Pub Date : 2025-01-28DOI: 10.1016/j.ijpharm.2025.125256
Isaiah Gonzales , Rajarshi Sengupta , Sriramvignesh Mani , Clara E. Correa-Soto , Bhanu Bejgum , Fernando Alvarez-Nunez , Y.-H. Kiang
In a previous publication, we determined the kinetics and equilibrium for the sorption of propylparaben to polyvinyl chloride (PVC). In this work, we extend that study to investigate the sorption of methylparaben and propylparaben on tubing surfaces made of PVC and fluorinated ethylene propylene (FEP) using molecular dynamics simulations. The simulations suggest the mechanism of sorption to be adsorption. Experiments conducted to validate the simulations showed that both parabens undergo significant sorption to PVC, and no substantial sorption upon contact with FEP. The extent of sorption of propylparaben to PVC is much greater than that of methylparaben. Gibbs free energy of adsorption, calculated from the simulations provide insight into the extent of adsorption of the parabens to the polymer surfaces. Using this case study, we present a methodology to provide understanding of the compatibility between pharmaceutical ingredients and product contact materials when sorption is involved.
{"title":"Understanding the sorption of paraben on plastics using molecular dynamics simulations","authors":"Isaiah Gonzales , Rajarshi Sengupta , Sriramvignesh Mani , Clara E. Correa-Soto , Bhanu Bejgum , Fernando Alvarez-Nunez , Y.-H. Kiang","doi":"10.1016/j.ijpharm.2025.125256","DOIUrl":"10.1016/j.ijpharm.2025.125256","url":null,"abstract":"<div><div>In a previous publication, we determined the kinetics and equilibrium for the sorption of propylparaben to polyvinyl chloride (PVC). In this work, we extend that study to investigate the sorption of methylparaben and propylparaben on tubing surfaces made of PVC and fluorinated ethylene propylene (FEP) using molecular dynamics simulations. The simulations suggest the mechanism of sorption to be adsorption. Experiments conducted to validate the simulations showed that both parabens undergo significant sorption to PVC, and no substantial sorption upon contact with FEP. The extent of sorption of propylparaben to PVC is much greater than that of methylparaben. Gibbs free energy of adsorption, calculated from the simulations provide insight into the extent of adsorption of the parabens to the polymer surfaces. Using this case study, we present a methodology to provide understanding of the compatibility between pharmaceutical ingredients and product contact materials when sorption is involved.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"671 ","pages":"Article 125256"},"PeriodicalIF":5.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065530","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}
Bcl-2 protein plays an integral role in hijacking apoptosis and triggering chemoresistance in triple negative breast cancer (TNBC). The present study explored the therapeutic efficacy of Bcl-2 inhibitor i.e., venetoclax (VTX) loaded HP-β-CD NPs (VTX/HP-β-CD NPs) against TNBC. VTX/HP-β-CD NPs were prepared using nanoprecipitation method. The prepared nanoparticles had optimal size (∼217 ± 4.32 nm), narrow PDI (∼0.23 ± 0.01), higher drug loading (∼15.7 ± 1.94 %) and % entrapment efficiency (∼78.5 ± 1.09 %). Morphology assessment revealed a spherical shape. In-vitro release studies displayed sustained release for up to 72h. Moreover, VTX/HP-β-CD NPs exhibited higher cellular uptake, cytotoxicity, and apoptosis index than free drug. Furthermore, the IC50 values for VTX/HP-β-CD NPs were significantly reduced in 4T1 (∼3.96-fold) and MDA-MB-231 (∼5.23-fold) cells. Additionally, VTX/HP-β-CD NPs showed remarkable potential to induce “mixed cell death” by reducing the glutathione (GSH) levels and increasing ROS in TNBC cells. The pharmacokinetic studies showed a marked increase in the AUC0-∞ (∼2.12-fold), Cmax (∼1.05-fold), and t1/2 (∼1.66-fold). Also, anti-cancer efficacy studies in 4T1-based model revealed improved therapeutic efficacy of VTX when delivered via HP-β-CD NPs. Safety evaluation revealed no signs of toxicity. Overall, the prepared nanocarrier holds significant promise in enhancing the payload and efficacy of VTX.
{"title":"Crosslinked hydroxypropyl-β-cyclodextrin nanoparticles for improved efficacy of venetoclax against triple negative breast cancer","authors":"Simran Chandani , Sayali Dighe , Oly Katari , Vivek Yadav , Sanyog Jain","doi":"10.1016/j.ijpharm.2025.125296","DOIUrl":"10.1016/j.ijpharm.2025.125296","url":null,"abstract":"<div><div>Bcl-2 protein plays an integral role in hijacking apoptosis and triggering chemoresistance in triple negative breast cancer (TNBC). The present study explored the therapeutic efficacy of Bcl-2 inhibitor i.e., venetoclax (VTX) loaded HP-β-CD NPs (VTX/HP-β-CD NPs) against TNBC. VTX/HP-β-CD NPs were prepared using nanoprecipitation method. The prepared nanoparticles had optimal size (∼217 ± 4.32 nm), narrow PDI (∼0.23 ± 0.01), higher drug loading (∼15.7 ± 1.94 %) and % entrapment efficiency (∼78.5 ± 1.09 %). Morphology assessment revealed a spherical shape. <em>In-vitro</em> release studies displayed sustained release for up to 72h. Moreover, VTX/HP-β-CD NPs exhibited higher cellular uptake, cytotoxicity, and apoptosis index than free drug. Furthermore, the IC<sub>50</sub> values for VTX/HP-β-CD NPs were significantly reduced in 4T1 (∼3.96-fold) and MDA-MB-231 (∼5.23-fold) cells. Additionally, VTX/HP-β-CD NPs showed remarkable potential to induce “mixed cell death” by reducing the glutathione (GSH) levels and increasing ROS in TNBC cells. The pharmacokinetic studies showed a marked increase in the AUC<sub>0-∞</sub> (∼2.12-fold), C<sub>max</sub> (∼1.05-fold), and t<sub>1/2</sub> (∼1.66-fold). Also, anti-cancer efficacy studies in 4T1-based model revealed improved therapeutic efficacy of VTX when delivered via HP-β-CD NPs. Safety evaluation revealed no signs of toxicity. Overall, the prepared nanocarrier holds significant promise in enhancing the payload and efficacy of VTX.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"671 ","pages":"Article 125296"},"PeriodicalIF":5.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065512","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}
Supramolecular polymers represent a distinctive class of polymers exhibiting similarities with covalent polymers, while also showcasing distinctive attributes such as responsiveness, reversibility, self-healing, and dynamism, which are conferred upon them by non-covalent interactions including hydrogen bonding, electrostatic interactions, van der Waals forces, π-π arrangements, and donor–acceptor interactions, among others. The noteworthy features of these supramolecular polymers have attracted considerable interest across diverse fields of science and technology, spanning electrochemistry, environmental science, drug delivery and tissue engineering. Nonetheless, the prevailing research focus in the realm of supramolecular polymers revolves around the advancement of novel methodologies aimed at synthesizing a broad spectrum of polymers characterized by diverse topologies. However, to fully capitalize on their potential applications within these domains, it is imperative to scrutinize these versatile polymers through the lens of thermodynamic and kinetic stability. Moreover, their integration into healthcare and medical realms necessitates rigorous assessment of safety and biocompatibility attributes. Thus, the present review endeavours to critically evaluate supramolecular polymers from perspectives of stability, safety, and regulatory considerations, thereby elucidating their potential for translation into commercial domains.
{"title":"Supramolecular polymers: A perspective on the stability, biocompatibility and regulatory aspects","authors":"Samia Shaikh, Padakanti Sandeep Chary, Neelesh Kumar Mehra","doi":"10.1016/j.ijpharm.2025.125277","DOIUrl":"10.1016/j.ijpharm.2025.125277","url":null,"abstract":"<div><div>Supramolecular polymers represent a distinctive class of polymers exhibiting similarities with covalent polymers, while also showcasing distinctive attributes such as responsiveness, reversibility, self-healing, and dynamism, which are conferred upon them by non-covalent interactions including hydrogen bonding, electrostatic interactions, van der Waals forces, π-π arrangements, and donor–acceptor interactions, among others. The noteworthy features of these supramolecular polymers have attracted considerable interest across diverse fields of science and technology, spanning electrochemistry, environmental science, drug delivery and tissue engineering. Nonetheless, the prevailing research focus in the realm of supramolecular polymers revolves around the advancement of novel methodologies aimed at synthesizing a broad spectrum of polymers characterized by diverse topologies. However, to fully capitalize on their potential applications within these domains, it is imperative to scrutinize these versatile polymers through the lens of thermodynamic and kinetic stability. Moreover, their integration into healthcare and medical realms necessitates rigorous assessment of safety and biocompatibility attributes. Thus, the present review endeavours to critically evaluate supramolecular polymers from perspectives of stability, safety, and regulatory considerations, thereby elucidating their potential for translation into commercial domains.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"671 ","pages":"Article 125277"},"PeriodicalIF":5.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065315","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}
Androgenic alopecia (AGA), the most prevalent type of progressive hair loss, currently lacks an effective topical treatment regimen. In this study, we synthesized an ionic liquid (IL) to co-solubilize minoxidil (MXD) and finasteride (FIN) and subsequently formulated them into an in situ thermosensitive ionic liquid/cyclodextrin/poloxamer hydrogel (ICPG), termed M + F@ICPG. M + F@ICPG was developed for the transdermal co-delivery of these two drugs, aiming to provide a multipath therapeutic approach for AGA while avoiding the adverse effects commonly associated with oral FIN and topical MXD tincture. The thermosensitive characteristics, skin penetration, hair follicle (HF) targeting efficiency, biosafety, and in vivo therapeutic efficacy of M + F@ICPG were evaluated using an AGA mouse model. Our results demonstrated that M + F@ICPG was a thermosensitive hydrogel, transitioning from solution to gel upon contact with the scalp. Compared to the FIN suspension and MXD tincture, M + F@ICPG significantly enhanced the skin penetration (∼2.2-fold) and retention (∼8.6-fold) of FIN and increased the relative retention of MXD (∼6.3-fold) in the skin. Moreover, M + F@ICPG exhibited a HF targeting index of 1.74 for MXD and 1.46 for FIN, indicating enhanced drug targeting to HF. M + F@ICPG showed superior in vivo efficacy in terms of hair regeneration, anagen recovery, inflammation mitigation, and microvessel reconstruction. The underlying mechanism was attributed to the upregulation of hair growth genes, downregulation of hair loss genes, and reduction of abnormally elevated inflammatory factors. These findings suggest that this novel M + F@ICPG is a promising topical co-delivery system for the synergistic treatment of AGA.
{"title":"Co-delivery of minoxidil and finasteride via ionic liquid and cyclodextrin-assisted in situ thermosensitive hydrogel for synergistic treatment of androgenic alopecia","authors":"Ziyi Liu, Xiaojuan Li, Sha Xiong, Ting Xiao, Siwen Jiao, Guihong Chai, Yuehong Xu","doi":"10.1016/j.ijpharm.2025.125263","DOIUrl":"10.1016/j.ijpharm.2025.125263","url":null,"abstract":"<div><div>Androgenic alopecia (AGA), the most prevalent type of progressive hair loss, currently lacks an effective topical treatment regimen. In this study, we synthesized an ionic liquid (IL) to co-solubilize minoxidil (MXD) and finasteride (FIN) and subsequently formulated them into an in situ thermosensitive ionic liquid/cyclodextrin/poloxamer hydrogel (ICPG), termed M + F@ICPG. M + F@ICPG was developed for the transdermal co-delivery of these two drugs, aiming to provide a multipath therapeutic approach for AGA while avoiding the adverse effects commonly associated with oral FIN and topical MXD tincture. The thermosensitive characteristics, skin penetration, hair follicle (HF) targeting efficiency, biosafety, and <em>in vivo</em> therapeutic efficacy of M + F@ICPG were evaluated using an AGA mouse model. Our results demonstrated that M + F@ICPG was a thermosensitive hydrogel, transitioning from solution to gel upon contact with the scalp. Compared to the FIN suspension and MXD tincture, M + F@ICPG significantly enhanced the skin penetration (∼2.2-fold) and retention (∼8.6-fold) of FIN and increased the relative retention of MXD (∼6.3-fold) in the skin. Moreover, M + F@ICPG exhibited a HF targeting index of 1.74 for MXD and 1.46 for FIN, indicating enhanced drug targeting to HF. M + F@ICPG showed superior <em>in vivo</em> efficacy in terms of hair regeneration, anagen recovery, inflammation mitigation, and microvessel reconstruction. The underlying mechanism was attributed to the upregulation of hair growth genes, downregulation of hair loss genes, and reduction of abnormally elevated inflammatory factors. These findings suggest that this novel M + F@ICPG is a promising topical co-delivery system for the synergistic treatment of AGA.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"671 ","pages":"Article 125263"},"PeriodicalIF":5.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046693","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}
Pub Date : 2025-01-27DOI: 10.1016/j.ijpharm.2025.125243
Tom Verbeek , Alexander De Man , Melissa Debacker , Bram Bekaert , Bernd Van Snick , Martin Otava , Chris Vervaet , Valérie Vanhoorne
In recent years, CM has become increasingly popular in the pharmaceutical industry for the production of OSD forms. Most of the newly developed APIs nowadays are extremely cohesive and sticky with a mean particle size particle of 100 , a wide PSD and a high tendency to agglomerate, making them difficult to accurately dose using loss-in-weight equipment during CM. In this research paper, the effect of various glidants on the volumetric and gravimetric feeding of several APIs was assessed. Three challenging API (APAP, MPT and SD) and four different glidants (Aerosil® 200, Aerosil® R972, Syloid® 244FP and TRI-CAFOS® 200-7) were selected. For all feeding trials, a GEA CF equipped with 20 mm concave screws was used, in combination with an external catch scale. The volumetric feeding trials showed the ability of each glidant to increase the max and reduce the movRSD40 and the decay for the cohesive APIs (APAP and MPT). Although the fumed silica grades showed the highest impact on the previously mentioned feeding parameters, low AE10 values were obtained, negatively affecting the feeding performance at higher glidant concentration. Both Syloid 244FP and TCP were good alternatives. However, to obtain a similar feeding performance a higher concentration of these glidants is required. The volumetric trials showed that glidant addition has no additional benefits for APIs with good flow properties such as SD. The second part of this paper discussed the impact of glidant addition on the gravimetric feeding behavior of the cohesive powders. Both the fumed silica grades (Aerosil® 200 and Aerosil® R972) and Syloid 244FP lowered the deviation on all LC% profiles of the cohesive APIs. In contrast to the volumetric trails, blends with excess fumed silica resulted in low AE10 values which are efficiently dosed by the CF during the gravimetric feeding.
{"title":"The impact of glidant addition on the loss-in-weight feeding of active pharmaceutical ingredients","authors":"Tom Verbeek , Alexander De Man , Melissa Debacker , Bram Bekaert , Bernd Van Snick , Martin Otava , Chris Vervaet , Valérie Vanhoorne","doi":"10.1016/j.ijpharm.2025.125243","DOIUrl":"10.1016/j.ijpharm.2025.125243","url":null,"abstract":"<div><div>In recent years, CM has become increasingly popular in the pharmaceutical industry for the production of OSD forms. Most of the newly developed APIs nowadays are extremely cohesive and sticky with a mean particle size particle of <span><math><mo><</mo></math></span>100 <span><math><mrow><mi>μ</mi><mi>m</mi></mrow></math></span>, a wide PSD and a high tendency to agglomerate, making them difficult to accurately dose using loss-in-weight equipment during CM. In this research paper, the effect of various glidants on the volumetric and gravimetric feeding of several APIs was assessed. Three challenging API (APAP<span><math><mi>μ</mi></math></span>, MPT and SD) and four different glidants (Aerosil® 200, Aerosil® R972, Syloid® 244FP and TRI-CAFOS® 200-7) were selected. For all feeding trials, a GEA CF equipped with 20 mm concave screws was used, in combination with an external catch scale. The volumetric feeding trials showed the ability of each glidant to increase the <span><math><mrow><mi>F</mi><mi>F</mi></mrow></math></span> <sub>max</sub> and reduce the <span><math><mrow><mi>F</mi><mi>F</mi></mrow></math></span> <sub>movRSD40</sub> and the <span><math><mrow><mi>F</mi><mi>F</mi></mrow></math></span> <sub>decay</sub> for the cohesive APIs (APAP<span><math><mi>μ</mi></math></span> and MPT). Although the fumed silica grades showed the highest impact on the previously mentioned feeding parameters, low AE10 values were obtained, negatively affecting the feeding performance at higher glidant concentration. Both Syloid 244FP and TCP were good alternatives. However, to obtain a similar feeding performance a higher concentration of these glidants is required. The volumetric trials showed that glidant addition has no additional benefits for APIs with good flow properties such as SD. The second part of this paper discussed the impact of glidant addition on the gravimetric feeding behavior of the cohesive powders. Both the fumed silica grades (Aerosil® 200 and Aerosil® R972) and Syloid 244FP lowered the deviation on all LC% profiles of the cohesive APIs. In contrast to the volumetric trails, blends with excess fumed silica resulted in low AE10 values which are efficiently dosed by the CF during the gravimetric feeding.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"671 ","pages":"Article 125243"},"PeriodicalIF":5.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065529","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}
Pub Date : 2025-01-27DOI: 10.1016/j.ijpharm.2025.125288
Alice J. Turner , Elke Prasad , Alastair J. Florence , Gavin W. Halbert
Oral drug delivery remains the preferred method of drug administration but due to poor solubility many active pharmaceutical ingredients (APIs) are ill suited to this. A number of methods to improve solubility of poorly soluble Biopharmaceutical Classification System (BCS) Class II drugs already exist but there is a lack of scalable, flexible methods. As such the current study applies the innovative technique of aerosol jet printing to increase the dissolution capabilities of a Class II drug in a manner which permits flexibility to allow dosage form tailoring. Aerosol jet printing provided a high degree of control allowing effective scaling, by size and layering, and control over drug distribution. Aerosol jet printing of pure active pharmaceutical ingredient (fenofibrate) resulted in crystalline material but as polymer excipient content was increased, morphological changes occurred and a fully amorphous product was generated on inclusion of 75 % (w/w solute) polymer content or above. This amorphous product has been found to exhibit a 10-fold increase in drug dissolution relative to comparable physical mixtures. In conclusion, aerosol jet printing is a novel and effective, scalable method providing improved dissolution coupled with high spatial precision and warrants further investigation.
{"title":"Investigation of aerosol jet printing for the preparation of solid dosage forms","authors":"Alice J. Turner , Elke Prasad , Alastair J. Florence , Gavin W. Halbert","doi":"10.1016/j.ijpharm.2025.125288","DOIUrl":"10.1016/j.ijpharm.2025.125288","url":null,"abstract":"<div><div>Oral drug delivery remains the preferred method of drug administration but due to poor solubility many active pharmaceutical ingredients (APIs) are ill suited to this. A number of methods to improve solubility of poorly soluble Biopharmaceutical Classification System (BCS) Class II drugs already exist but there is a lack of scalable, flexible methods. As such the current study applies the innovative technique of aerosol jet printing to increase the dissolution capabilities of a Class II drug in a manner which permits flexibility to allow dosage form tailoring. Aerosol jet printing provided a high degree of control allowing effective scaling, by size and layering, and control over drug distribution. Aerosol jet printing of pure active pharmaceutical ingredient (fenofibrate) resulted in crystalline material but as polymer excipient content was increased, morphological changes occurred and a fully amorphous product was generated on inclusion of 75 % (w/w solute) polymer content or above. This amorphous product has been found to exhibit a 10-fold increase in drug dissolution relative to comparable physical mixtures. In conclusion, aerosol jet printing is a novel and effective, scalable method providing improved dissolution coupled with high spatial precision and warrants further investigation.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"671 ","pages":"Article 125288"},"PeriodicalIF":5.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065515","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}
Pub Date : 2025-01-27DOI: 10.1016/j.ijpharm.2025.125285
Yuhan Ding , Caiting Deng , Yuchen Yang , Jingjing Zhang , Wen Liu , Omer Aras , Feifei An , Jun Liu , Yichao Chai
Both photothermal therapy (PTT) and chemodynamic therapy (CDT) are designed to focus their antitumor effect on only the tumor site, thereby minimizing unwanted severe damage to healthy tissue outside the tumor. However, each monotherapy is limited in achieving complete tumor eradication, resulting in tumor recurrence. The combination of multiple therapies may help to overcome the limitations of single therapy, improve the chances of complete tumor eradication, and reduce the risk of recurrence. Here, we report a novel multifunctional carrier-free nanoparticle, namely Mn-TPP@ICG, prepared through the self-assembly of ICG and 5,10,15,20-Tetraphenyl-21H,23H-porphine manganese (III) chloride (Mn-TPP). The prepared Mn-TPP@ICG allowed dual-mode imaging in the form of magnetic resonance imaging (MRI) and near-infrared (NIR) fluorescence imaging, as well as combination therapy in the form of CDT and PTT. In vitro experiments revealed that Mn-TPP@ICG nanoparticles can enable CDT by converting intratumoral hydrogen peroxide (H2O2) to highly cytotoxic hydroxyl radicals (·OH) and PTT through photothermal conversion, resulting in a strong synergistic antitumor effect. Furthermore, in vivo experiments revealed that CDT and PTT with Mn-TPP@ICG nanoparticles effected a synergistically enhanced therapeutic effect in 4T1 tumor-bearing mice, significantly inhibiting tumor growth compared with monomodal treatments with no treatment, only CDT, or only PTT. Lastly, imaging experiments unveiled the exceptional capability of Mn-TPP@ICG nanoparticles in enabling fluorescence imaging and high-resolution MRI upon their intravenous administration. Thus, a meaningful carrier-free nanoparticle strategy for the synergistic combination of CDT and PTT was provided in our study, broadening the applications of nanotheranostics.
{"title":"Carrier-free nanoparticles for cancer theranostics with dual-mode magnetic resonance imaging/fluorescence imaging and combination photothermal and chemodynamic therapy","authors":"Yuhan Ding , Caiting Deng , Yuchen Yang , Jingjing Zhang , Wen Liu , Omer Aras , Feifei An , Jun Liu , Yichao Chai","doi":"10.1016/j.ijpharm.2025.125285","DOIUrl":"10.1016/j.ijpharm.2025.125285","url":null,"abstract":"<div><div>Both photothermal therapy (PTT) and chemodynamic therapy (CDT) are designed to focus their antitumor effect on only the tumor site, thereby minimizing unwanted severe damage to healthy tissue outside the tumor. However, each monotherapy is limited in achieving complete tumor eradication, resulting in tumor recurrence. The combination of multiple therapies may help to overcome the limitations of single therapy, improve the chances of complete tumor eradication, and reduce the risk of recurrence. Here, we report a novel multifunctional carrier-free nanoparticle, namely Mn-TPP@ICG, prepared through the self-assembly of ICG and 5,10,15,20-Tetraphenyl-21H,23H-porphine manganese (III) chloride (Mn-TPP). The prepared Mn-TPP@ICG allowed dual-mode imaging in the form of magnetic resonance imaging (MRI) and near-infrared (NIR) fluorescence imaging, as well as combination therapy in the form of CDT and PTT. <em>In vitro</em> experiments revealed that Mn-TPP@ICG nanoparticles can enable CDT by converting intratumoral hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) to highly cytotoxic hydroxyl radicals (·OH) and PTT through photothermal conversion, resulting in a strong synergistic antitumor effect. Furthermore, <em>in vivo</em> experiments revealed that CDT and PTT with Mn-TPP@ICG nanoparticles effected a synergistically enhanced therapeutic effect in 4T1 tumor-bearing mice, significantly inhibiting tumor growth compared with monomodal treatments with no treatment, only CDT, or only PTT. Lastly, imaging experiments unveiled the exceptional capability of Mn-TPP@ICG nanoparticles in enabling fluorescence imaging and high-resolution MRI upon their intravenous administration. Thus, a meaningful carrier-free nanoparticle strategy for the synergistic combination of CDT and PTT was provided in our study, broadening the applications of nanotheranostics.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"671 ","pages":"Article 125285"},"PeriodicalIF":5.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065511","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}
Pub Date : 2025-01-27DOI: 10.1016/j.ijpharm.2025.125290
Rui Wang , Han Wang , Rui Yao , Yan Li , Sedrati Manar , Lei Nie , Khaydar E. Yunusov , Jianwei Pan , Guohua Jiang
An iontophoresis-driven porous microneedles (IPMNs) system has been developed for hyperuricemia management, which can be effectively prolong the anti-hyperuricemia effect. Porous microneedles (PMNs) with good biocompatibility, high porous volume, and excellent substance exchange capacity were firstly prepared for drug transdermal delivery and active iontophoresis. In vitro experiments showed that the transdermal delivery efficiency of anti-hyperuricemia drug (Allopurinol, AP) could be controlled using the iontophoresis current of IPMNs system. The AP release amount could be increased to 1.54 mg with iontophoresis under constant voltage of 1.5 V for 30 min. In vivo transdermal delivery of AP on mice models using IPMNs system exhibited an effective anti-hyperuricemia response. The serum uric acid (SUA) level could be dropped to ∼ 158.2 μmol/L within 2 h, and maintaining for 7 h under the normal level, leading a long-term therapeutic effect. This IPMNs system exhibits a low cost, user-friendly, and active delivery, showing great potential for hyperuricemia self-administration.
{"title":"Iontophoresis-driven transdermal drug delivery system based on porous microneedles for hyperuricemia treatment","authors":"Rui Wang , Han Wang , Rui Yao , Yan Li , Sedrati Manar , Lei Nie , Khaydar E. Yunusov , Jianwei Pan , Guohua Jiang","doi":"10.1016/j.ijpharm.2025.125290","DOIUrl":"10.1016/j.ijpharm.2025.125290","url":null,"abstract":"<div><div>An iontophoresis-driven porous microneedles (IPMNs) system has been developed for hyperuricemia management, which can be effectively prolong the anti-hyperuricemia effect. Porous microneedles (PMNs) with good biocompatibility, high porous volume, and excellent substance exchange capacity were firstly prepared for drug transdermal delivery and active iontophoresis.<em> <!-->In vitro</em> experiments showed that the transdermal delivery efficiency of anti-hyperuricemia drug (Allopurinol, AP) could be controlled using the iontophoresis current of IPMNs system. The AP release amount could be increased to 1.54 mg with iontophoresis under constant voltage of 1.5 V for 30 min. <em>In vivo</em> transdermal delivery of AP on mice models using IPMNs system exhibited an effective anti-hyperuricemia response. The serum uric acid (SUA) level could be dropped to ∼ 158.2 μmol/L within 2 h, and maintaining for 7 h under the normal level, leading a long-term therapeutic effect. This IPMNs system exhibits a low cost, user-friendly, and active delivery, showing great potential for hyperuricemia self-administration.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"671 ","pages":"Article 125290"},"PeriodicalIF":5.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064388","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}
Pub Date : 2025-01-27DOI: 10.1016/j.ijpharm.2025.125291
Yuting Zhang , Hanqi Wang , Caili Xu , Xiaomiao Ye , Yanyang Nan , Xiaozhi Hu , Jiajun Fan , Xuebin Wang , Dianwen Ju
Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic liver disorder worldwide, and effective therapeutic strategies for its treatment remains limited. In this article, we introduced Glipo-siRubi, a hepatocytes-targeting RNA interference (RNAi) nanoliposome for suppression of Rubicon expression, aiming to achieve precise regulation of autophagy in NAFLD. Autophagy activation induced by Rubicon suppression resulted in reduced endoplasmic reticulum stress and intracellular lipid accumulation in vitro. Moreover, Glipo-siRubi administration exhibited remarkable therapeutic efficacy, characterized by decreased liver lipid accumulation, ameliorated histopathology and improved insulin sensitivity in mice with western diet, indicating its notable potential against NAFLD. By inducing autophagy activation, the hepatocytes-targeting Glipo-siRubi provided a promising method for NAFLD treatment, addressing the limitations of current approaches. Our study highlighted the significance of Rubicon-specific suppression in NAFLD treatment, offering a specific, safe, and efficient approach to mitigate NAFLD.
{"title":"Rubicon siRNA-encapsulated liver-targeting nanoliposome is a promising therapeutic for non-alcoholic fatty liver disease","authors":"Yuting Zhang , Hanqi Wang , Caili Xu , Xiaomiao Ye , Yanyang Nan , Xiaozhi Hu , Jiajun Fan , Xuebin Wang , Dianwen Ju","doi":"10.1016/j.ijpharm.2025.125291","DOIUrl":"10.1016/j.ijpharm.2025.125291","url":null,"abstract":"<div><div>Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic liver disorder worldwide, and effective therapeutic strategies for its treatment remains limited. In this article, we introduced Glipo-siRubi, a hepatocytes-targeting RNA interference (RNAi) nanoliposome for suppression of Rubicon expression, aiming to achieve precise regulation of autophagy in NAFLD. Autophagy activation induced by Rubicon suppression resulted in reduced endoplasmic reticulum stress and intracellular lipid accumulation <em>in vitro</em>. Moreover, Glipo-siRubi administration exhibited remarkable therapeutic efficacy, characterized by decreased liver lipid accumulation, ameliorated histopathology and improved insulin sensitivity in mice with western diet, indicating its notable potential against NAFLD. By inducing autophagy activation, the hepatocytes-targeting Glipo-siRubi provided a promising method for NAFLD treatment, addressing the limitations of current approaches. Our study highlighted the significance of Rubicon-specific suppression in NAFLD treatment, offering a specific, safe, and efficient approach to mitigate NAFLD.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"672 ","pages":"Article 125291"},"PeriodicalIF":5.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065212","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}
Pub Date : 2025-01-27DOI: 10.1016/j.ijpharm.2025.125282
Li Li , Mei Luo , Lifang Zhou , Yanhong Wang , Yaoge Jiao , Chunting Wang , Changyang Gong , Xiaobo Cen , Shaohua Yao
Lipid nanoparticles (LNPs) are among the most promising non-viral mRNA delivery systems for gene therapeutic applications. However, the in vivo delivery of LNP-mRNA remains challenging due to multiple intrinsic barriers that hinder LNPs from reaching their target cells. In this study, we sought to enhance LNP delivery by manipulating intrinsic regulatory mechanisms involved in their metabolism. We demonstrated that activation of the glucocorticoid pathway significantly increased the systemic delivery of LNP-mRNA in both mice and monkeys, achieving up to a fourfold improvement. This enhancement was primarily attributed to the glucocorticoid-mediated inhibition of macrophage phagocytosis in circulation and the liver, which resulted in higher LNP accumulation in hepatocytes. Consequently, glucocorticoid activation improved the therapeutic efficacy of LNP-based protein replacement and CRISPR/Cas9 genome editing therapies. Together, these findings establish a practical strategy to enhance the systemic delivery of RNA-based protein replacement and genome editing therapeutics, highlighting the potential of manipulating endogenous mechanisms to optimize exogenous gene delivery.
{"title":"Glucocorticoid pre-administration improves LNP-mRNA mediated protein replacement and genome editing therapies","authors":"Li Li , Mei Luo , Lifang Zhou , Yanhong Wang , Yaoge Jiao , Chunting Wang , Changyang Gong , Xiaobo Cen , Shaohua Yao","doi":"10.1016/j.ijpharm.2025.125282","DOIUrl":"10.1016/j.ijpharm.2025.125282","url":null,"abstract":"<div><div>Lipid nanoparticles (LNPs) are among the most promising non-viral mRNA delivery systems for gene therapeutic applications. However, the in vivo delivery of LNP-mRNA remains challenging due to multiple intrinsic barriers that hinder LNPs from reaching their target cells. In this study, we sought to enhance LNP delivery by manipulating intrinsic regulatory mechanisms involved in their metabolism. We demonstrated that activation of the glucocorticoid pathway significantly increased the systemic delivery of LNP-mRNA in both mice and monkeys, achieving up to a fourfold improvement. This enhancement was primarily attributed to the glucocorticoid-mediated inhibition of macrophage phagocytosis in circulation and the liver, which resulted in higher LNP accumulation in hepatocytes. Consequently, glucocorticoid activation improved the therapeutic efficacy of LNP-based protein replacement and CRISPR/Cas9 genome editing therapies. Together, these findings establish a practical strategy to enhance the systemic delivery of RNA-based protein replacement and genome editing therapeutics, highlighting the potential of manipulating endogenous mechanisms to optimize exogenous gene delivery.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"672 ","pages":"Article 125282"},"PeriodicalIF":5.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065514","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}
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