Pub Date : 2025-02-21DOI: 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 , 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","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 (>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 >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}
Pub Date : 2025-02-21DOI: 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.
{"title":"Fertile ground for homeostatic reformation: Engineered release platforms for enhanced regenerative outcomes","authors":"Pei Wang , Yan Gong , Xiansong Wang , Xiaoxi Lin","doi":"10.1016/j.jddst.2025.106740","DOIUrl":"10.1016/j.jddst.2025.106740","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106740"},"PeriodicalIF":4.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510097","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}
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.
{"title":"Navigating COVID-19: Advancements in therapeutics and viral filtration technologies for Today's challenges and tomorrow's solutions","authors":"Devesh Kapoor , Bhavna Kumar , Manmohan Singhal , Faiza Himasa Idris , Sonam M. Gandhi , Sankha Bhattachrya , Bhupendra G. Prajapati , Rahul Maheshwari","doi":"10.1016/j.jddst.2025.106741","DOIUrl":"10.1016/j.jddst.2025.106741","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106741"},"PeriodicalIF":4.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489049","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 : 2025-02-20DOI: 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 , Ilaria Nigro , Lucia Chiummiento , Maria Funicello , Paolo Lupattelli , Alessandro Santarsiere , Xavier Fernàndez-Busquets , Donatella Valenti , Emanuele Rosa , Rocchina Miglionico , Maria Francesca Armentano , 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> > 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}
Pub Date : 2025-02-20DOI: 10.1016/j.jddst.2025.106704
He Zhang , Jiarui Chen , Xiaolu Han , Liang Xu , Zengming Wang , Nan Liu , Yang Yang , Hui Zhang , Ai-ping Zheng
Needle-Free Injection Technology (NFIT), which administers medication through a high-pressure transdermal jet, is limited to a delivery volume of no more than 1 mL due to device constraints. This poses challenges for the administration of poorly water-soluble drugs. Despite its potential for intramuscular delivery of nanocrystal drugs, research in this area is scarce, particularly regarding the exploration of the injection process and outcomes at the intramuscular depth. We developed solution and nanosuspension formulations of the poorly water-soluble drug midazolam and assessing their effectiveness following NFIT and needle injection administration. Our systematic evaluations encompass the velocity of needle-free injection, the establishment of a gel model for visualizing distribution, and documentation of the needle-free injection process, distribution range, impact of needle-free injection on nanocrystals’ size and tissue injury, as well as a comprehensive pharmacokinetic study. Our systematic evaluation confirmed that the nanocrystals retained their physicochemical properties following needle-free injection, ensuring consistent therapeutic efficacy. A significant finding was the faster time to maximum concentration (Tmax) observed with the NFIT-administered nanosuspension (11.67 ± 5.16 min) compared to both the needle injection of nanosuspension (32.50 ± 22.08 min) and the NFIT-administered solution (32.50 ± 14.75 min). Additionally, the needle-free method extended the residence time of the nanosuspension formulation. This research enhanced our understanding of NFIT and underscored its synergistic potential when combined with nanosuspensions for intramuscular drug delivery. Our findings present NFIT as a viable, less injury and rapidly effective alternative to traditional needle injections, especially offering a promising approach for the administration of midazolam nanosuspension.
{"title":"A comprehensive study on needle-free injection technology combined with midazolam nanosuspension","authors":"He Zhang , Jiarui Chen , Xiaolu Han , Liang Xu , Zengming Wang , Nan Liu , Yang Yang , Hui Zhang , Ai-ping Zheng","doi":"10.1016/j.jddst.2025.106704","DOIUrl":"10.1016/j.jddst.2025.106704","url":null,"abstract":"<div><div>Needle-Free Injection Technology (NFIT), which administers medication through a high-pressure transdermal jet, is limited to a delivery volume of no more than 1 mL due to device constraints. This poses challenges for the administration of poorly water-soluble drugs. Despite its potential for intramuscular delivery of nanocrystal drugs, research in this area is scarce, particularly regarding the exploration of the injection process and outcomes at the intramuscular depth. We developed solution and nanosuspension formulations of the poorly water-soluble drug midazolam and assessing their effectiveness following NFIT and needle injection administration. Our systematic evaluations encompass the velocity of needle-free injection, the establishment of a gel model for visualizing distribution, and documentation of the needle-free injection process, distribution range, impact of needle-free injection on nanocrystals’ size and tissue injury, as well as a comprehensive pharmacokinetic study. Our systematic evaluation confirmed that the nanocrystals retained their physicochemical properties following needle-free injection, ensuring consistent therapeutic efficacy. A significant finding was the faster time to maximum concentration (T<sub>max</sub>) observed with the NFIT-administered nanosuspension (11.67 ± 5.16 min) compared to both the needle injection of nanosuspension (32.50 ± 22.08 min) and the NFIT-administered solution (32.50 ± 14.75 min). Additionally, the needle-free method extended the residence time of the nanosuspension formulation. This research enhanced our understanding of NFIT and underscored its synergistic potential when combined with nanosuspensions for intramuscular drug delivery. Our findings present NFIT as a viable, less injury and rapidly effective alternative to traditional needle injections, especially offering a promising approach for the administration of midazolam nanosuspension.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106704"},"PeriodicalIF":4.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471601","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 : 2025-02-19DOI: 10.1016/j.jddst.2025.106731
Siddharth Singh, Rajendra Awasthi
Psoriasis is a multifactorial autoimmune disease characterized by excessive proliferation of keratinocytes. This excessive proliferation led to the formation of plaque with itching and silvery patches. The transferosome-loaded hydrogel was developed using a 1 % hyaluronic acid gel base and subjected to in vitro (pH, rheology, spreadability, and in vitro release studies) and in vivo evaluation. The imiquimod-induced psoriatic mice model was developed for the determination of anti-psoriatic activity of the transferosome-loaded hydrogel formulation. The transferosomal hydrogel formulation was found to be homogenous with a pH of 5.4 ± 0.4, which is acceptable for topical delivery. The transferosomal hydrogel exhibited pseudoplastic behavior that is acceptable for dermatological therapy with 9.8 g cm sec−1 spreadability. It was found that diacerein released 88.44 ± 2.11 % and berberine HCl released 81.56 ± 0.11 % over 24 h, showing a sustained release profile. In the psoriatic BALB/c mice model, berberine HCl and diacerein-loaded transferosomes containing hydrogel formulation (BDTG transferosomal gel) reduced erythema and scaling. The skin histology depicted an alleviation of epidermal thickness and reduced acanthosis. ELISA assay confirmed that the hydrogel formulation reduced inflammation by minimizing TNF-α and IL-17A levels. Thus, co-delivery of diacerein and berberine HCl in lipid-based nanocarriers has effective therapeutic outcomes in psoriatic animals due to the improved skin penetration and prolonged local residence time. However, the future scope necessitates clinical studies of the developed formulation to prove its anti-psoriatic activity.
{"title":"Topical transferosomal gel of berberine HCl and diacerein reduced TNF-α and IL-17A levels and reduced epidermal thickness in imiquimod-induced psoriatic BALB/c mice","authors":"Siddharth Singh, Rajendra Awasthi","doi":"10.1016/j.jddst.2025.106731","DOIUrl":"10.1016/j.jddst.2025.106731","url":null,"abstract":"<div><div>Psoriasis is a multifactorial autoimmune disease characterized by excessive proliferation of keratinocytes. This excessive proliferation led to the formation of plaque with itching and silvery patches. The transferosome-loaded hydrogel was developed using a 1 % hyaluronic acid gel base and subjected to <em>in vitro</em> (pH, rheology, spreadability, and <em>in vitro</em> release studies) and <em>in vivo</em> evaluation. The imiquimod-induced psoriatic mice model was developed for the determination of anti-psoriatic activity of the transferosome-loaded hydrogel formulation. The transferosomal hydrogel formulation was found to be homogenous with a pH of 5.4 ± 0.4, which is acceptable for topical delivery. The transferosomal hydrogel exhibited pseudoplastic behavior that is acceptable for dermatological therapy with 9.8 g cm sec<sup>−1</sup> spreadability. It was found that diacerein released 88.44 ± 2.11 % and berberine HCl released 81.56 ± 0.11 % over 24 h, showing a sustained release profile. In the psoriatic BALB/c mice model, berberine HCl and diacerein-loaded transferosomes containing hydrogel formulation (BDTG transferosomal gel) reduced erythema and scaling. The skin histology depicted an alleviation of epidermal thickness and reduced acanthosis. ELISA assay confirmed that the hydrogel formulation reduced inflammation by minimizing TNF-α and IL-17A levels. Thus, co-delivery of diacerein and berberine HCl in lipid-based nanocarriers has effective therapeutic outcomes in psoriatic animals due to the improved skin penetration and prolonged local residence time. However, the future scope necessitates clinical studies of the developed formulation to prove its anti-psoriatic activity.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106731"},"PeriodicalIF":4.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471598","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 : 2025-02-19DOI: 10.1016/j.jddst.2025.106714
Rehan Ullah , Chia-Yi Tseng , Aziz ur Rahman , Sarwar Allah Ditta , Atif Yaqub , Sohail Akhtar , Dil naz , Ali Muhammad , Muhammad Rashid , Basit Ali Khan , Asad Ullah
Nanoparticles (NPs) are colloidal particles ranging in size from 1 to 100 nm. They consist of a variety of various materials including metals, polymers, lipids and phospholipids. NPs exhibit unique physical and chemical properties due to the size and high surface area to volume ratio relative to their bulk material. Silver is one of the oldest metals used as an antimicrobial, antioxidant, and antiseptic. Silver was traditionally used in bulk, but nanotechnology has allowed us to save our precious metal resources. We can use a minute dose of the same metal with the best results in the form of nanoparticles. Green synthesis methods are being processed to harvest all the benefits of silver and avoid its inimical effects. Plant extracts or microbes are used as reducing and stabilizing agents. This study also attempts to synthesize silver nanoparticles using Sedum adenotrichum extract and evaluate their antioxidant activity. High potential liquid chromatography (HPLC) was performed for elemental analysis and Sedum adenotrichum synthesized silver nanoparticles (S.AgNPs) were characterized by UV–Vis spectroscopy and FTIR. Synthesized nanoparticles' in vitro antioxidant potential were evaluated. For in vivo antioxidant analysis, twenty-five albino mice were randomly divided into five groups. Each treatment group received doses at 20, 30 and 40 mg per body weight according to their group. DPPH and FRP activities of S.AgNPs 24.03 % and 0.21 % were greater than chemically synthesized silver nanoparticles (C.AgNPs) 7.25 % and 0.11 % respectively. In vivo, the antioxidant activity of S.AgNPs was also significantly different (p < 0.05) when compared with C.AgNPs. In conclusion, S.AgNPs are eco-friendly, efficient, and more powerful antioxidants.
{"title":"Synthesis of silver nanoparticles by Sedum adenotrichum extract and evaluating their antioxidant potential in albino mice","authors":"Rehan Ullah , Chia-Yi Tseng , Aziz ur Rahman , Sarwar Allah Ditta , Atif Yaqub , Sohail Akhtar , Dil naz , Ali Muhammad , Muhammad Rashid , Basit Ali Khan , Asad Ullah","doi":"10.1016/j.jddst.2025.106714","DOIUrl":"10.1016/j.jddst.2025.106714","url":null,"abstract":"<div><div>Nanoparticles (NPs) are colloidal particles ranging in size from 1 to 100 nm. They consist of a variety of various materials including metals, polymers, lipids and phospholipids. NPs exhibit unique physical and chemical properties due to the size and high surface area to volume ratio relative to their bulk material. Silver is one of the oldest metals used as an antimicrobial, antioxidant, and antiseptic. Silver was traditionally used in bulk, but nanotechnology has allowed us to save our precious metal resources. We can use a minute dose of the same metal with the best results in the form of nanoparticles. Green synthesis methods are being processed to harvest all the benefits of silver and avoid its inimical effects. Plant extracts or microbes are used as reducing and stabilizing agents. This study also attempts to synthesize silver nanoparticles using <em>Sedum adenotrichum</em> extract and evaluate their antioxidant activity. High potential liquid chromatography (HPLC) was performed for elemental analysis and <em>Sedum adenotrichum</em> synthesized silver nanoparticles (S.AgNPs) were characterized by UV–Vis spectroscopy and FTIR. Synthesized nanoparticles' in vitro antioxidant potential were evaluated. For in vivo antioxidant analysis, twenty-five albino mice were randomly divided into five groups. Each treatment group received doses at 20, 30 and 40 mg per body weight according to their group. DPPH and FRP activities of S.AgNPs 24.03 % and 0.21 % were greater than chemically synthesized silver nanoparticles (C.AgNPs) 7.25 % and 0.11 % respectively. <em>In vivo,</em> the antioxidant activity of S.AgNPs was also significantly different (p < 0.05) when compared with C.AgNPs. In conclusion, S.AgNPs are eco-friendly, efficient, and more powerful antioxidants.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106714"},"PeriodicalIF":4.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510098","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 : 2025-02-19DOI: 10.1016/j.jddst.2025.106726
Manasi Kale, Sharvil Patil, Ravindra Kamble
Tadalafil (TDF) is a Biopharmaceutics Classification System (BCS) class II drug representing low aqueous solubility and poor permeability which limits its oral bioavailability. This study used sonoprecipitation process to develop chitosan-coated tadalafil nanocrystals (CS-TNC). Box-Behnken design (BBD) was used for optimization of CS-TNC and was investigated regarding stabilizer concentration, chitosan concentration, and sonication time. The optimized CS-coated nanocrystals showed rod-shaped particles with an average size, zeta potential, and entrapment efficiency of 263.41 ± 4.11 nm, −34.32 ± 1.34 mV, and 90.88 ± 5.33 %. The crystal form and chemical structure of CS-TNC did not alter throughout the procedure, as per the results of differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD), and fourier transform infrared spectroscopy (FT-IR) when compared to TDF dispersion and tadalafil nanocrystals without chitosan (TNC). Apparent permeability coefficient (Papp) of CS-TNC increased by 6.0-, 6.7-, and 7.4-folds, respectively, in the duodenum, jejunum, and ileum according to results from the everted gut sac. This suggests that chitosan-coated nanocrystals may improve intestinal absorption of tadalafil by increasing permeability and inhibiting P-gp efflux. In comparison to TNC and TDF, the Cmax of CS-TNC was 3.3 and 5.5 times higher, while the AUC0-t was 2.3 and 6.0 times higher, respectively. The prepared formulation displayed improved aqueous solubility, in vitro release, and superior stability suggesting its utility towards commercial application.
{"title":"Fabrication of chitosan-coated tadalafil nanocrystals by Box-Behnken design to enhance its solubility and oral bioavailability via sonoprecipitation technique","authors":"Manasi Kale, Sharvil Patil, Ravindra Kamble","doi":"10.1016/j.jddst.2025.106726","DOIUrl":"10.1016/j.jddst.2025.106726","url":null,"abstract":"<div><div>Tadalafil (TDF) is a Biopharmaceutics Classification System (BCS) class II drug representing low aqueous solubility and poor permeability which limits its oral bioavailability. This study used sonoprecipitation process to develop chitosan-coated tadalafil nanocrystals (CS-TNC). Box-Behnken design (BBD) was used for optimization of CS-TNC and was investigated regarding stabilizer concentration, chitosan concentration, and sonication time. The optimized CS-coated nanocrystals showed rod-shaped particles with an average size, zeta potential, and entrapment efficiency of 263.41 ± 4.11 nm, −34.32 ± 1.34 mV, and 90.88 ± 5.33 %. The crystal form and chemical structure of CS-TNC did not alter throughout the procedure, as per the results of differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD), and fourier transform infrared spectroscopy (FT-IR) when compared to TDF dispersion and tadalafil nanocrystals without chitosan (TNC). Apparent permeability coefficient (Papp) of CS-TNC increased by 6.0-, 6.7-, and 7.4-folds, respectively, in the duodenum, jejunum, and ileum according to results from the everted gut sac. This suggests that chitosan-coated nanocrystals may improve intestinal absorption of tadalafil by increasing permeability and inhibiting P-gp efflux. In comparison to TNC and TDF, the C<sub>max</sub> of CS-TNC was 3.3 and 5.5 times higher, while the AUC<sub>0-t</sub> was 2.3 and 6.0 times higher, respectively. The prepared formulation displayed improved aqueous solubility, <em>in vitro</em> release, and superior stability suggesting its utility towards commercial application.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106726"},"PeriodicalIF":4.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478989","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 : 2025-02-19DOI: 10.1016/j.jddst.2025.106730
Samideh Khoei , Sepideh Khoee , Elahe Sadri , Fariba Mafakheri , Bahareh Haji Ali , Sakine Shirvalilou
Glioblastoma multiforme (GBM) is highly heterogeneous and poses significant challenges for delivering chemotherapeutic agents, primarily due to barriers like the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB). This study hypothesizes that an alternating magnetic field (AMF) can influence the interaction between magnetic nanoparticles (MNPs) and cells, enhancing drug delivery to the brain as a magnetically guided therapy. We synthesized Janus iron oxide nanoparticles (MJNPs) that are dual conjugated with fluorescein dye (FL) for tracing, folic acid (FA) for active targeting, and doxorubicin (DOX), resulting in the formulation (DOX/MJNPs-FLA). The morphological properties of DOX/MJNPs-FLA were evaluated using various bio-physicochemical methods, including high-resolution transmission electron microscopy (HR-TEM), zeta potential analysis, and dynamic light scattering (DLS). The biosafety and biocompatibility of the nanoparticles were evaluated using the MTT test, hemolytic activity assay, and enzyme level analysis for liver and kidney function. The release of DOX from the nanoparticles was monitored using high-performance liquid chromatography (HPLC) in a rabbit model. Additionally, we evaluated the effect of applying an AMF on the rate at which nanoparticles cross the BBB and their accumulation in tumor cells through fluorescent imaging, Prussian blue staining, and inductively coupled plasma optical emission spectroscopy (ICP-OES). The results demonstrated that bio-safe DOX/MJNPs-FLA nanoparticles, measuring 80 nm, are capable of effective tracking, and sustained DOX release in vivo. Furthermore, drug delivery to the brain was significantly enhanced when a constant magnetic field (MF) and folic acid ligand were employed, indicating an active ligand/receptor mechanism compared to the control (p < 0.01). Continuing the application of the AMF further enhanced the effects of both the MF & FA, resulting in the highest accumulation of nanoparticles in the tumor, as evidenced by ICP-OES results and microscopic imaging. The findings suggest that an AMF can improve the delivery of MNPs across cell barriers and enhance the uptake of nanoparticles into cells and tissues. Moreover, the hyperthermia induced by the AMF activation MJNPs-FLA may increase the permeability of the BBB, potentially improving therapies aimed at diagnosing and treating various brain diseases.
{"title":"Fluorescence-based multimodal imaging for in vivo tracking of magnetite Janus nanoparticles as potential carriers for DOX under the alternating magnetic field: Enhancing tumor penetration","authors":"Samideh Khoei , Sepideh Khoee , Elahe Sadri , Fariba Mafakheri , Bahareh Haji Ali , Sakine Shirvalilou","doi":"10.1016/j.jddst.2025.106730","DOIUrl":"10.1016/j.jddst.2025.106730","url":null,"abstract":"<div><div>Glioblastoma multiforme (GBM) is highly heterogeneous and poses significant challenges for delivering chemotherapeutic agents, primarily due to barriers like the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB). This study hypothesizes that an alternating magnetic field (AMF) can influence the interaction between magnetic nanoparticles (MNPs) and cells, enhancing drug delivery to the brain as a magnetically guided therapy. We synthesized Janus iron oxide nanoparticles (MJNPs) that are dual conjugated with fluorescein dye (FL) for tracing, folic acid (FA) for active targeting, and doxorubicin (DOX), resulting in the formulation (DOX/MJNPs-FLA). The morphological properties of DOX/MJNPs-FLA were evaluated using various bio-physicochemical methods, including high-resolution transmission electron microscopy (HR-TEM), zeta potential analysis, and dynamic light scattering (DLS). The biosafety and biocompatibility of the nanoparticles were evaluated using the MTT test, hemolytic activity assay, and enzyme level analysis for liver and kidney function. The release of DOX from the nanoparticles was monitored using high-performance liquid chromatography (HPLC) in a rabbit model. Additionally, we evaluated the effect of applying an AMF on the rate at which nanoparticles cross the BBB and their accumulation in tumor cells through fluorescent imaging, Prussian blue staining, and inductively coupled plasma optical emission spectroscopy (ICP-OES). The results demonstrated that bio-safe DOX/MJNPs-FLA nanoparticles, measuring 80 nm, are capable of effective tracking, and sustained DOX release in vivo. Furthermore, drug delivery to the brain was significantly enhanced when a constant magnetic field (MF) and folic acid ligand were employed, indicating an active ligand/receptor mechanism compared to the control (p < 0.01). Continuing the application of the AMF further enhanced the effects of both the MF & FA, resulting in the highest accumulation of nanoparticles in the tumor, as evidenced by ICP-OES results and microscopic imaging. The findings suggest that an AMF can improve the delivery of MNPs across cell barriers and enhance the uptake of nanoparticles into cells and tissues. Moreover, the hyperthermia induced by the AMF activation MJNPs-FLA may increase the permeability of the BBB, potentially improving therapies aimed at diagnosing and treating various brain diseases.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106730"},"PeriodicalIF":4.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471602","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 : 2025-02-18DOI: 10.1016/j.jddst.2025.106723
Dalia H. Abdelkader , Samar M. Elshaer , Eman A. Elkordy , Naglaa I. Sarhan , Ebtessam A. Essa
This study investigated pioglitazone hydrochloride (PGZ), an antidiabetic drug, as a wound healing promoter employing the in-situ gel approach. Poloxamer 407 was selected due to its thermo-reversible sol-gel transition properties, in the presence or absence of chitosan. PGZ solubility was enhanced by the solid dispersion (SD) technique, using Hydroxypropyl methylcellulose (HPMC) as a matrix former. SDs increased PGZ solubility up to 3.3-fold due to increased drug wettability and modulated drug crystallinity as reflected from thermal analysis. In-situ gel systems, loaded with optimized SD, were prepared at 14–20%w/v of Poloxamer-407. Chitosan (0.5%w/v) was added to some formulations. In-vitro characterization was performed regarding viscosity, pH, gelation temperature, gelation time, and in-vitro release profiles. All formulations displayed a prolonged release pattern, with hybrid polymeric in-situ gel formula F5 showing suitable gelation time (18.8 ± 1.0 s), gelation temperature (33.9 ± 0.1 °C), viscosity value of 1332 ± 1.0 cP (at 34 °C) and a pH of 5.6 ± 0.1. F5 also showed the highest cumulative drug release (47.5 % ± 0.3) over 8 h with acceptable mucoadhesive properties with a tensile strength value of 11.9 ± 1.5 N/mm2. This formulation was stable after one month of storage at 4 °C, room temperature, and accelerated conditions. The wound healing ability of F5 was investigated using Wistar albino rats. The wound contraction was highest in the in-situ gel, compared to PGZ suspension. Histopathological examination (H&E, Masson trichrome, and α SMA) reflected the superiority of the optimized system in restoring the normal architecture of the skin.
{"title":"Pioglitazone repurposing via in-situ gelling system: An effective topical strategy for wound management","authors":"Dalia H. Abdelkader , Samar M. Elshaer , Eman A. Elkordy , Naglaa I. Sarhan , Ebtessam A. Essa","doi":"10.1016/j.jddst.2025.106723","DOIUrl":"10.1016/j.jddst.2025.106723","url":null,"abstract":"<div><div>This study investigated pioglitazone hydrochloride (PGZ), an antidiabetic drug, as a wound healing promoter employing the <em>in-situ</em> gel approach. Poloxamer 407 was selected due to its thermo-reversible sol-gel transition properties, in the presence or absence of chitosan. PGZ solubility was enhanced by the solid dispersion (SD) technique, using Hydroxypropyl methylcellulose (HPMC) as a matrix former. SDs increased PGZ solubility up to 3.3-fold due to increased drug wettability and modulated drug crystallinity as reflected from thermal analysis. <em>In-situ</em> gel systems, loaded with optimized SD, were prepared at 14–20%w/v of Poloxamer-407. Chitosan (0.5%w/v) was added to some formulations. <em>In-vitro</em> characterization was performed regarding viscosity, pH, gelation temperature, gelation time, and <em>in-vitro</em> release profiles. All formulations displayed a prolonged release pattern, with hybrid polymeric <em>in-situ</em> gel formula F5 showing suitable gelation time (18.8 ± 1.0 s), gelation temperature (33.9 ± 0.1 °C)<strong>,</strong> viscosity value of 1332 ± 1.0 cP (at 34 °C) and a pH of 5.6 ± 0.1. F5 also showed the highest cumulative drug release (47.5 % ± 0.3) over 8 h with acceptable mucoadhesive properties with a tensile strength value of 11.9 ± 1.5 N/mm<sup>2</sup>. This formulation was stable after one month of storage at 4 °C, room temperature, and accelerated conditions. The wound healing ability of F5 was investigated using Wistar albino rats. The wound contraction was highest in the <em>in-situ</em> gel, compared to PGZ suspension. Histopathological examination (H&E, Masson trichrome, and α SMA) reflected the superiority of the optimized system in restoring the normal architecture of the skin.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"106 ","pages":"Article 106723"},"PeriodicalIF":4.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479035","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}