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3D printing as a solution for tablet splitting challenges dedicated to the Chagas disease treatment 用 3D 打印技术解决南美锥虫病治疗中的药片分割难题
IF 4.5 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-25 DOI: 10.1016/j.jddst.2025.106745
Giselle R. Bedogni , Ana Luiza Lima , Idejan P. Gross , Tais Gratieri , Guilherme M. Gelfuso , María C. Lamas , Marcilio Cunha-Filho , Claudio J. Salomon
Chagas disease is a potentially fatal neglected infection affecting both infants and adults. Currently, only benznidazole (BNZ) and nifurtimox (NFX) are approved for the treatment, and there is a considerable need for dosage adjustments to meet individual patient conditions. However, as the commercial options are limited, splitting commercial tablets of BNZ and NFX is common practice. Thus, this study aimed to evaluate, for the first time, the splitting behavior of such commercial tablets. Average mass, drug content, friability, and hardness were evaluated using two subdivision methods. Additionally, an in-use stability of split tablets was performed. Lastly, BNZ and NFX tablets produced by 3D printing with different dosages were proposed as an alternative method of personalizing treatment. The findings of this work indicated that the subdivision method was not a relevant variable in obtaining halves, although the splitting device was shown to deliver better results in obtaining quarters. In-use stability demonstrated that the split tablets were chemically preserved under forced storage conditions for at least 15 days. Even though moisture adsorption occurred, no changes in drug characteristic signals in the infrared spectra were observed. The physical and mechanical properties were compromised after splitting, leading to multiple fragmentation. In addition, the high variation in mass and mass loss led to high dosage variations and, consequently, may increase the treatment risk. Therefore, splitting these tablets into quarters should be discouraged. Thus, BNZ and NFX 3D printing tablets were prepared to avoid the splitting issues of the marketed tablets. This approach proves to be a promising option to minimize the risks associated with tablet splitting while providing a more reliable and flexible method for dose adjustment.
{"title":"3D printing as a solution for tablet splitting challenges dedicated to the Chagas disease treatment","authors":"Giselle R. Bedogni ,&nbsp;Ana Luiza Lima ,&nbsp;Idejan P. Gross ,&nbsp;Tais Gratieri ,&nbsp;Guilherme M. Gelfuso ,&nbsp;María C. Lamas ,&nbsp;Marcilio Cunha-Filho ,&nbsp;Claudio J. Salomon","doi":"10.1016/j.jddst.2025.106745","DOIUrl":"10.1016/j.jddst.2025.106745","url":null,"abstract":"<div><div>Chagas disease is a potentially fatal neglected infection affecting both infants and adults. Currently, only benznidazole (BNZ) and nifurtimox (NFX) are approved for the treatment, and there is a considerable need for dosage adjustments to meet individual patient conditions. However, as the commercial options are limited, splitting commercial tablets of BNZ and NFX is common practice. Thus, this study aimed to evaluate, for the first time, the splitting behavior of such commercial tablets. Average mass, drug content, friability, and hardness were evaluated using two subdivision methods. Additionally, an in-use stability of split tablets was performed. Lastly, BNZ and NFX tablets produced by 3D printing with different dosages were proposed as an alternative method of personalizing treatment. The findings of this work indicated that the subdivision method was not a relevant variable in obtaining halves, although the splitting device was shown to deliver better results in obtaining quarters. In-use stability demonstrated that the split tablets were chemically preserved under forced storage conditions for at least 15 days. Even though moisture adsorption occurred, no changes in drug characteristic signals in the infrared spectra were observed. The physical and mechanical properties were compromised after splitting, leading to multiple fragmentation. In addition, the high variation in mass and mass loss led to high dosage variations and, consequently, may increase the treatment risk. Therefore, splitting these tablets into quarters should be discouraged. Thus, BNZ and NFX 3D printing tablets were prepared to avoid the splitting issues of the marketed tablets. This approach proves to be a promising option to minimize the risks associated with tablet splitting while providing a more reliable and flexible method for dose adjustment.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106745"},"PeriodicalIF":4.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520598","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}
引用次数: 0
LC-MS/MS profiling and immunomodulatory potential of green-synthesized zinc oxide nanoparticles using Cordia sebestena leaves against chromium-induced acute lung injury in rats
IF 4.5 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-24 DOI: 10.1016/j.jddst.2025.106750
Nabil A. Shoman , Abeer Salama , Firas G. Abbas , Hagar H. Mourad , Haidy A. Abbas
This study evaluates the green synthesized zinc oxide nanoparticles (ZnO NPs) using Cordia sebestena leaves (CS) methanolic extract and evaluates their immunomodulatory potential in treating chromium-induced acute lung injury (ALI) in a rat model. A 32 full factorial design, utilizing response surface methodology, was utilized to optimize key parameters, including extract amount, metallic salt concentration, and pH, to control nanoparticle size, polydispersity index, and zeta potential. The optimal formulation (5 g plant extract, 5 g zinc acetate, pH 11) achieved an overall desirability of 0.996. UV–Visible spectroscopy confirmed a characteristic peak at 360 nm (optical band gap: 3.2 eV), while Fourier Transform Infrared analysis identified biofunctional groups stabilizing the nanoparticles. Transmission electron microscopy revealed hexagonal particles with a crystallite size of around 80 nm, consistent with dynamic light scattering data. Thermogravimetric analysis demonstrated high thermal stability. CS-ZnO NPs significantly enhanced lung antioxidant capacity (increased GSH levels) and reduced oxidative stress (MDA), pro-inflammatory cytokines (TNF-α, IL-17), and signaling molecules (Akt, PI3K). AMPK activation was also markedly improved in the CS-ZnO NPs-treated group. Dereplication analysis of the Cordia sebestena leaves methanolic extract was conducted using Q-TOF LC/MS/MS; metabolic profiling identified 33 compounds, which are classified into various chemical groups, including flavonoids, phenolic acids, stilbenes, organic acids, and fatty acids. These findings suggest that CS-ZnO NPs exhibit potent pulmonary protective effects against chromium-induced ALI through their antioxidant, anti-inflammatory, and immunomodulatory properties, underscoring their potential for sustainable biomedical applications.
{"title":"LC-MS/MS profiling and immunomodulatory potential of green-synthesized zinc oxide nanoparticles using Cordia sebestena leaves against chromium-induced acute lung injury in rats","authors":"Nabil A. Shoman ,&nbsp;Abeer Salama ,&nbsp;Firas G. Abbas ,&nbsp;Hagar H. Mourad ,&nbsp;Haidy A. Abbas","doi":"10.1016/j.jddst.2025.106750","DOIUrl":"10.1016/j.jddst.2025.106750","url":null,"abstract":"<div><div>This study evaluates the green synthesized zinc oxide nanoparticles (ZnO NPs) using <em>Cordia sebestena</em> leaves (CS) methanolic extract and evaluates their immunomodulatory potential in treating chromium-induced acute lung injury (ALI) in a rat model. A 3<sup>2</sup> full factorial design, utilizing response surface methodology, was utilized to optimize key parameters, including extract amount, metallic salt concentration, and pH, to control nanoparticle size, polydispersity index, and zeta potential. The optimal formulation (5 g plant extract, 5 g zinc acetate, pH 11) achieved an overall desirability of 0.996. UV–Visible spectroscopy confirmed a characteristic peak at 360 nm (optical band gap: 3.2 eV), while Fourier Transform Infrared analysis identified biofunctional groups stabilizing the nanoparticles. Transmission electron microscopy revealed hexagonal particles with a crystallite size of around 80 nm, consistent with dynamic light scattering data. Thermogravimetric analysis demonstrated high thermal stability. CS-ZnO NPs significantly enhanced lung antioxidant capacity (increased GSH levels) and reduced oxidative stress (MDA), pro-inflammatory cytokines (TNF-α, IL-17), and signaling molecules (Akt, PI3K). AMPK activation was also markedly improved in the CS-ZnO NPs-treated group. Dereplication analysis of the <em>Cordia sebestena</em> leaves methanolic extract was conducted using Q-TOF LC/MS/MS; metabolic profiling identified 33 compounds, which are classified into various chemical groups, including flavonoids, phenolic acids, stilbenes, organic acids, and fatty acids. These findings suggest that CS-ZnO NPs exhibit potent pulmonary protective effects against chromium-induced ALI through their antioxidant, anti-inflammatory, and immunomodulatory properties, underscoring their potential for sustainable biomedical applications.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106750"},"PeriodicalIF":4.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511366","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}
引用次数: 0
Hyaluronic acid incorporation into hybrid alginate-based bioinks promotes long term viability and controlled release of 3D embedded scaffolds mesenchymal stem cells in absence of Dimethyl Sulfoxide cryoprotectant
IF 4.5 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-23 DOI: 10.1016/j.jddst.2025.106749
Kaoutar Ziani , Javier Plou , Laura Saenz-del-Burgo , Isabel García , Jesús Ciriza , Jose Luis Pedraz
Cryopreservation is critical in 3D bioprinting to ensure availability for clinical use and long-term storage. We have studied the incorporation of hyaluronic acid (Ha) into an alginate-nanocellulose bioink to enhance scaffold properties and reduce reliance on dimethyl sulfoxide (DMSO), a traditional, but toxic cryoprotectant. Our findings show that Ha significantly improves biomaterial ink viscoelasticity, even after cryopreservation at ultra-low temperatures. Moreover, scaffolds incorporating Ha exhibited increased roughness and porosity and mechanical testing indicated that cryopreserved scaffolds with Ha were more durable. Interestingly, scaffolds without DMSO maintained high cell viability and metabolic activity, suggesting effective cryoprotection with reduced cytotoxicity. In conclusion, incorporating Ha into bioinks enhances scaffold properties and enables successful cryopreservation without DMSO, paving the way for safer and more efficient bioinks in tissue engineering and regenerative medicine.
{"title":"Hyaluronic acid incorporation into hybrid alginate-based bioinks promotes long term viability and controlled release of 3D embedded scaffolds mesenchymal stem cells in absence of Dimethyl Sulfoxide cryoprotectant","authors":"Kaoutar Ziani ,&nbsp;Javier Plou ,&nbsp;Laura Saenz-del-Burgo ,&nbsp;Isabel García ,&nbsp;Jesús Ciriza ,&nbsp;Jose Luis Pedraz","doi":"10.1016/j.jddst.2025.106749","DOIUrl":"10.1016/j.jddst.2025.106749","url":null,"abstract":"<div><div>Cryopreservation is critical in 3D bioprinting to ensure availability for clinical use and long-term storage. We have studied the incorporation of hyaluronic acid (Ha) into an alginate-nanocellulose bioink to enhance scaffold properties and reduce reliance on dimethyl sulfoxide (DMSO), a traditional, but toxic cryoprotectant. Our findings show that Ha significantly improves biomaterial ink viscoelasticity, even after cryopreservation at ultra-low temperatures. Moreover, scaffolds incorporating Ha exhibited increased roughness and porosity and mechanical testing indicated that cryopreserved scaffolds with Ha were more durable. Interestingly, scaffolds without DMSO maintained high cell viability and metabolic activity, suggesting effective cryoprotection with reduced cytotoxicity. In conclusion, incorporating Ha into bioinks enhances scaffold properties and enables successful cryopreservation without DMSO, paving the way for safer and more efficient bioinks in tissue engineering and regenerative medicine.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106749"},"PeriodicalIF":4.5,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489047","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}
引用次数: 0
Greener nanomaterials for soft tissue regeneration: Diagnostic and therapeutic advances
IF 4.5 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-22 DOI: 10.1016/j.jddst.2025.106747
Garima , Deepika Sharma , Neeraj Mittal
Soft tissue injuries and organ dysfunction present significant medical challenges, however, nanotechnology using green chemistry offers a transformative approach to address these issues. Greener nanomaterials are synthesized with the principles of green chemistry using environmentally benign and sustainable methods that minimize toxic byproducts, energy consumption, and hazardous waste. Greener nanomaterials facilitate targeted drug delivery and act as scaffolds to encourage cellular attachment, growth, and differentiation to promote the regeneration of particular tissues. Moreover, greener nanomaterials have great potential to improve the efficacy and biocompatibility of regenerative medicine, addressing toxicity concerns associated with conventional nanomaterials. From a diagnostic perspective, recent studies have demonstrated that these materials allow non-intrusive as well as accurate examination of tissue regeneration processes through enhanced imaging techniques like Magnetic Resonance Imaging (MRI), Computed Tomography (CT), along fluorescence-based imaging. These techniques offer improved sensitivity, real-time visualization, and higher biocompatibility when combined with biosynthesized metallic nanoparticles like gold and silver. The present article demonstrates the role and different types of greener nanomaterials in diagnosing and managing soft tissue regeneration. Furthermore, we critically assessed the challenges and clinical translations related to greener nanomaterials.
{"title":"Greener nanomaterials for soft tissue regeneration: Diagnostic and therapeutic advances","authors":"Garima ,&nbsp;Deepika Sharma ,&nbsp;Neeraj Mittal","doi":"10.1016/j.jddst.2025.106747","DOIUrl":"10.1016/j.jddst.2025.106747","url":null,"abstract":"<div><div>Soft tissue injuries and organ dysfunction present significant medical challenges, however, nanotechnology using green chemistry offers a transformative approach to address these issues. Greener nanomaterials are synthesized with the principles of green chemistry using environmentally benign and sustainable methods that minimize toxic byproducts, energy consumption, and hazardous waste. Greener nanomaterials facilitate targeted drug delivery and act as scaffolds to encourage cellular attachment, growth, and differentiation to promote the regeneration of particular tissues. Moreover, greener nanomaterials have great potential to improve the efficacy and biocompatibility of regenerative medicine, addressing toxicity concerns associated with conventional nanomaterials. From a diagnostic perspective, recent studies have demonstrated that these materials allow non-intrusive as well as accurate examination of tissue regeneration processes through enhanced imaging techniques like Magnetic Resonance Imaging (MRI), Computed Tomography (CT), along fluorescence-based imaging. These techniques offer improved sensitivity, real-time visualization, and higher biocompatibility when combined with biosynthesized metallic nanoparticles like gold and silver. The present article demonstrates the role and different types of greener nanomaterials in diagnosing and managing soft tissue regeneration. Furthermore, we critically assessed the challenges and clinical translations related to greener nanomaterials.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106747"},"PeriodicalIF":4.5,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488933","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}
引用次数: 0
Nanocarriers and their integrated microneedle systems-mediated drug delivery for the treatment of moderate-severe dermatological diseases: Recent progress, applications and future perspectives
IF 4.5 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-22 DOI: 10.1016/j.jddst.2025.106748
Mridusmita Das, Rabinarayan Parhi
Dermatological diseases significantly affect patients' quality of life and psychological well-being due to their visible symptoms. Currently, treatment options for these conditions include systemic medications, topical treatments, phototherapy, radiotherapy, chemotherapy, surgical resection, and injections. However, each of these treatments has its limitations. In this context, transdermal drug delivery (TDD) is particularly appealing because it allows for the delivery of drugs to affected tissues, reducing systemic side effects. Unfortunately, the stratum corneum (SC), the outermost layer of the skin, severely hampers drug permeation. Nanocarriers loaded with drugs could offer a promising solution for penetrating this SC barrier due to their small size, ideally less than 100 nm. These nanocarriers can also enhance the solubility, stability and target delivery efficiency of the encapsulated drugs. However, the thickened and highly keratinized skin still acts as a barrier to the permeation of these nanocarriers. To overcome this issue, microneedles (MNs) with micron-sized needles can pierce the SC, enabling drug delivery into the viable epidermis and dermis layers of the skin. Therefore, nanocarrier-integrated MN systems can significantly improve drug targeting while minimizing systemic drug exposure and related side effects. This review discusses the anatomy of the skin, the pathways for drug permeation, and methods to enhance drug delivery through the skin, including both chemical and physical approaches. It specifically focuses on various nanocarriers used in TDD and their application in treating moderate to severe dermatological diseases such as psoriasis, atopic dermatitis, and melanoma. It also examines the current therapies for these conditions, advancements in nanocarrier technologies, their integration with MN systems, and their potential applications, along with the challenges and future directions in this field.
{"title":"Nanocarriers and their integrated microneedle systems-mediated drug delivery for the treatment of moderate-severe dermatological diseases: Recent progress, applications and future perspectives","authors":"Mridusmita Das,&nbsp;Rabinarayan Parhi","doi":"10.1016/j.jddst.2025.106748","DOIUrl":"10.1016/j.jddst.2025.106748","url":null,"abstract":"<div><div>Dermatological diseases significantly affect patients' quality of life and psychological well-being due to their visible symptoms. Currently, treatment options for these conditions include systemic medications, topical treatments, phototherapy, radiotherapy, chemotherapy, surgical resection, and injections. However, each of these treatments has its limitations. In this context, transdermal drug delivery (TDD) is particularly appealing because it allows for the delivery of drugs to affected tissues, reducing systemic side effects. Unfortunately, the stratum corneum (SC), the outermost layer of the skin, severely hampers drug permeation. Nanocarriers loaded with drugs could offer a promising solution for penetrating this SC barrier due to their small size, ideally less than 100 nm. These nanocarriers can also enhance the solubility, stability and target delivery efficiency of the encapsulated drugs. However, the thickened and highly keratinized skin still acts as a barrier to the permeation of these nanocarriers. To overcome this issue, microneedles (MNs) with micron-sized needles can pierce the SC, enabling drug delivery into the viable epidermis and dermis layers of the skin. Therefore, nanocarrier-integrated MN systems can significantly improve drug targeting while minimizing systemic drug exposure and related side effects. This review discusses the anatomy of the skin, the pathways for drug permeation, and methods to enhance drug delivery through the skin, including both chemical and physical approaches. It specifically focuses on various nanocarriers used in TDD and their application in treating moderate to severe dermatological diseases such as psoriasis, atopic dermatitis, and melanoma. It also examines the current therapies for these conditions, advancements in nanocarrier technologies, their integration with MN systems, and their potential applications, along with the challenges and future directions in this field.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106748"},"PeriodicalIF":4.5,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478982","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}
引用次数: 0
Microgels of alginate dialdehyde with WGA lectin conjugate for curcumin encapsulation
IF 4.5 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-21 DOI: 10.1016/j.jddst.2025.106717
Arlina Prima Putri , Marissa Angelina , Mochamad Chalid , Francesco Picchioni , Hero Jan Heeres
Wheat germ agglutinin (WGA) is a plant-lectin that is potentially attractive to be used in the formulation of drug delivery systems. In this study, we report the synthesis and use of this lectin in a microgel formulation together with a modified alginate for drug delivery purposes. The alginate used in the formulation was obtained by oxidation of Na-alginate and contains reactive aldehyde groups (ADA). These aldehyde groups are essential and able to form a conjugate with lectin (ADAWGA) using a reductive amination protocol. 1H NMR, DOSY, and ATR-FTIR were performed to characterize ADAWGA and confirm that the reaction is successful. Microgels based on ADAWGA were prepared by a micro emulsion technique utilizing calcium chloride as a crosslinking agent. For comparison, microgels with only the alginate and alginates in combination with ADA were also prepared. Microgels with average particle sizes ranging from 285 to 529 nm were obtained. The microgels were loaded with curcumin, a hydrophobic natural polyphenol, and the release pattern was investigated. The result of the release profiles from the curcumin-loaded microgels shown that the profile was fit the Higuchi model, whit the R2 values range from 0.90 to 0.98. Cytotoxicity studies revealed that the microgels exhibit low toxicity toward the MCF-7 cells at low concentrations, making them suitable for drug delivery application.
{"title":"Microgels of alginate dialdehyde with WGA lectin conjugate for curcumin encapsulation","authors":"Arlina Prima Putri ,&nbsp;Marissa Angelina ,&nbsp;Mochamad Chalid ,&nbsp;Francesco Picchioni ,&nbsp;Hero Jan Heeres","doi":"10.1016/j.jddst.2025.106717","DOIUrl":"10.1016/j.jddst.2025.106717","url":null,"abstract":"<div><div>Wheat germ agglutinin (WGA) is a plant-lectin that is potentially attractive to be used in the formulation of drug delivery systems. In this study, we report the synthesis and use of this lectin in a microgel formulation together with a modified alginate for drug delivery purposes. The alginate used in the formulation was obtained by oxidation of Na-alginate and contains reactive aldehyde groups (ADA). These aldehyde groups are essential and able to form a conjugate with lectin (ADAWGA) using a reductive amination protocol. <sup>1</sup>H NMR, DOSY, and ATR-FTIR were performed to characterize ADAWGA and confirm that the reaction is successful. Microgels based on ADAWGA were prepared by a micro emulsion technique utilizing calcium chloride as a crosslinking agent. For comparison, microgels with only the alginate and alginates in combination with ADA were also prepared. Microgels with average particle sizes ranging from 285 to 529 nm were obtained. The microgels were loaded with curcumin, a hydrophobic natural polyphenol, and the release pattern was investigated. The result of the release profiles from the curcumin-loaded microgels shown that the profile was fit the Higuchi model, whit the <em>R</em><sup>2</sup> values range from 0.90 to 0.98. Cytotoxicity studies revealed that the microgels exhibit low toxicity toward the MCF-7 cells at low concentrations, making them suitable for drug delivery application.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106717"},"PeriodicalIF":4.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520596","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}
引用次数: 0
Nanoemulsion based on Calotropis procera seed oil to delivery of betulinic acid: In vitro release kinetics, in vivo toxicity and MTT assay in PC3 cells 基于石菖蒲籽油的纳米乳液用于递送白桦脂酸:体外释放动力学、体内毒性和 PC3 细胞 MTT 试验
IF 4.5 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-21 DOI: 10.1016/j.jddst.2025.106746
André L.N. de Sousa , Louhana M. Rebouças , Francisco M.F. Lemos , Ana C.B. Ribeiro , Fernando E.T. Cunha , Cláudia Pessoa , Sarah L.A. Sales , Larissa M.R. Silva , Nágila M.P.S. Ricardo
The objective of this work was to obtain a nanoemulsion based on Calotropis procera oil and betulinic acid, for antitumor applications. The nanoemulsion showed high betulinic acid carrying capacity (7500 μg g−1), thermodynamic stability and high Encapsulation Efficiency (>99.98 %). In vitro cytotoxicity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (72 h) against PC3 (prostate cancer) and L929 (fibroblasts). In vivo tests were carried out in a zebrafish model, revealing that the nanoemulsion did not alter locomotor activity and was not toxic within 96 h of oral administration, suggesting its biological safety. The IC50 values for the obtained nanoemulsions ranged from 4.6 to 6.2 μg mL−1 (PC3) and >75 μg mL−1 for fibroblasts. In the 72 h in vitro release tests, it presented controlled release by the Higuchi model, releasing 31.33 % (622.80 μg) of betulinic acid in a controlled manner, representing a possible promising formulation for antitumor applications.
{"title":"Nanoemulsion based on Calotropis procera seed oil to delivery of betulinic acid: In vitro release kinetics, in vivo toxicity and MTT assay in PC3 cells","authors":"André L.N. de Sousa ,&nbsp;Louhana M. Rebouças ,&nbsp;Francisco M.F. Lemos ,&nbsp;Ana C.B. Ribeiro ,&nbsp;Fernando E.T. Cunha ,&nbsp;Cláudia Pessoa ,&nbsp;Sarah L.A. Sales ,&nbsp;Larissa M.R. Silva ,&nbsp;Nágila M.P.S. Ricardo","doi":"10.1016/j.jddst.2025.106746","DOIUrl":"10.1016/j.jddst.2025.106746","url":null,"abstract":"<div><div>The objective of this work was to obtain a nanoemulsion based on <em>Calotropis procera</em> oil and betulinic acid, for antitumor applications. The nanoemulsion showed high betulinic acid carrying capacity (7500 μg g<sup>−1</sup>), thermodynamic stability and high Encapsulation Efficiency (&gt;99.98 %). <em>In vitro</em> cytotoxicity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (72 h) against PC3 (prostate cancer) and L929 (fibroblasts). <em>In vivo</em> tests were carried out in a zebrafish model, revealing that the nanoemulsion did not alter locomotor activity and was not toxic within 96 h of oral administration, suggesting its biological safety. The IC<sub>50</sub> values for the obtained nanoemulsions ranged from 4.6 to 6.2 μg mL<sup>−1</sup> (PC3) and &gt;75 μg mL<sup>−1</sup> for fibroblasts. In the 72 h <em>in vitro</em> release tests, it presented controlled release by the Higuchi model, releasing 31.33 % (622.80 μg) of betulinic acid in a controlled manner, representing a possible promising formulation for antitumor applications.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106746"},"PeriodicalIF":4.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520595","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}
引用次数: 0
Fertile ground for homeostatic reformation: Engineered release platforms for enhanced regenerative outcomes
IF 4.5 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-21 DOI: 10.1016/j.jddst.2025.106740
Pei Wang , Yan Gong , Xiansong Wang , Xiaoxi Lin
Homeostasis is essential for tissue function, highlighting the need for homeostatic reformation (HRF) of the local microenvironment after a lesion. In tissue engineering and regenerative medicine, engineered release platforms (ERPs) are pivotal for the localized and controlled delivery of therapeutic agents, including pharmaceutical drugs and cytokines, to facilitate HRF. However, traditional topical or oral administration often suffer from low drug utilization and inadequate release profiles for sustained therapeutic effects. By utilizing various materials and techniques, ERPs can be tailored to the specific pathological environment and healing needs of targeted tissues, enhancing both the efficacy and duration of therapeutic interventions. This review categorizes ERPs based on their drug release profiles: short-term drug release, long-term drug release, and passive or initiative stimulus-responsive drug release. It provides an overview of current advancements, identifies key limitations, and discusses future directions for the development of ERPs in tissue engineering and regenerative medicine for better HRF.
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引用次数: 0
Navigating COVID-19: Advancements in therapeutics and viral filtration technologies for Today's challenges and tomorrow's solutions
IF 4.5 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-21 DOI: 10.1016/j.jddst.2025.106741
Devesh Kapoor , Bhavna Kumar , Manmohan Singhal , Faiza Himasa Idris , Sonam M. Gandhi , Sankha Bhattachrya , Bhupendra G. Prajapati , Rahul Maheshwari
The COVID-19 pandemic has driven global efforts to develop effective therapeutics and virus filtration technologies to combat SARS-CoV-2 and mitigate its impact on public health. This review focuses on key advancements and emerging trends in these areas, aiming to provide a clear and cohesive narrative that captures the essence of ongoing progress. We begin by establishing a foundational understanding of SARS-CoV-2, exploring its protein structure, pathophysiology, and virology. This knowledge sets the stage for discussing targeted intervention strategies. In the realm of virus filtration technologies, we highlight significant advancements, such as electrostatic-charged nanofiber filters, cytosorb filters, and hypertonic salt solutions. These technologies have demonstrated the potential to mitigate virus transmission and enhance protective measures. Turning to therapeutics, we emphasize innovative approaches that have emerged in response to the pandemic. Key advancements include bioengineering-inspired neutralizing antibodies, immuno-nanomedicines, and the development of anti-COVID drugs, such as spike and protease inhibitors. Artificial intelligence-based peptides and 3-D printing-inspired materials represent additional breakthroughs shaping the future of antiviral therapies. Furthermore, we explore promising emerging trends that complement these efforts. These include cold spray technologies, herbal immune boosters, nanoparticle-based approaches, and antiviral coatings. Such innovations offer exciting prospects for enhancing our preparedness against viral threats. In conclusion, this review underscores the importance of a multidisciplinary approach that integrates advancements in therapeutics and virus filtration technologies. We aim to strengthen global resilience against COVID-19 and future pandemics by focusing on these primary themes, safeguarding public health and well-being.
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引用次数: 0
A novel aminohydroxy sulfonamide formulated in PEGylated liposomes with potential antitumor activity
IF 4.5 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-20 DOI: 10.1016/j.jddst.2025.106739
Carla Caddeo , Ilaria Nigro , Lucia Chiummiento , Maria Funicello , Paolo Lupattelli , Alessandro Santarsiere , Xavier Fernàndez-Busquets , Donatella Valenti , Emanuele Rosa , Rocchina Miglionico , Maria Francesca Armentano , Antonio Vassallo
Cancer ranks as a leading cause of death worldwide, with liver cancer being one of the most commonly diagnosed. Currently, several molecules are being studied in order to find new therapeutic options that can reduce cancer recurrence rate and increase patient survival. This study proposes PEGylated liposomes for the delivery of a newly synthesized aminohydroxy sulfonamide, BupM-NH2, which has shown dose-dependent cytotoxicity towards hepatic tumor cells. The prepared PEG-liposomes were nanosized, spherical, and unilamellar, as shown by light scattering data and cryo-TEM micrographs. The physical stability of the PEG-liposomes was preserved when tested in simulated body fluids. Similar results were found for the storage stability evaluation. Furthermore, the PEG-liposomes efficiently entrapped BupM-NH2 and modulated its release. The antitumor activity of BupM-NH2 in PEG-liposomes was assessed in vitro in hepatocarcinoma cells. The viability assay showed that PEG-liposomes were able to control the release of BupM-NH2 over time and induce the death of HepG2 cells at a concentration about two-times lower than that required by free BupM-NH2 (IC50: 33.31 vs. 57.05 μM). Furthermore, the liposomal formulation showed a less cytotoxic effect against non-cancerous cell line (IHH) compared to the free molecule (IC50 > 200 vs. 106.9 μM), encouraging further investigation to confirm its effective and safe use.
{"title":"A novel aminohydroxy sulfonamide formulated in PEGylated liposomes with potential antitumor activity","authors":"Carla Caddeo ,&nbsp;Ilaria Nigro ,&nbsp;Lucia Chiummiento ,&nbsp;Maria Funicello ,&nbsp;Paolo Lupattelli ,&nbsp;Alessandro Santarsiere ,&nbsp;Xavier Fernàndez-Busquets ,&nbsp;Donatella Valenti ,&nbsp;Emanuele Rosa ,&nbsp;Rocchina Miglionico ,&nbsp;Maria Francesca Armentano ,&nbsp;Antonio Vassallo","doi":"10.1016/j.jddst.2025.106739","DOIUrl":"10.1016/j.jddst.2025.106739","url":null,"abstract":"<div><div>Cancer ranks as a leading cause of death worldwide, with liver cancer being one of the most commonly diagnosed. Currently, several molecules are being studied in order to find new therapeutic options that can reduce cancer recurrence rate and increase patient survival. This study proposes PEGylated liposomes for the delivery of a newly synthesized aminohydroxy sulfonamide, BupM-NH<sub>2</sub>, which has shown dose-dependent cytotoxicity towards hepatic tumor cells. The prepared PEG-liposomes were nanosized, spherical, and unilamellar, as shown by light scattering data and cryo-TEM micrographs. The physical stability of the PEG-liposomes was preserved when tested in simulated body fluids. Similar results were found for the storage stability evaluation. Furthermore, the PEG-liposomes efficiently entrapped BupM-NH<sub>2</sub> and modulated its release. The antitumor activity of BupM-NH<sub>2</sub> in PEG-liposomes was assessed <em>in vitro</em> in hepatocarcinoma cells. The viability assay showed that PEG-liposomes were able to control the release of BupM-NH<sub>2</sub> over time and induce the death of HepG2 cells at a concentration about two-times lower than that required by free BupM-NH<sub>2</sub> (IC<sub>50</sub>: 33.31 <em>vs.</em> 57.05 μM). Furthermore, the liposomal formulation showed a less cytotoxic effect against non-cancerous cell line (IHH) compared to the free molecule (IC<sub>50</sub> &gt; 200 <em>vs.</em> 106.9 μM), encouraging further investigation to confirm its effective and safe use.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106739"},"PeriodicalIF":4.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of Drug Delivery Science and Technology
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