NC-B) and NC-COL nanocapsules exhibited sizes below 200 nm, monodisperse distribution, and high encapsulation efficiency (∼100 %). NC-B was significantly smaller than NC-COL, with all parameters remaining stable except for a slight reduction in pH over time. The <em>in vitro</em> COL release study showed that nanoencapsulation allows for the sustained bi-exponential release of COL. When exposed to the nanoencapsulated drug, <em>C. elegans</em> exhibited reduced survival rates, ranging from roughly 10–30 % at concentrations of 0.1 and 0.15 mg mL<sup>−1</sup>, respectively. Acute oral toxicity studies in rats showed no histological, oxidative, or biochemical damage at the tested doses of NC-COL, although triglyceride levels decreased at the highest dose of COL (10 mg kg<sup>−1</sup>). Our study successfully developed and characterized NC-COL, demonstrating its stability and controlled release properties. Despite the negative impact on <em>C. elegans</em> survival rates at higher doses, the rats did not exhibit adverse effects, regardless of the NC-COL dose, suggesting its potential safety for oral administration in therapeutic settings.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106722"},"PeriodicalIF":4.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464714","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}
PEG remains a central focus of numerous preclinical and clinical studies owing to its distinctive advantages. Notably, the molecular weight of PEG and its modification density are critical factors influencing PEGylated nano drug delivery systems; however, this area remains inadequately explored. In this study, we assessed the effects of different PEG molecular weights (1000, 2000, 5000, and 10000 Da) and densities on the in vitro and in vivo properties of liposomes. Results showed that, in the in vitro studies, PEGylated liposomes with different PEG MWs and densities maintained adequate physical or serum stability compared to liposomes without any surface modification. Meanwhile, liposomes with varying PEG molecular weights and densities exhibited excellent membrane stability and integrity and showed little cytotoxicity against HUVEC and RAW 264.7. PEGylated liposomes with varying MWs and densities of PEG did not significantly affect the release of the fluorescence dye DiD and exhibited good stability. On the other hand, both MWs and densities of PEG had a major influence on the pharmacokinetic properties of liposomes. The optimal enhancement of in vivo circulation time was observed at a PEG density of 10 % for liposomes modified with PEG1000, PEG2000, and PEG5000, with group PEG2000 showing the highest AUC. For PEG with a molecular weight of 10000 Da, the elimination rate of PEGylated liposomes decreased as the density of PEG increased. These findings indicated that PEG MWs and densities both play critical roles in the formulation and physiochemical properties of nanomedicines, preliminarily providing guidance in selecting PEGs of suitable length and density in the designing of nanomedicines.
{"title":"Influence of polyethylene glycol coating of different molecular weights and densities on liposome properties","authors":"Hongjing Chen , Lin Wu , Huali Chen , Wen Wu , Qianyu Zhang","doi":"10.1016/j.jddst.2025.106725","DOIUrl":"10.1016/j.jddst.2025.106725","url":null,"abstract":"<div><div>PEG remains a central focus of numerous preclinical and clinical studies owing to its distinctive advantages. Notably, the molecular weight of PEG and its modification density are critical factors influencing PEGylated nano drug delivery systems; however, this area remains inadequately explored. In this study, we assessed the effects of different PEG molecular weights (1000, 2000, 5000, and 10000 Da) and densities on the <em>in vitro</em> and <em>in vivo</em> properties of liposomes. Results showed that, in the <em>in vitro</em> studies, PEGylated liposomes with different PEG MWs and densities maintained adequate physical or serum stability compared to liposomes without any surface modification. Meanwhile, liposomes with varying PEG molecular weights and densities exhibited excellent membrane stability and integrity and showed little cytotoxicity against HUVEC and RAW 264.7. PEGylated liposomes with varying MWs and densities of PEG did not significantly affect the release of the fluorescence dye DiD and exhibited good stability. On the other hand, both MWs and densities of PEG had a major influence on the pharmacokinetic properties of liposomes. The optimal enhancement of <em>in vivo</em> circulation time was observed at a PEG density of 10 % for liposomes modified with PEG<sub>1000</sub>, PEG<sub>2000,</sub> and PEG<sub>5000</sub>, with group PEG<sub>2000</sub> showing the highest AUC. For PEG with a molecular weight of 10000 Da, the elimination rate of PEGylated liposomes decreased as the density of PEG increased. These findings indicated that PEG MWs and densities both play critical roles in the formulation and physiochemical properties of nanomedicines, preliminarily providing guidance in selecting PEGs of suitable length and density in the designing of nanomedicines.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106725"},"PeriodicalIF":4.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445663","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 : 2025-02-17DOI: 10.1016/j.jddst.2025.106724
Nadia Mostafavi Nezhad , Hossein Kamali , Ali Asghar Sarchahi , Samira Jalalifar , Amir Amani , Fatemeh Oroojalian
Pharmaceutical treatment for glaucoma, an ocular illness characterized by elevated intraocular pressure (IOP), is hindered by challenges like limited bioavailability of drugs and difficulties in corneal delivery due to the human eye's unique anatomy. This research investigated the efficiency of liquid crystal nano cubosomes containing Dorzolamide and Timolol as a corneal drug delivery system. We used glycerol monooleate (GMO) and poloxamer 407 to prepare Dz/TM cubosomes. The mixture was stirred, homogenized, and probed. Dynamic light scattering (DLS) was used to evaluate the size, PDI, and zeta potential of cubosomes, and their physicochemical properties, phase behavior, in vitro release kinetics, cytotoxicity, and pharmacodynamic and pharmacokinetic features were also investigated. The average size, zeta potential, and PDI of the cubosomes were 143.5 ± 2.3 nm, −26.3 ± 1.7 mV, and 0.164 ± 0.014, respectively. Drug encapsulation efficiency was 84.5 ± 2.1 % for Dz and 91.3 ± 2.7 % for TM. In vitro release testing showed a slow-release pattern for both Dz and TM reaching the maximal dose after 24 h. In vivo evaluations showed a considerable reduction in IOP from 27.28 to 19.40 within 4 h of administration and an increase in the retention time of both drugs. Pharmacokinetic studies revealed that cubosomes had longer bioavailability than Zilomole®, and Dz/TM cubosomes offered higher areas under the curve (AUC) for both drugs compared to available marketed eye drops. The prepared formulation led to no significant histopathological damage to the cornea, indicating its optimal biocompatibility. Overall, this formulation seems to be a safe constant-release drug carrier to deliver medications to the cornea.
{"title":"Investigating the efficacy of liquid crystal nano cubosomes containing dorzolamide and timolol for drug delivery to the cornea","authors":"Nadia Mostafavi Nezhad , Hossein Kamali , Ali Asghar Sarchahi , Samira Jalalifar , Amir Amani , Fatemeh Oroojalian","doi":"10.1016/j.jddst.2025.106724","DOIUrl":"10.1016/j.jddst.2025.106724","url":null,"abstract":"<div><div>Pharmaceutical treatment for glaucoma, an ocular illness characterized by elevated intraocular pressure (IOP), is hindered by challenges like limited bioavailability of drugs and difficulties in corneal delivery due to the human eye's unique anatomy. This research investigated the efficiency of liquid crystal nano cubosomes containing Dorzolamide and Timolol as a corneal drug delivery system. We used glycerol monooleate (GMO) and poloxamer 407 to prepare Dz/TM cubosomes. The mixture was stirred, homogenized, and probed. Dynamic light scattering (DLS) was used to evaluate the size, PDI, and zeta potential of cubosomes, and their physicochemical properties, phase behavior, in vitro release kinetics, cytotoxicity, and pharmacodynamic and pharmacokinetic features were also investigated. The average size, zeta potential, and PDI of the cubosomes were 143.5 ± 2.3 nm, −26.3 ± 1.7 mV, and 0.164 ± 0.014, respectively. Drug encapsulation efficiency was 84.5 ± 2.1 % for Dz and 91.3 ± 2.7 % for TM. In vitro release testing showed a slow-release pattern for both Dz and TM reaching the maximal dose after 24 h. In vivo evaluations showed a considerable reduction in IOP from 27.28 to 19.40 within 4 h of administration and an increase in the retention time of both drugs. Pharmacokinetic studies revealed that cubosomes had longer bioavailability than Zilomole®, and Dz/TM cubosomes offered higher areas under the curve (AUC) for both drugs compared to available marketed eye drops. The prepared formulation led to no significant histopathological damage to the cornea, indicating its optimal biocompatibility. Overall, this formulation seems to be a safe constant-release drug carrier to deliver medications to the cornea.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106724"},"PeriodicalIF":4.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464715","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 investigates the innovative application of rosmarinic acid (RA)-loaded Resomer RG 502 H-based nanoparticles (NPs) in enhancing therapeutic efficacy against oxidative stress and microbial infections. Rosmarinic acid, a natural polyphenol with significant pharmacological properties, has demonstrated potential in treating various diseases, including cancer, diabetes, and inflammatory disorders. However, its clinical utility is hampered by poor water solubility and bioavailability. To address these challenges, we employed a nanoprecipitation technique to create biodegradable PLGA-based NPs that encapsulate RA effectively. The formulation showed uniformity with a particle size of 217.7 nm ± 4.3 and a PDI of 0.129 ± 0.007. A study was conducted with trehalose to ensure stability during storage. The resultant NPs not only exhibit high encapsulation efficiency (≈72.8 %) but also provide sustained release profiles for 72 h, which are crucial for maximizing RA's therapeutic effects. DSC, FT-IR, and 1H-NMR analyses confirmed the encapsulation and structural integrity of the formulation. Pharmacological evaluations, including the effects of RA and B-RA-NP on NIH/3T3 cell viability, the evaluation of optimal tBHP concentration, and exposure time for assessing antioxidant activity, reveal that these NPs significantly enhance the antioxidant activity of RA while exhibiting potent antimicrobial effects against a spectrum of pathogenic microorganisms. By leveraging nanotechnology for drug delivery, we present a promising strategy to improve the bioavailability and efficacy of RA, thus advancing its application in therapeutic formulations. The findings underscore the transformative potential of nanotechnology in enhancing the clinical relevance of natural compounds, paving the way for novel therapeutic strategies in pharmaceutical applications.
{"title":"Evaluation of antimicrobial properties and antioxidant activity of rosmarinic acid loaded Resomer RG 502 H based nanoparticles against tert-butyl hydroperoxide-induced oxidative stress: A detailed formulation, characterization and efficacy determination study","authors":"Büşra Solak , Pervin Soyer , Elif Kaya-Tilki , A. Alper Öztürk","doi":"10.1016/j.jddst.2025.106721","DOIUrl":"10.1016/j.jddst.2025.106721","url":null,"abstract":"<div><div>This study investigates the innovative application of rosmarinic acid (RA)-loaded Resomer RG 502 H-based nanoparticles (NPs) in enhancing therapeutic efficacy against oxidative stress and microbial infections. Rosmarinic acid, a natural polyphenol with significant pharmacological properties, has demonstrated potential in treating various diseases, including cancer, diabetes, and inflammatory disorders. However, its clinical utility is hampered by poor water solubility and bioavailability. To address these challenges, we employed a nanoprecipitation technique to create biodegradable PLGA-based NPs that encapsulate RA effectively. The formulation showed uniformity with a particle size of 217.7 nm ± 4.3 and a PDI of 0.129 ± 0.007. A study was conducted with trehalose to ensure stability during storage. The resultant NPs not only exhibit high encapsulation efficiency (≈72.8 %) but also provide sustained release profiles for 72 h, which are crucial for maximizing RA's therapeutic effects. DSC, FT-IR, and <sup>1</sup>H-NMR analyses confirmed the encapsulation and structural integrity of the formulation. Pharmacological evaluations, including the effects of RA and B-RA-NP on NIH/3T3 cell viability, the evaluation of optimal tBHP concentration, and exposure time for assessing antioxidant activity, reveal that these NPs significantly enhance the antioxidant activity of RA while exhibiting potent antimicrobial effects against a spectrum of pathogenic microorganisms. By leveraging nanotechnology for drug delivery, we present a promising strategy to improve the bioavailability and efficacy of RA, thus advancing its application in therapeutic formulations. The findings underscore the transformative potential of nanotechnology in enhancing the clinical relevance of natural compounds, paving the way for novel therapeutic strategies in pharmaceutical applications.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106721"},"PeriodicalIF":4.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453017","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 : 2025-02-17DOI: 10.1016/j.jddst.2025.106720
Paniz Ranjbaran , Mehdi Esfandyari-Manesh , Alaleh Yourdkhani , Mohammad Hossein Ghahremani , Rassoul Dinarvand
One of the most common types of bone cancer is osteosarcoma. Currently a combination of therapies including surgery, chemotherapy, and radiation therapy is used. Bone defects, re-formation of the tumor, or remaining tumor cells after the surgery are the main challenges of osteosarcoma treatments. Scaffolds can be used to overcome the bone defects problem. In this study, we aim to fabricate a bilayer scaffold with the capacity of avoiding tumor recurrence and stimulating bone regeneration which brings a novel idea for osteosarcoma treatments. First, methotrexate was encapsulated in PLGA microspheres with 13.5 % loading capacity. Then, coaxial extrusion-based 3D printer via a customized bilayer core-shell nozzle was employed to fabricate the scaffold. The implanted scaffold was printed by using gelatin methacrylol (GelMA) hydrogel containing methotrexate microspheres in the outer layer for anticancer drug delivery, and GelMA/alginate hydrogel containing nanohydroxyapatite and nanosilica in the inner layer for bone regeneration. The outer layer of the scaffold had rapidly degraded within 20 days and it played a great role in drug delivery and inhibiting the tumor cells’ growth. The inner layer with 4 % nanosilica had slow degradation rate at about 50 % in 60 days and it showed the highest mechanical strength with 225 kPa. Regarding osteogenesis property, ALP enzyme activity was increased considerably within 3 weeks. Also, significant increase in osteogenesis markers of RUNX2, OPN, and COL1A1 was observed. In addition to drug delivery at the tumor site, this bilayer scaffold could be a platform for the placement of healthy bone cells after drug delivery.
{"title":"3D printed core/shell scaffold based on nano/microspheric hydrogel for osteosarcoma anticancer delivery and bone regeneration","authors":"Paniz Ranjbaran , Mehdi Esfandyari-Manesh , Alaleh Yourdkhani , Mohammad Hossein Ghahremani , Rassoul Dinarvand","doi":"10.1016/j.jddst.2025.106720","DOIUrl":"10.1016/j.jddst.2025.106720","url":null,"abstract":"<div><div>One of the most common types of bone cancer is osteosarcoma. Currently a combination of therapies including surgery, chemotherapy, and radiation therapy is used. Bone defects, re-formation of the tumor, or remaining tumor cells after the surgery are the main challenges of osteosarcoma treatments. Scaffolds can be used to overcome the bone defects problem. In this study, we aim to fabricate a bilayer scaffold with the capacity of avoiding tumor recurrence and stimulating bone regeneration which brings a novel idea for osteosarcoma treatments. First, methotrexate was encapsulated in PLGA microspheres with 13.5 % loading capacity. Then, coaxial extrusion-based 3D printer via a customized bilayer core-shell nozzle was employed to fabricate the scaffold. The implanted scaffold was printed by using gelatin methacrylol (GelMA) hydrogel containing methotrexate microspheres in the outer layer for anticancer drug delivery, and GelMA/alginate hydrogel containing nanohydroxyapatite and nanosilica in the inner layer for bone regeneration. The outer layer of the scaffold had rapidly degraded within 20 days and it played a great role in drug delivery and inhibiting the tumor cells’ growth. The inner layer with 4 % nanosilica had slow degradation rate at about 50 % in 60 days and it showed the highest mechanical strength with 225 kPa. Regarding osteogenesis property, ALP enzyme activity was increased considerably within 3 weeks. Also, significant increase in osteogenesis markers of RUNX2, OPN, and COL1A1 was observed. In addition to drug delivery at the tumor site, this bilayer scaffold could be a platform for the placement of healthy bone cells after drug delivery.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106720"},"PeriodicalIF":4.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445660","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 : 2025-02-16DOI: 10.1016/j.jddst.2025.106719
Yuhang Wang , Jiang Yu , Xuejing Li , Haolin Zhang , Tengfei Zhou , Yiguo Jiang , Yongjun Wang
Inflammatory arthritis primarily involves rheumatoid arthritis (RA) and inflammatory osteoarthritis (OA), both characterized by shared inflammation in the articular joints and cartilage degeneration. These conditions lead to joint pain, loss of function, and a decline in quality of life. Triamcinolone acetonide (TA), an intermediate-acting synthetic glucocorticoid, is widely used as an anti-inflammatory agent for the treatment of inflammatory arthritis. However, its clinical application faces challenges such as rapid clearance from the joint cavity following intra-articular (IA) administration, the risk of joint damage with repeated injections, and the invasive nature of the IA injection route. To address these drawbacks, we propose sucrose acetate isobutyrate (SAIB), a biocompatible matrix, as a promising strategy for sustained drug release via intramuscular (IM) injection. Building on this approach, we designed a gallic acid-modified triamcinolone acetonide derivative (TA-GA) and incorporated it into the SAIB matrix to create the TA-GA-SAIB depot. The modification of TA with gallic acid (GA) effectively mitigates the burst release commonly observed in SAIB formulations, attributed to hydrogen bonding interactions between TA-GA and the SAIB matrix. Benzyl alcohol (BA) was selected as the optimal solvent to achieve minimal burst release during the in vitro drug release study. The TA-GA-SAIB depot exhibited sustained in vivo drug release, enhanced anti-inflammatory effects, and significant improvement in cartilage damage, along with excellent safety and biocompatibility. The synergy between the SAIB matrix and TA-GA not only enables sustained drug release but also improves therapeutic efficacy, making it a promising system for the treatment of inflammatory arthritis via intramuscular administration.
{"title":"Enhanced inflammatory arthritis therapy with gallic acid-modified triamcinolone acetonide: A sucrose acetate isobutyrate-based sustained release depot","authors":"Yuhang Wang , Jiang Yu , Xuejing Li , Haolin Zhang , Tengfei Zhou , Yiguo Jiang , Yongjun Wang","doi":"10.1016/j.jddst.2025.106719","DOIUrl":"10.1016/j.jddst.2025.106719","url":null,"abstract":"<div><div>Inflammatory arthritis primarily involves rheumatoid arthritis (RA) and inflammatory osteoarthritis (OA), both characterized by shared inflammation in the articular joints and cartilage degeneration. These conditions lead to joint pain, loss of function, and a decline in quality of life. Triamcinolone acetonide (TA), an intermediate-acting synthetic glucocorticoid, is widely used as an anti-inflammatory agent for the treatment of inflammatory arthritis. However, its clinical application faces challenges such as rapid clearance from the joint cavity following intra-articular (IA) administration, the risk of joint damage with repeated injections, and the invasive nature of the IA injection route. To address these drawbacks, we propose sucrose acetate isobutyrate (SAIB), a biocompatible matrix, as a promising strategy for sustained drug release via intramuscular (IM) injection. Building on this approach, we designed a gallic acid-modified triamcinolone acetonide derivative (TA-GA) and incorporated it into the SAIB matrix to create the TA-GA-SAIB depot. The modification of TA with gallic acid (GA) effectively mitigates the burst release commonly observed in SAIB formulations, attributed to hydrogen bonding interactions between TA-GA and the SAIB matrix. Benzyl alcohol (BA) was selected as the optimal solvent to achieve minimal burst release during the in vitro drug release study. The TA-GA-SAIB depot exhibited sustained in vivo drug release, enhanced anti-inflammatory effects, and significant improvement in cartilage damage, along with excellent safety and biocompatibility. The synergy between the SAIB matrix and TA-GA not only enables sustained drug release but also improves therapeutic efficacy, making it a promising system for the treatment of inflammatory arthritis via intramuscular administration.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106719"},"PeriodicalIF":4.5,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143430165","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 : 2025-02-15DOI: 10.1016/j.jddst.2025.106718
Wei-Jhe Syu , Yihenew Simegniew Birhan , Govindan Sivakumar , Ming-Gen Tsai , Cun-Zhao Li , Ping-Shan Lai
Multimodal cancer treatment regimens that combine diagnosis with therapy have received considerable attention in recent years. This study focused on the fabrication of near-infrared (NIR)-activated Fe3O4-DNA-DTPA-Gd NPs intended for imaging, thermotherapy, and chemotherapy of cancer. The successful synthesis of Fe3O4, oligonucleotide conjugates, and DTPA-Gd was verified by XRD, FTIR, 1H NMR, and ICP-OES. The bare and citrate-coated Fe3O4 aggregated into cubic NPs of 100 nm in size and showed desirable photothermal conversion efficiency of 18.26 %. In addition, the DOX@Fe3O4-DNA-DTPA-Gd NPs could disassemble and release DOX when the temperature reached 42 °C due to the denaturation of oligonucleotide moiety upon 808 nm laser light irradiation (0.65 W/cm2). Moreover, the cellular trafficking study revealed the presence of intense red fluorescence in the cytosol of MCF-7/ADR cells due to the internalization of DOX@Fe3O4-DNA-DTPA-Gd NPs. Under NIR light illumination, both Fe3O4-DNA-DTPA-Gd and DOX@Fe3O4-DNA-DTPA-Gd NPs suppressed the proliferation of MCF-7/ADR cells, 38.31 % and 19.40 % cell viability at 20 μM DOX and 157 ppm Fe3+ concentration, respectively. Furthermore, the Fe3O4-DNA-DTPA-Gd NPs displayed T2/T1 switchable property, in the presence of applied magnetic field, suggesting the feasibility of the design for multimodal MRI, photothermic and chemotherapeutic treatment of cancer.
{"title":"NIR-activated magnetic resonance nanoprobes for combined photothermal therapy and chemotherapy of cancer","authors":"Wei-Jhe Syu , Yihenew Simegniew Birhan , Govindan Sivakumar , Ming-Gen Tsai , Cun-Zhao Li , Ping-Shan Lai","doi":"10.1016/j.jddst.2025.106718","DOIUrl":"10.1016/j.jddst.2025.106718","url":null,"abstract":"<div><div>Multimodal cancer treatment regimens that combine diagnosis with therapy have received considerable attention in recent years. This study focused on the fabrication of near-infrared (NIR)-activated Fe<sub>3</sub>O<sub>4</sub>-DNA-DTPA-Gd NPs intended for imaging, thermotherapy, and chemotherapy of cancer. The successful synthesis of Fe<sub>3</sub>O<sub>4</sub>, oligonucleotide conjugates, and DTPA-Gd was verified by XRD, FTIR, <sup>1</sup>H NMR, and ICP-OES. The bare and citrate-coated Fe<sub>3</sub>O<sub>4</sub> aggregated into cubic NPs of 100 nm in size and showed desirable photothermal conversion efficiency of 18.26 %. In addition, the DOX@Fe<sub>3</sub>O<sub>4</sub>-DNA-DTPA-Gd NPs could disassemble and release DOX when the temperature reached 42 °C due to the denaturation of oligonucleotide moiety upon 808 nm laser light irradiation (0.65 W/cm<sup>2</sup>). Moreover, the cellular trafficking study revealed the presence of intense red fluorescence in the cytosol of MCF-7/ADR cells due to the internalization of DOX@Fe<sub>3</sub>O<sub>4</sub>-DNA-DTPA-Gd NPs. Under NIR light illumination, both Fe<sub>3</sub>O<sub>4</sub>-DNA-DTPA-Gd and DOX@Fe<sub>3</sub>O<sub>4</sub>-DNA-DTPA-Gd NPs suppressed the proliferation of MCF-7/ADR cells, 38.31 % and 19.40 % cell viability at 20 μM DOX and 157 ppm Fe<sup>3+</sup> concentration, respectively. Furthermore, the Fe<sub>3</sub>O<sub>4</sub>-DNA-DTPA-Gd NPs displayed <em>T</em><sub><em>2</em></sub>/<em>T</em><sub><em>1</em></sub> switchable property, in the presence of applied magnetic field, suggesting the feasibility of the design for multimodal MRI, photothermic and chemotherapeutic treatment of cancer.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106718"},"PeriodicalIF":4.5,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445661","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 : 2025-02-15DOI: 10.1016/j.jddst.2025.106716
Yuanxin Pian , Yan Hao , Yuxin Guo , Shiqi Wu , Saijiao Tang , Jiaqi Li , Xinya Lu , Xiaoya Sun , Zhaowen Tan , Tianyu Zhu , Yuxiang Tang , Defeng Xu , Hang Hu
Facile and efficient drug loading and delivery strategies hold paramount importance in the development of advanced pharmaceutical formulations, enhancing both the efficacy and accessibility of treatments. In this study, we successfully prepared dimethylcurcumin (DMC)-loaded α-crocin nanoparticles with varying drug loadings (15.2 % and 21.7 %) using a solvent diffusion method, which exhibit excellent lyophilization stability, relatively small and uniform particle sizes. DMC is encapsulated in an amorphous state within α-crocin nanoparticles, forming strong π-π stacking interactions. Dissipative particle dynamics simulations and transmission electron microscope images confirm the core-shell structure, with DMC aggregates forming the cores and α-crocin coating the surfaces. The drug loading studies on various drugs with different structure and properties show that hydrophobic drugs with π-conjugated systems and planar structures can be efficiently encapsulated with α-crocin. The nanoparticles exhibit sustained drug release in pH 7.4 and pH 5.0 conditions and demonstrate enhanced antitumor activity in vitro compared to free drugs, with DMC@α-Crocin (15.2 %) nanoparticles showing superior performance due to higher cellular uptake. Pharmacokinetic study reveals prolonged blood half-life and increased area under curve for DMC@α-Crocin (15.2 %) nanoparticles, indicating improved drug delivery. This work validates the potential of α-crocin-based drug encapsulation for enhanced cellular uptake, antitumor activity, and prolonged blood circulation, providing new insights into the development of efficient drug delivery system.
{"title":"Exploration of using α-crocin for drug encapsulation and delivery","authors":"Yuanxin Pian , Yan Hao , Yuxin Guo , Shiqi Wu , Saijiao Tang , Jiaqi Li , Xinya Lu , Xiaoya Sun , Zhaowen Tan , Tianyu Zhu , Yuxiang Tang , Defeng Xu , Hang Hu","doi":"10.1016/j.jddst.2025.106716","DOIUrl":"10.1016/j.jddst.2025.106716","url":null,"abstract":"<div><div>Facile and efficient drug loading and delivery strategies hold paramount importance in the development of advanced pharmaceutical formulations, enhancing both the efficacy and accessibility of treatments. In this study, we successfully prepared dimethylcurcumin (DMC)-loaded α-crocin nanoparticles with varying drug loadings (15.2 % and 21.7 %) using a solvent diffusion method, which exhibit excellent lyophilization stability, relatively small and uniform particle sizes. DMC is encapsulated in an amorphous state within α-crocin nanoparticles, forming strong π-π stacking interactions. Dissipative particle dynamics simulations and transmission electron microscope images confirm the core-shell structure, with DMC aggregates forming the cores and α-crocin coating the surfaces. The drug loading studies on various drugs with different structure and properties show that hydrophobic drugs with π-conjugated systems and planar structures can be efficiently encapsulated with α-crocin. The nanoparticles exhibit sustained drug release in pH 7.4 and pH 5.0 conditions and demonstrate enhanced antitumor activity in vitro compared to free drugs, with DMC@α-Crocin (15.2 %) nanoparticles showing superior performance due to higher cellular uptake. Pharmacokinetic study reveals prolonged blood half-life and increased area under curve for DMC@α-Crocin (15.2 %) nanoparticles, indicating improved drug delivery. This work validates the potential of α-crocin-based drug encapsulation for enhanced cellular uptake, antitumor activity, and prolonged blood circulation, providing new insights into the development of efficient drug delivery system.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106716"},"PeriodicalIF":4.5,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436828","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 : 2025-02-15DOI: 10.1016/j.jddst.2025.106711
Iqra Afzal, Ahmad Zeb, Danish Mazhar, Jehan Zeb Khan, Sidra Altaf, Qurat ul Ain, Hussain Ali
The current study evaluates the efficacy of tofacitinib (Tofa) loaded folate grafted transfersomes (FA-CS-Tofa-Tfs) for transdermal delivery to treat breast cancer. Tofa-Tfs were prepared and optimized by using Box Behnken design of experiment and then coated with FA-CS by electrostatic interaction. FA-CS-Tofa-Tfs were subsequently embedded in Carbopol gel containing Eucalyptus oil (EO) as permeation enhancer to enhance drug bioavailability. The prepared formulation was then evaluated for physicochemical and in vitro characterization. FA-CS-Tofa-Tfs were spherical in shape with a vesicle size of 232.57 ± 5.95 nm, % entrapment efficiency (EE) of 86.89 ± 5.13, zeta potential of +22.17 ± 5.05 and release profile of the designed system presented sustained release of Tofa for 48 h. The ex vivo permeation studies displayed 10.30 folds enhanced permeation for FA-CS-Tofa-Tfs gel with EO when compared with Tofa gel. In vitro cytotoxicity study on MCF-7 breast cancer cells indicated 8.67 folds lower IC50 value for FA-CS-Tofa-Tfs gel in contrast to Tofa. Flow cytometry results for cell apoptosis indicated significantly enhanced early and late apoptosis for FA-CS-Tofa-Tfs gel in comparison to pure Tofa. These substantial outcomes encourages that biocompatible FA-CS-Tofa-Tfs could be employed as a promising strategy to actively target and treat breast cancer via transdermal route.
{"title":"Folic acid grafted tofacitinib loaded targeted transfersomes for transdermal delivery against breast cancer","authors":"Iqra Afzal, Ahmad Zeb, Danish Mazhar, Jehan Zeb Khan, Sidra Altaf, Qurat ul Ain, Hussain Ali","doi":"10.1016/j.jddst.2025.106711","DOIUrl":"10.1016/j.jddst.2025.106711","url":null,"abstract":"<div><div>The current study evaluates the efficacy of tofacitinib (Tofa) loaded folate grafted transfersomes (FA-CS-Tofa-Tfs) for transdermal delivery to treat breast cancer. Tofa-Tfs were prepared and optimized by using Box Behnken design of experiment and then coated with FA-CS by electrostatic interaction. FA-CS-Tofa-Tfs were subsequently embedded in Carbopol gel containing Eucalyptus oil (EO) as permeation enhancer to enhance drug bioavailability. The prepared formulation was then evaluated for physicochemical and <em>in vitro</em> characterization. FA-CS-Tofa-Tfs were spherical in shape with a vesicle size of 232.57 ± 5.95 nm, % entrapment efficiency (EE) of 86.89 ± 5.13, zeta potential of +22.17 ± 5.05 and release profile of the designed system presented sustained release of Tofa for 48 h. The <em>ex vivo</em> permeation studies displayed 10.30 folds enhanced permeation for FA-CS-Tofa-Tfs gel with EO when compared with Tofa gel. <em>In vitro</em> cytotoxicity study on MCF-7 breast cancer cells indicated 8.67 folds lower IC<sub>50</sub> value for FA-CS-Tofa-Tfs gel in contrast to Tofa. Flow cytometry results for cell apoptosis indicated significantly enhanced early and late apoptosis for FA-CS-Tofa-Tfs gel in comparison to pure Tofa. These substantial outcomes encourages that biocompatible FA-CS-Tofa-Tfs could be employed as a promising strategy to actively target and treat breast cancer via transdermal route.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106711"},"PeriodicalIF":4.5,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436827","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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