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Disulfiram-Loaded PLGA nanoparticles modified with a Phenyl borate chitosan Conjugate enhance hepatic carcinoma treatment
IF 5.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-27 DOI: 10.1016/j.ijpharm.2025.125293
Yanyi Feng , Hongyu Chen , Simiao Chen , Kaijun Zhang , Dan Yun , Dengyuan Liu , Jinxin Zeng , Chutong Yang , Qingchun Xie
Disulfiram (DSF), which has been traditionally used to treat alcoholism, has been shown to inhibit tumor growth, indicating its potential as an anticancer agent. However, its development and application are hindered by its poor water solubility, instability in physiological environments, and low bioavailability. In this study, phenylboronic acid-chitosan (PBA-CS) grafts were synthesized using the carbodiimide method. PBA-CS-modified DSF PLGA nanoparticles (DSF@PBA-CS-PLGA NPs) were constructed by coating the nanoparticle surfaces with PBA-CS to improve the stability of DSF in physiological environments and enhance its anti-tumor effects. The structures of PBA-CS and the DSF@PBA-CS–PLGA NPs were confirmed using FTIR UVs, DLS, ELS, TEM, 1HNMR, DSC. Our in vitro degradation experiments showed that PBA-CS-PLGA NPs significantly improved the stability of DSF in physiological environments. Cell experiments showed that PBA-CS–PLGA NPs improved drug uptake and strongly inhibited HepG2 cell migration. A mouse tumor model was established using Dutch H22 cells. DSF@PBA-CS-PLGA NPs showed better tumor-targeting ability than DSF@PLGA NPs, with a tumor inhibition rate of more than 60%, and they induced apoptosis and inhibited neovascularization in mouse tumor tissues. Both the in vitro and in vivo experiments indicated that the DSF@PBA-CS-PLGA NPs overcame the limitations of DSF, improving the dissolution rate and stability of the drug, ultimately offering low toxicity, sustained release, and targeted delivery. These findings demonstrated the potential of DSF@PBA-CS-PLGA NPs for hepatic carcinoma therapy.
{"title":"Disulfiram-Loaded PLGA nanoparticles modified with a Phenyl borate chitosan Conjugate enhance hepatic carcinoma treatment","authors":"Yanyi Feng ,&nbsp;Hongyu Chen ,&nbsp;Simiao Chen ,&nbsp;Kaijun Zhang ,&nbsp;Dan Yun ,&nbsp;Dengyuan Liu ,&nbsp;Jinxin Zeng ,&nbsp;Chutong Yang ,&nbsp;Qingchun Xie","doi":"10.1016/j.ijpharm.2025.125293","DOIUrl":"10.1016/j.ijpharm.2025.125293","url":null,"abstract":"<div><div>Disulfiram (DSF), which has been traditionally used to treat alcoholism, has been shown to inhibit tumor growth, indicating its potential as an anticancer agent. However, its development and application are hindered by its poor water solubility, instability in physiological environments, and low bioavailability. In this study, phenylboronic acid-chitosan (PBA-CS) grafts were synthesized using the carbodiimide method. PBA-CS-modified DSF PLGA nanoparticles (DSF@PBA-CS-PLGA NPs) were constructed by coating the nanoparticle surfaces with PBA-CS to improve the stability of DSF in physiological environments and enhance its anti-tumor effects. The structures of PBA-CS and the DSF@PBA-CS–PLGA NPs were confirmed using FTIR UVs, DLS, ELS, TEM, <sup>1</sup>HNMR, DSC. Our in vitro degradation experiments showed that PBA-CS-PLGA NPs significantly improved the stability of DSF in physiological environments. Cell experiments showed that PBA-CS–PLGA NPs improved drug uptake and strongly inhibited HepG2 cell migration. A mouse tumor model was established using Dutch H22 cells. DSF@PBA-CS-PLGA NPs showed better tumor-targeting ability than DSF@PLGA NPs, with a tumor inhibition rate of more than 60%, and they induced apoptosis and inhibited neovascularization in mouse tumor tissues. Both the in vitro and in vivo experiments indicated that the DSF@PBA-CS-PLGA NPs overcame the limitations of DSF, improving the dissolution rate and stability of the drug, ultimately offering low toxicity, sustained release, and targeted delivery. These findings demonstrated the potential of DSF@PBA-CS-PLGA NPs for hepatic carcinoma therapy.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"671 ","pages":"Article 125293"},"PeriodicalIF":5.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synergistic therapy with celastrol-curcumin multifunctional nanomedicine: Anti-hepatocellular carcinoma and reduced hepatotoxicity
IF 5.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-27 DOI: 10.1016/j.ijpharm.2025.125289
Yushi Liu , Jiawen Song , Yurou Guo , Sihui Li , Minghao Yuan , Jiamei Tang , Yulu Wang , Meifeng Li , Yiping Guo , Li Guo
Hepatocellular carcinoma is one of the leading causes of cancer deaths globally and a key hindrance to extending life expectancy. Celastrol (CEL) demonstrates excellent antitumor activity, but faces challenges like low solubility and a narrow therapeutic window, limiting its clinical application. To address these limitations, drug combinations and nano-delivery systems have emerged as effective solutions. Curcumin (CUR), known for its antitumor and hepatoprotective effects, also exhibits good biocompatibility and the ability to mitigate drug-induced liver injury. Considering the complementary properties of CEL and CUR, including CEL’s potent antitumor activity and CUR’s hepatoprotective effects, we developed a novel self-assembling nanodrug delivery system (CCPN) for the co-loading of both compounds. CCPN nanoparticles were constructed through non-covalent interactions, including hydrogen bonding, π-π stacking, and electrostatic forces, which confer good stability and significantly enhance the solubility and bioavailability of CEL and CUR. Extensive in vitro and in vivo experiments demonstrated that CCPN effectively reduced CEL-induced hepatotoxicity in zebrafish and mouse models, exhibiting good biosafety. Additionally, CUR’s fluorescence provides a unique advantage for real-time monitoring of drug distribution and release, facilitating the tracking of therapeutic progress. Furthermore, CCPN nanoparticles enhanced delivery efficiency in HepG2 cells, exhibiting superior anti-liver tumor outcomes, which are associated with the promotion of apoptosis in tumor cells. This study presents CCPN as a promising therapeutic strategy for hepatocellular carcinoma, integrating reduced hepatotoxicity, self-monitoring capabilities, and superior therapeutic efficacy.
{"title":"Synergistic therapy with celastrol-curcumin multifunctional nanomedicine: Anti-hepatocellular carcinoma and reduced hepatotoxicity","authors":"Yushi Liu ,&nbsp;Jiawen Song ,&nbsp;Yurou Guo ,&nbsp;Sihui Li ,&nbsp;Minghao Yuan ,&nbsp;Jiamei Tang ,&nbsp;Yulu Wang ,&nbsp;Meifeng Li ,&nbsp;Yiping Guo ,&nbsp;Li Guo","doi":"10.1016/j.ijpharm.2025.125289","DOIUrl":"10.1016/j.ijpharm.2025.125289","url":null,"abstract":"<div><div>Hepatocellular carcinoma is one of the leading causes of cancer deaths globally and a key hindrance to extending life expectancy. Celastrol (CEL) demonstrates excellent antitumor activity, but faces challenges like low solubility and a narrow therapeutic window, limiting its clinical application. To address these limitations, drug combinations and nano-delivery systems have emerged as effective solutions. Curcumin (CUR), known for its antitumor and hepatoprotective effects, also exhibits good biocompatibility and the ability to mitigate drug-induced liver injury. Considering the complementary properties of CEL and CUR, including CEL’s potent antitumor activity and CUR’s hepatoprotective effects, we developed a novel self-assembling nanodrug delivery system (CCPN) for the co-loading of both compounds. CCPN nanoparticles were constructed through non-covalent interactions, including hydrogen bonding, π-π stacking, and electrostatic forces, which confer good stability and significantly enhance the solubility and bioavailability of CEL and CUR. Extensive <em>in vitro</em> and <em>in vivo</em> experiments demonstrated that CCPN effectively reduced CEL-induced hepatotoxicity in zebrafish and mouse models, exhibiting good biosafety. Additionally, CUR’s fluorescence provides a unique advantage for real-time monitoring of drug distribution and release, facilitating the tracking of therapeutic progress. Furthermore, CCPN nanoparticles enhanced delivery efficiency in HepG2 cells, exhibiting superior anti-liver tumor outcomes, which are associated with the promotion of apoptosis in tumor cells. This study presents CCPN as a promising therapeutic strategy for hepatocellular carcinoma, integrating reduced hepatotoxicity, self-monitoring capabilities, and superior therapeutic efficacy.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"671 ","pages":"Article 125289"},"PeriodicalIF":5.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deep eutectic solvents in analysis, delivery and chemistry of pharmaceuticals.
IF 5.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-26 DOI: 10.1016/j.ijpharm.2025.125278
Saurabh B Ganorkar, Pranay M Hadole, Mangesh R Patil, Chandrakantsing V Pardeshi, Preeti S Bobade, Atul Awe Shirkhedkar, Yvan Vander Heyden

Deep eutectic solvents (DES) have an emerging scientific role, assisting modern pharmaceutics. They are uniquely supporting the resolution of crucial issues, such as the effective extraction and isolation of bio-actives. They act as media and catalysts for pharmaceutical drug synthesis, and as green solvents and modifiers in pharmaceutical analysis. Their role in pharmaceutical formulation and drug delivery is also up-and-coming, for instance, as alternative drug-solubilizing agents, drug stabilizers and functional additives, as therapeutic deep eutectic solvents, deep eutectic API, and monomers and reaction media for the synthesis of biomaterials for advanced drug delivery. The DES also help transforming medicinal/pharmaceutical chemistry. Although DES were described in 1918, their first pharmaceutical use is only reported in 1960. In view of their broad applicability in pharmaceutics, it may be interesting to review their history, origin, evolution, potential advantages, limitations, and specific applications as green solvents. A chronological and comparative study of the literature showed the important role of DES in green approaches for modern pharmaceuticals. The concepts, applications, and outcomes of DES in pharmaceutical analysis, formulation/drug delivery, and pharmaceutical/medicinal chemistry are presented. A comprehensive outline of the atypical applications of DES as effective green solvents in pharmaceutical bioactive extraction was assessed. Efforts to present classifications of DES explored in pharmaceuticals were also made. The present manuscript also covers computational trend, adds on commercial aspects with potential future applications of DES in pharmaceutical sciences.

{"title":"Deep eutectic solvents in analysis, delivery and chemistry of pharmaceuticals.","authors":"Saurabh B Ganorkar, Pranay M Hadole, Mangesh R Patil, Chandrakantsing V Pardeshi, Preeti S Bobade, Atul Awe Shirkhedkar, Yvan Vander Heyden","doi":"10.1016/j.ijpharm.2025.125278","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.125278","url":null,"abstract":"<p><p>Deep eutectic solvents (DES) have an emerging scientific role, assisting modern pharmaceutics. They are uniquely supporting the resolution of crucial issues, such as the effective extraction and isolation of bio-actives. They act as media and catalysts for pharmaceutical drug synthesis, and as green solvents and modifiers in pharmaceutical analysis. Their role in pharmaceutical formulation and drug delivery is also up-and-coming, for instance, as alternative drug-solubilizing agents, drug stabilizers and functional additives, as therapeutic deep eutectic solvents, deep eutectic API, and monomers and reaction media for the synthesis of biomaterials for advanced drug delivery. The DES also help transforming medicinal/pharmaceutical chemistry. Although DES were described in 1918, their first pharmaceutical use is only reported in 1960. In view of their broad applicability in pharmaceutics, it may be interesting to review their history, origin, evolution, potential advantages, limitations, and specific applications as green solvents. A chronological and comparative study of the literature showed the important role of DES in green approaches for modern pharmaceuticals. The concepts, applications, and outcomes of DES in pharmaceutical analysis, formulation/drug delivery, and pharmaceutical/medicinal chemistry are presented. A comprehensive outline of the atypical applications of DES as effective green solvents in pharmaceutical bioactive extraction was assessed. Efforts to present classifications of DES explored in pharmaceuticals were also made. The present manuscript also covers computational trend, adds on commercial aspects with potential future applications of DES in pharmaceutical sciences.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"125278"},"PeriodicalIF":5.3,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In situ generation of Copper sulfide within Poly(lactic-co-glycolic acid): A strategy for Safer photothermal therapy in Triple-Negative breast cancer
IF 5.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-26 DOI: 10.1016/j.ijpharm.2025.125287
Zhenzhen Chen , Lingyan Hu , Bingbing Xu , Zhihong Liu , Lingjun Zeng , Minxin Zhang , Haihong Tian , Hongtao Song
Copper sulfide nanoparticles (CuS NPs) have garnered significant attention in photothermal therapy (PTT) owing to their facile synthesis, biodegradability, stability, and excellent photothermal conversion efficiency. Nonetheless, their potential toxic effects have restricted their application. This research focuses on the encapsulation of CuS NPs with the biocompatible polymer poly(lactic-co-glycolic acid) (PLGA) to enhance their biocompatibility, thereby improving the efficacy and safety of PTT in the treatment of triple-negative breast cancer (TNBC). Three distinct methods, namely aqueous phase loading method, oil phase loading method, and “in situ reduction” method were employed to synthesize PLGA-coated CuS (CuS@PLGA) NPs to optimize the encapsulation rate of CuS. Among these, the CuS@PLGA NPs fabricated via the “in situ reduction” method demonstrated the highest encapsulation efficiency for CuS, achieving a rate of (90.4 ± 3.3)%. The resulting CuS@PLGA NPs exhibited high stability, excellent photothermal effect, and good tumor-targeting ability. Moreover, CuS@PLGA NPs demonstrated enhanced anti-tumor efficacy and biocompatibility compared to CuS NPs in both in vitro and in vivo experiments. Consequently, this study offers an effective and safety strategy for PTT treatment of TNBC.
{"title":"In situ generation of Copper sulfide within Poly(lactic-co-glycolic acid): A strategy for Safer photothermal therapy in Triple-Negative breast cancer","authors":"Zhenzhen Chen ,&nbsp;Lingyan Hu ,&nbsp;Bingbing Xu ,&nbsp;Zhihong Liu ,&nbsp;Lingjun Zeng ,&nbsp;Minxin Zhang ,&nbsp;Haihong Tian ,&nbsp;Hongtao Song","doi":"10.1016/j.ijpharm.2025.125287","DOIUrl":"10.1016/j.ijpharm.2025.125287","url":null,"abstract":"<div><div>Copper sulfide nanoparticles (CuS NPs) have garnered significant attention in photothermal therapy (PTT) owing to their facile synthesis, biodegradability, stability, and excellent photothermal conversion efficiency. Nonetheless, their potential toxic effects have restricted their application. This research focuses on the encapsulation of CuS NPs with the biocompatible polymer poly(lactic-co-glycolic acid) (PLGA) to enhance their biocompatibility, thereby improving the efficacy and safety of PTT in the treatment of triple-negative breast cancer (TNBC). Three distinct methods, namely aqueous phase loading method, oil phase loading method, and “<em>in situ</em> reduction” method were employed to synthesize PLGA-coated CuS (CuS@PLGA) NPs to optimize the encapsulation rate of CuS. Among these, the CuS@PLGA NPs fabricated <em>via</em> the “<em>in situ</em> reduction” method demonstrated the highest encapsulation efficiency for CuS, achieving a rate of (90.4 ± 3.3)%. The resulting CuS@PLGA NPs exhibited high stability, excellent photothermal effect, and good tumor-targeting ability. Moreover, CuS@PLGA NPs demonstrated enhanced anti-tumor efficacy and biocompatibility compared to CuS NPs in both <em>in vitro</em> and <em>in vivo</em> experiments. Consequently, this study offers an effective and safety strategy for PTT treatment of TNBC.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"671 ","pages":"Article 125287"},"PeriodicalIF":5.3,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Experimental measurements of particle deposition in the human nasal airway.
IF 5.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-26 DOI: 10.1016/j.ijpharm.2025.125280
Zhiwei Shen, Taye Tolu Mekonnen, Xinyu Cai, Liam Milton-McGurk, Hak-Kim Chan, Agisilaos Kourmatzis, Shaokoon Cheng

Intranasal drug delivery is a promising non-invasive method for administering both local and systemic medications. While previous studies have extensively investigated the effects of particle size, airflow dynamics, and deposition locations on deposition efficiency, they have not focused on the thickness of deposited particles, which can significantly affect drug dissolution, absorption and therapeutic efficacy. This study investigates the deposition patterns of dry powder particles within the nasal airway, specifically examining how factors such as flow rates, particle size, and particle cohesiveness influence deposition patterns and their thickness. Using optical coherence tomography (OCT), this study assessed the deposition behaviour of three different lactose powders in a reconstructed nasal airway model at three key anatomical locations under varying flow rates (15, 35 and 55 L/min). Computational fluid dynamics (CFD) simulations were conducted to complement the experimental data, demonstrating the airflow dynamics in the nasal airway and highlighting recirculation zones that impact deposition patterns. The results revealed that the anterior section of the nasal airway is particularly effective at capturing particles, with localised flow patterns playing a critical role in particle accumulation. These flow patterns, combined with particle size and cohesiveness, are key factors in determining where and how particles cluster, leading to thicker deposition in specific areas of the nasal airway. This study addresses the gap in understanding how these factors influence deposition thickness and spatial distribution, ultimately contributing to the optimisation of nasal drug delivery systems.

{"title":"Experimental measurements of particle deposition in the human nasal airway.","authors":"Zhiwei Shen, Taye Tolu Mekonnen, Xinyu Cai, Liam Milton-McGurk, Hak-Kim Chan, Agisilaos Kourmatzis, Shaokoon Cheng","doi":"10.1016/j.ijpharm.2025.125280","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.125280","url":null,"abstract":"<p><p>Intranasal drug delivery is a promising non-invasive method for administering both local and systemic medications. While previous studies have extensively investigated the effects of particle size, airflow dynamics, and deposition locations on deposition efficiency, they have not focused on the thickness of deposited particles, which can significantly affect drug dissolution, absorption and therapeutic efficacy. This study investigates the deposition patterns of dry powder particles within the nasal airway, specifically examining how factors such as flow rates, particle size, and particle cohesiveness influence deposition patterns and their thickness. Using optical coherence tomography (OCT), this study assessed the deposition behaviour of three different lactose powders in a reconstructed nasal airway model at three key anatomical locations under varying flow rates (15, 35 and 55 L/min). Computational fluid dynamics (CFD) simulations were conducted to complement the experimental data, demonstrating the airflow dynamics in the nasal airway and highlighting recirculation zones that impact deposition patterns. The results revealed that the anterior section of the nasal airway is particularly effective at capturing particles, with localised flow patterns playing a critical role in particle accumulation. These flow patterns, combined with particle size and cohesiveness, are key factors in determining where and how particles cluster, leading to thicker deposition in specific areas of the nasal airway. This study addresses the gap in understanding how these factors influence deposition thickness and spatial distribution, ultimately contributing to the optimisation of nasal drug delivery systems.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"125280"},"PeriodicalIF":5.3,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Carbon quantum dots amplify beneficial effects of EGCG against neural injuries by NLRP3 inflammasome after intracerebral hemorrhage
IF 5.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-26 DOI: 10.1016/j.ijpharm.2025.125281
Min Xiao , Yun Pan , Shijin Tang , Tingwang Guo , Lin Yang , Gang Chen
Neuroinflammation plays an indispensable role in neural damages after ICH, responsible for the induced high mortality and poor prognosis. NLRP3 inflammasome, which is known mediated by ROS, has been widely documented to aggravate brain injuries. Therefore, suppressing neural injuries by ROS/NLRP3 pathway may be beneficial in treating ICH. As the major catechin found in green tea, epigallocatechin-3-gallate (EGCG) shows excellent anti-oxidative and anti-inflammatory effects. In this study, EGCG-carbon quantum dots (EGCG-CQDs) were successfully fabricated based on EGCG by hydrothermal synthesis method. EGCG-CQDs exhibited an excellent aqueous solubility, and emerged more abundant phenolic oxygens as well as oxygen-rich functional groups. Importantly, EGCG-CQDs showed superior free radical scavenging activity by DPPH and ABTS assays in vitro than EGCG. In vivo, a significant antioxidative activity was presented by EGCG-CQDs rather than EGCG. Furthermore, the upregulated NLRP3 and the induced inflammatory cascades (NF-κB, Caspase-1 and GSDMD) in ICH were attenuated by EGCG-CQDs. Inflammatory factor productions were also decreased by EGCG-CQDs, such as IL-1β, IL-18, IL-6 and TNF-α. Finally, the disturbed neural viability, disordered cytomorphology, and neurological deficits were significantly improved by EGCG-CQDs rather than EGCG. Therefore, CQDs might be an effective form to amplify the efficacy and bioavailability of EGCG, exerting considerable effects on treating ICH by suppressing ROS/NLRP3.
{"title":"Carbon quantum dots amplify beneficial effects of EGCG against neural injuries by NLRP3 inflammasome after intracerebral hemorrhage","authors":"Min Xiao ,&nbsp;Yun Pan ,&nbsp;Shijin Tang ,&nbsp;Tingwang Guo ,&nbsp;Lin Yang ,&nbsp;Gang Chen","doi":"10.1016/j.ijpharm.2025.125281","DOIUrl":"10.1016/j.ijpharm.2025.125281","url":null,"abstract":"<div><div>Neuroinflammation plays an indispensable role in neural damages after ICH, responsible for the induced high mortality and poor prognosis. NLRP3 inflammasome, which is known mediated by ROS, has been widely documented to aggravate brain injuries. Therefore, suppressing neural injuries by ROS/NLRP3 pathway may be beneficial in treating ICH. As the major catechin found in green tea, epigallocatechin-3-gallate (EGCG) shows excellent anti-oxidative and anti-inflammatory effects. In this study, EGCG-carbon quantum dots (EGCG-CQDs) were successfully fabricated based on EGCG by hydrothermal synthesis method. EGCG-CQDs exhibited an excellent aqueous solubility, and emerged more abundant phenolic oxygens as well as oxygen-rich functional groups. Importantly, EGCG-CQDs showed superior free radical scavenging activity by DPPH and ABTS assays in vitro than EGCG. In vivo, a significant antioxidative activity was presented by EGCG-CQDs rather than EGCG. Furthermore, the upregulated NLRP3 and the induced inflammatory cascades (NF-κB, Caspase-1 and GSDMD) in ICH were attenuated by EGCG-CQDs. Inflammatory factor productions were also decreased by EGCG-CQDs, such as IL-1β, IL-18, IL-6 and TNF-α. Finally, the disturbed neural viability, disordered cytomorphology, and neurological deficits were significantly improved by EGCG-CQDs rather than EGCG. Therefore, CQDs might be an effective form to amplify the efficacy and bioavailability of EGCG, exerting considerable effects on treating ICH by suppressing ROS/NLRP3.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"671 ","pages":"Article 125281"},"PeriodicalIF":5.3,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ultrasound-triggered release of vancomycin from a novel spinal device: Antibiotic release and efficacy in vivo
IF 5.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-26 DOI: 10.1016/j.ijpharm.2025.125276
Lauren J. Delaney , Priscilla Machado , Ji-Bin Liu , Rachel Evans , Asia Winslow , Neil Zhao , Christopher K. Kepler , Rajkishen Narayanan , Teeto Ezeonu , Viren Soni , Gagan Kaushal , Rachel Hilliard , Thomas P. Schaer , Noreen J. Hickok , Flemming Forsberg
Post-surgical spinal infection occurs in up to 20 % of patients, despite aggressive peri-operative antibiotic treatments. To improve prophylaxis, we have designed and evaluated an ultrasound-activated prophylactic antibiotic release system to combat post-surgical bacterial survival. Polylactic acid (PLA) clips (1 cm3) were 3D-printed with an interior reservoir (0.8 cm3) for carrying drug payload, specifically vancomycin (VAN). Under IACUC approval, clips were surgically implanted into the spines of sheep (n = 9) and swine (n = 2) by removing the spinous process at several levels of the lumbar spine. In the sheep, clips were insonated and the interstitial wound fluid was collected to quantify the ultrasound-triggered VAN release. Uninsonated control sheep exhibited an average VAN concentration of 6.32 ± 5.99 µg/mL after 72 h, while ultrasound-triggered clips released significantly higher VAN concentrations at 72 h (22.98 ± 11.22 µg/mL, p = 0.033). In the swine, device efficacy against Staphylococcus aureus was evaluated. Insonated sites saw significant reduction in colony forming units (CFU) to 4.3 ± 3.2 CFU in the activated clips, compared to uninsonated controls where bacterial colonization was higher (2898 ± 1214 CFU, p = 0.017). Overall, these results demonstrate the ability to non-invasively release VAN from an implanted reservoir in vivo, and that this VAN release is effective in mitigating invading microbes in the wound site
{"title":"Ultrasound-triggered release of vancomycin from a novel spinal device: Antibiotic release and efficacy in vivo","authors":"Lauren J. Delaney ,&nbsp;Priscilla Machado ,&nbsp;Ji-Bin Liu ,&nbsp;Rachel Evans ,&nbsp;Asia Winslow ,&nbsp;Neil Zhao ,&nbsp;Christopher K. Kepler ,&nbsp;Rajkishen Narayanan ,&nbsp;Teeto Ezeonu ,&nbsp;Viren Soni ,&nbsp;Gagan Kaushal ,&nbsp;Rachel Hilliard ,&nbsp;Thomas P. Schaer ,&nbsp;Noreen J. Hickok ,&nbsp;Flemming Forsberg","doi":"10.1016/j.ijpharm.2025.125276","DOIUrl":"10.1016/j.ijpharm.2025.125276","url":null,"abstract":"<div><div>Post-surgical spinal infection occurs in up to 20 % of patients, despite aggressive peri-operative antibiotic treatments. To improve prophylaxis, we have designed and evaluated an ultrasound-activated prophylactic antibiotic release system to combat post-surgical bacterial survival. Polylactic acid (PLA) clips (1 cm<sup>3</sup>) were 3D-printed with an interior reservoir (0.8 cm<sup>3</sup>) for carrying drug payload, specifically vancomycin (VAN). Under IACUC approval, clips were surgically implanted into the spines of sheep (n = 9) and swine (n = 2) by removing the spinous process at several levels of the lumbar spine. In the sheep, clips were insonated and the interstitial wound fluid was collected to quantify the ultrasound-triggered VAN release. Uninsonated control sheep exhibited an average VAN concentration of 6.32 ± 5.99 µg/mL after 72 h, while ultrasound-triggered clips released significantly higher VAN concentrations at 72 h (22.98 ± 11.22 µg/mL, p = 0.033). In the swine, device efficacy against <em>Staphylococcus aureus</em> was evaluated. Insonated sites saw significant reduction in colony forming units (CFU) to 4.3 ± 3.2 CFU in the activated clips, compared to uninsonated controls where bacterial colonization was higher (2898 ± 1214 CFU, p = 0.017). Overall, these results demonstrate the ability to non-invasively release VAN from an implanted reservoir <em>in vivo</em>, and that this VAN release is effective in mitigating invading microbes in the wound site</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"671 ","pages":"Article 125276"},"PeriodicalIF":5.3,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Abiraterone acetate fixed-dosed combinations with ibuprofen-based therapeutic eutectic and deep eutectic solvents
IF 5.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-26 DOI: 10.1016/j.ijpharm.2025.125279
Shaida Panbachi , Josef Beranek , Martin Kuentz
In recent years, deep eutectic solvents (DESs) with their outstanding solubilization properties have emerged as strong candidates for oral enabling formulations of poorly soluble drugs. This study explores the use of drug-based therapeutic DESs (THEDESs) to solubilize a poorly soluble compound with the aim of providing a fixed-dose combination of two complementary therapeutic agents. Specifically, potential anticancer effects of ibuprofen (IBU) are harnessed in a novel type of THEDES to dissolve higher amounts of abiraterone acetate (AbAc), an antitumor agent. Four IBU-based combinations were studied: 1:4 M ratio with octanoic acid (OctA), 1:5 with nonanoic acid (NonA), 1:3 with decanoic acid (DeA) or 1:2 with dodecanoic acid (DoA). Fatty acids of different chain lengths were analyzed and discussed considering surface charge densities obtained via quantum chemistry. The THEDESs listed could apparently dissolve AbAc amounts up to 1311.0 ± 125.4 mg/g in IBU:OctA THEDES, 1151.7 ± 22.2 mg/g in IBU:NonA, 1160.4 ± 33.5 mg/g in IBU:DeA, and 231.3 ± 10.7 mg/g in IBU:DoA. In vitro dissolution of the simultaneously released drugs reached 37.8 ± 9.0 % to 64.2 ± 1.0 % for IBU and 5.0 ± 3.3 % to 19.4 ± 0.1 % for AbAc. This increased to between 60.4 ± 2.8 % and 79.4 ± 5.0 % of released IBU, and 23.6 ± 1.0 % to 57.3 ± 5.8 % of released AbAc, with 20 % (w/w) Tween 80 added to the formulations. This showed the significant potential of drug-containing THEDESs as solubilizing agents for poorly soluble drugs, in the form of fixed-dose combinations of synergistic APIs.
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引用次数: 0
Formulation screening of lyophilized mRNA-lipid nanoparticles
IF 5.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-26 DOI: 10.1016/j.ijpharm.2025.125272
Anna Ruppl , Denis Kiesewetter , Monika Köll-Weber , Thomas Lemazurier , Regine Süss , Andrea Allmendinger
Lipid nanoparticles (LNPs) have demonstrated their therapeutic potential as safe and effective drug delivery systems for nucleic acids during the COVID-19 pandemic. However, one of the main challenges during technical CMC (Chemistry, Manufacturing, and Controls) development is their long-term stability at temperatures of 2–8 °C or higher, which may be improved by the removal of water by lyophilization. In this study, we identified lyo-/cryo-protectants for freeze-dried mRNA-LNP formulations beyond conventional excipients such as sucrose and trehalose as Tg-modifiers using polyA as a surrogate. Hydroxypropyl-beta-cyclodextrin, Kollidon® 12 PF (PVP), and dextran 40 kDa were tested in combinations to best stabilize the mRNA-LNPs during the lyophilization process as well as during storage for up to 6 months at 2–8 °C, 25 °C/60 % r.h., and 40 °C/75 % r.h.. We also tested the formulation principle including protectants in- and outside of the LNPs. Formulations were assessed for size, PDI, encapsulation efficiency, and properties related to the lyophilized dosage form. While 10 % (w/V) sucrose formulations successfully stabilized LNPs during the lyophilization process, they were not suitable for storage at temperatures beyond 2–8 °C. The most promising formulations for storage at higher temperatures were identified as 9 % (w/V) trehalose + 1 % (w/V) PVP with only a small increase in size over 6 months at 25 °C maintaining PDI and encapsulation efficiency. Results were verified with eGFP-mRNA-LNPs and tested in cell culture experiments. This study may serve as guidance for formulation scientists to further optimize freeze-dried mRNA-LNP formulations and eventually eliminate the cold chain for mRNA-LNP products.
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引用次数: 0
A comprehensive review of characterization techniques for particle adhesion and powder flowability 颗粒粘附性和粉末流动性表征技术综述。
IF 5.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-25 DOI: 10.1016/j.ijpharm.2024.125029
Leqi Lin , Yun Zhang , LiGe Wang , Xizhong Chen
The study of the flow properties of particles is crucial because it directly impacts the efficiency and product quality of various industrial particulate processes, such as continuous manufacturing of solid oral dosages. However, challenges arise due to the flow behavior of cohesive particles, which tend to adhere to surfaces or other particles, necessitating careful process design. The importance of selecting appropriate measurement pathways for accurate characterization has been overlooked. In response, an overview of measurement technologies for surface energy and cohesive/adhesive forces is provided in this work, aiming to establish a practical guide. Understanding these forces is crucial for optimizing continuous manufacturing processes to effectively mitigate flow-related issues such as obstructions, segregation, irregular flow, and flooding. Furthermore, various methods characterization experiments were conducted and compared to illuminate the methodological disparities. This analysis provides valuable insights into particle adhesion, cohesion, and powder flowability, potentially enhancing industrial particulate processes development.
颗粒流动特性的研究至关重要,因为它直接影响各种工业颗粒工艺的效率和产品质量,例如连续制造固体口服剂量。然而,由于粘性颗粒的流动行为,它们往往会粘附在表面或其他颗粒上,因此需要仔细设计工艺。选择合适的测量途径对准确表征的重要性被忽视了。因此,本文概述了表面能和内聚/粘附力的测量技术,旨在建立一个实用的指南。了解这些作用力对于优化连续制造过程至关重要,可以有效地缓解与流体相关的问题,如阻塞、分离、不规则流动和水浸。此外,还进行了各种方法表征实验,并进行了比较,以阐明方法上的差异。这种分析提供了有价值的见解颗粒粘附,凝聚力和粉末流动性,潜在地加强工业颗粒工艺的发展。
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引用次数: 0
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International Journal of Pharmaceutics
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