Pub Date : 2025-02-10DOI: 10.1016/j.ijpx.2025.100317
Jianling Hu , Yue An , Weiqing Wang , Jing Yang , Wenxin Niu , Xiumei Jiang , Kun Li , Changzhao Jiang , Jincui Ye
The conventional oral administration of pioglitazone for Type II diabetes management is frequently compromised by hepatic first-pass metabolism and associated systemic adverse effects, necessitating the development of enhanced transdermal delivery approaches. This study developed a transdermal drug delivery system combining conductive hydrogel microneedles and iontophoresis to improve the transdermal delivery of pioglitazone hydrochloride (PIO) and its therapeutic efficacy in the treatment of type II diabetes. The microneedles, fabricated using poly(methyl vinyl ether-alt-maleic anhydride) as the main matrix material, exhibited excellent conductivity, mechanical strength, and high drug loading capacity. In vitro permeation experiments demonstrated that, when combined with iontophoresis at a current intensity of 0.5 mA, the cumulative permeation of PIO reached 238.1 ± 27.14 μg/cm2 within 48 h, significantly higher than that of the microneedle group alone. In a type II diabetic rat model, the microneedle-iontophoresis system displayed a significantly better hypoglycemic effect than the oral administration group, with a blood glucose reduction of 6.3 mmol/L on day 8, significantly higher than the 5.1 mmol/L reduction in the positive control group. Pharmacokinetic analysis indicated that the Tmax, T1/2, and mean residence time of the system were longer than those of oral administration, indicating sustained-release characteristics. Skin irritation tests revealed that the system caused only mild, transient skin irritation, with complete skin recovery within 24 h. In conclusion, conductive hydrogel microneedles combined with iontophoresis can effectively enhance PIO transdermal delivery, bioavailability, and therapeutic efficacy while also exhibiting good safety and potential clinical application value.
{"title":"Enhanced transdermal delivery of pioglitazone hydrochloride via conductive hydrogel microneedles combined with iontophoresis","authors":"Jianling Hu , Yue An , Weiqing Wang , Jing Yang , Wenxin Niu , Xiumei Jiang , Kun Li , Changzhao Jiang , Jincui Ye","doi":"10.1016/j.ijpx.2025.100317","DOIUrl":"10.1016/j.ijpx.2025.100317","url":null,"abstract":"<div><div>The conventional oral administration of pioglitazone for Type II diabetes management is frequently compromised by hepatic first-pass metabolism and associated systemic adverse effects, necessitating the development of enhanced transdermal delivery approaches. This study developed a transdermal drug delivery system combining conductive hydrogel microneedles and iontophoresis to improve the transdermal delivery of pioglitazone hydrochloride (PIO) and its therapeutic efficacy in the treatment of type II diabetes. The microneedles, fabricated using poly(methyl vinyl ether-<em>alt</em>-maleic anhydride) as the main matrix material, exhibited excellent conductivity, mechanical strength, and high drug loading capacity. In vitro permeation experiments demonstrated that, when combined with iontophoresis at a current intensity of 0.5 mA, the cumulative permeation of PIO reached 238.1 ± 27.14 μg/cm<sup>2</sup> within 48 h, significantly higher than that of the microneedle group alone. In a type II diabetic rat model, the microneedle-iontophoresis system displayed a significantly better hypoglycemic effect than the oral administration group, with a blood glucose reduction of 6.3 mmol/L on day 8, significantly higher than the 5.1 mmol/L reduction in the positive control group. Pharmacokinetic analysis indicated that the T<sub>max</sub>, T<sub>1/2</sub>, and mean residence time of the system were longer than those of oral administration, indicating sustained-release characteristics. Skin irritation tests revealed that the system caused only mild, transient skin irritation, with complete skin recovery within 24 h. In conclusion, conductive hydrogel microneedles combined with iontophoresis can effectively enhance PIO transdermal delivery, bioavailability, and therapeutic efficacy while also exhibiting good safety and potential clinical application value.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100317"},"PeriodicalIF":5.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396007","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}
Percutaneous neoadjuvant therapy has proven effective in diminishing tumor size and the surgical intervention area, which couldeffectively mitigate the risk of tumor recurrence and enhance immunotherapy efficacy. Lenalidomide, an approved medication orally used to treat myeloma, was loaded into nanosuspensions-based hydrogels (Len-NBHs) for transdermal administration as a percutaneous neoadjuvant therapy. This study was designed to investigate the inhibitory effect and mechanism of Len-NBHs on melanoma. Network pharmacology and transcriptomic analyses identified key targets and signaling pathways. The effects of lenalidomide on melanoma were further verified through Western blotting, immunohistochemistry, immunofluorescence, and quantitative real-time polymerase chain reaction，using both in vitro cell experiments and in vivo melanoma mouse models. Lenalidomide could induce melanoma cells apoptosis, disrupt cell cycle progression, impede cell migration and invasion, and modify tumor microenvironment (TME). Mechanistically, lenalidomide reversed the abnormal activation of the PI3K-AKT signaling pathway and the overexpression of CD93, while also recruiting CD8+ T cells, CD4+ T cells, and dendritic cells to infiltrate the tumor site. Transdermal administration of Len-NBHs represents a promising adjuvant therapy for the treatment of malignant melanoma. Preoperative administration of Len-NBHs can inhibit the outward spread of melanoma, reduce tumor size, thereby decreasing the surgical excision area and improving patient survival rates and prognosis.
{"title":"Topical transdermal administration of lenalidomide nanosuspensions-based hydrogels against melanoma: In vitro and in vivo studies","authors":"Mengdi Zhang , Haiying Qiu , Zheyi Han, Yazhong Ma, Jingjing Hou, Jingwei Yuan, Haiyan Jia, Menglu Zhou, Hongjie Lu, Yan Wu","doi":"10.1016/j.ijpx.2025.100316","DOIUrl":"10.1016/j.ijpx.2025.100316","url":null,"abstract":"<div><div>Percutaneous neoadjuvant therapy has proven effective in diminishing tumor size and the surgical intervention area, which couldeffectively mitigate the risk of tumor recurrence and enhance immunotherapy efficacy. Lenalidomide, an approved medication orally used to treat myeloma, was loaded into nanosuspensions-based hydrogels (Len-NBHs) for transdermal administration as a percutaneous neoadjuvant therapy. This study was designed to investigate the inhibitory effect and mechanism of Len-NBHs on melanoma. Network pharmacology and transcriptomic analyses identified key targets and signaling pathways. The effects of lenalidomide on melanoma were further verified through Western blotting, immunohistochemistry, immunofluorescence, and quantitative real-time polymerase chain reaction，using both in vitro cell experiments and in vivo melanoma mouse models. Lenalidomide could induce melanoma cells apoptosis, disrupt cell cycle progression, impede cell migration and invasion, and modify tumor microenvironment (TME). Mechanistically, lenalidomide reversed the abnormal activation of the PI3K-AKT signaling pathway and the overexpression of CD93, while also recruiting CD8+ T cells, CD4+ T cells, and dendritic cells to infiltrate the tumor site. Transdermal administration of Len-NBHs represents a promising adjuvant therapy for the treatment of malignant melanoma. Preoperative administration of Len-NBHs can inhibit the outward spread of melanoma, reduce tumor size, thereby decreasing the surgical excision area and improving patient survival rates and prognosis.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100316"},"PeriodicalIF":5.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079842","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 : 2024-12-25DOI: 10.1016/j.ijpx.2024.100314
Zhenghao Ai , Bingyao Liu , Junyan Chen , Xinhao Zeng , Ke Wang , Chao Tao , Jing Chen , Liuxuan Yang , Qian Ding , Meiling Zhou
Cancer remains one of the leading causes of death worldwide, highlighting the urgent need for novel antitumor drugs. Natural products have long been a crucial source of anticancer agents. Among these, emodin (EMO), a multifunctional anthraquinone compound, exhibits significant anticancer effects but is hindered in clinical applications by challenges such as low solubility, rapid metabolism, poor bioavailability, and off-target toxicity. Nano drug delivery systems offer effective strategies to overcome these limitations by enhancing the solubility, stability, bioavailability, and targeting ability of EMO. While substantial progress has been made in developing EMO-loaded nanoformulations, a comprehensive review on this topic is still lacking. This paper aims to fill this gap by providing an overview of recent advancements in nanocarriers for EMO delivery and their anticancer applications. These carriers include liposomes, nanoparticles, polymeric micelles, nanogels, and others, with nanoparticle-based formulations being the most extensively explored. Nanoformulations encapsulating EMO have demonstrated promising therapeutic results against various cancers, particularly breast cancer, followed by liver and lung cancers. We systematically summarize the preparation methods, materials, and physicochemical properties of EMO-loaded nanopreparations, underscoring key findings on how nanotechnology improves the anticancer efficacy of EMO. This review provides valuable insights for researchers engaged in developing nano delivery systems for anticancer drugs.
{"title":"Advances in nano drug delivery systems for enhanced efficacy of emodin in cancer therapy","authors":"Zhenghao Ai , Bingyao Liu , Junyan Chen , Xinhao Zeng , Ke Wang , Chao Tao , Jing Chen , Liuxuan Yang , Qian Ding , Meiling Zhou","doi":"10.1016/j.ijpx.2024.100314","DOIUrl":"10.1016/j.ijpx.2024.100314","url":null,"abstract":"<div><div>Cancer remains one of the leading causes of death worldwide, highlighting the urgent need for novel antitumor drugs. Natural products have long been a crucial source of anticancer agents. Among these, emodin (EMO), a multifunctional anthraquinone compound, exhibits significant anticancer effects but is hindered in clinical applications by challenges such as low solubility, rapid metabolism, poor bioavailability, and off-target toxicity. Nano drug delivery systems offer effective strategies to overcome these limitations by enhancing the solubility, stability, bioavailability, and targeting ability of EMO. While substantial progress has been made in developing EMO-loaded nanoformulations, a comprehensive review on this topic is still lacking. This paper aims to fill this gap by providing an overview of recent advancements in nanocarriers for EMO delivery and their anticancer applications. These carriers include liposomes, nanoparticles, polymeric micelles, nanogels, and others, with nanoparticle-based formulations being the most extensively explored. Nanoformulations encapsulating EMO have demonstrated promising therapeutic results against various cancers, particularly breast cancer, followed by liver and lung cancers. We systematically summarize the preparation methods, materials, and physicochemical properties of EMO-loaded nanopreparations, underscoring key findings on how nanotechnology improves the anticancer efficacy of EMO. This review provides valuable insights for researchers engaged in developing nano delivery systems for anticancer drugs.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100314"},"PeriodicalIF":5.2,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005259","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 : 2024-12-17DOI: 10.1016/j.ijpx.2024.100311
Ebtsam A. Abdel-Wahab , Zahraa Haleem Al-Qaim , Ahmed T.H. Faris Al-Karkhi , Aysam M. Fayed , Ahmed M. Eldmrdash , Mohammed Abdalla Hussein , Amal Abdel-Aziz , Azza M. Metwaly , Heba.G. Abdelzaher , M.A. Abdelzaher , Diana A. ALsherif
<div><h3>Objectives</h3><div>Colorectal cancer is the third most common cancer worldwide, accounting for approximately 10 % of all cancer cases. It is also the second leading cause of cancer-related deaths globally. Phloretin is a natural compound found in apples and other fruits. It has been studied for its potential health benefits, including antioxidant and anti-inflammatory properties. However, more research is needed to fully understand its impact on cancer prevention or treatment. This article aimed to prepare phloretin-nanospanlastics (Ph-NSLs) to evaluate their effects on dimethylhydrazine (DMH)-induced colon cancer in mice.</div></div><div><h3>Methods</h3><div>Morphology, Particle size, zeta potential, UV–vis, entrapment efficiency, polydispersity index, FT-IR spectra, and drug release of phloretin and Ph-NSLs at pH 6.8.were described. Ph-NSLs were also tested for their anti-cancer properties in DMH-induced colon cancer in mice. A 36 mice were divided into 6 groups; Normal control, DMH (20 mg/k.g.b.w.), DMH + Ph-NSLs (25 mg/k.g.b.w.), DMH + Ph-NSLs (50 mg/k.g.b.w.), DMH + 5-FU(20 mg/k.g.b.w.), DMH + Ph-NSLs (50 mg), 5-FU (20 mg). Ph-NSLs were tested for their anticancer properties in DMH-treated mice by evaluating the IC50, viability and inhibitory values of Ph-NSLs against Caco-2. Also, the effect of Ph-NSLs administration on number of surviving mice, number of tumors/mice, average of tumor size, Hb, RBCs, WBCs, C19–9, MDA, GSH, SOD, IL-2, TNF-α, TGF-β1, CEA, and P53 levels in mice treated DMH were estimated.</div></div><div><h3>Results</h3><div>The synthesized Ph-NSLs were uniform, spherically shaped, and well dispersed, with a size, entrapment efficiency, and polydispersity index of approximately 114.06 ± 8.35 nm, 78.60 %, and 0.05, respectively. The zeta potential value of Ph-NSLs was measured at −21.5 ± 1.47 mV. Zeta potential reflects the surface charge of nanoparticles and affects their stability and interactions. UV spectra of phloretin and Ph-NSLs showed strong absorption peaks at 225 and 285 nm. These peaks correspond to specific wavelengths where the compound absorbs light. The percentage of Ph- NSLs release was found to be 56.87 ± 2.45 %. IC50 of Ph-NSLs was recorded 15.76 ± 0.42 μg/ml and the viability and inhibitory values of Ph-NSLs against Caco-2 cell lines was resorded 2.39, and 97.61 %, respectively at 100 μg/ml as well as 10.3, and 89.7 %, respectively at 50 μg/ml.</div><div>Moreover, The combination of 5-FU and Ph-NSLs resulted in a moderate increase in survival and significantly reduces tumor size and number, showing enhanced anticancer efficacy compared to individual treatments as well as attenuated levels of hemoglobin (Hb), red blood cells (RBCs), and white blood cells (WBCs). Reduced plasma cancer antigen 19–9 (CA19–9) levels as well as improved of colon malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), interleukine-2 (IL-2), tumor necrosis factor-alpha (TNF-α), tumor growth factor-bet
{"title":"Phloretin-nanospanlastics for targeting the Akt/PI3K signaling pathways in dimethylhydrazine-induced colon cancer in mice","authors":"Ebtsam A. Abdel-Wahab , Zahraa Haleem Al-Qaim , Ahmed T.H. Faris Al-Karkhi , Aysam M. Fayed , Ahmed M. Eldmrdash , Mohammed Abdalla Hussein , Amal Abdel-Aziz , Azza M. Metwaly , Heba.G. Abdelzaher , M.A. Abdelzaher , Diana A. ALsherif","doi":"10.1016/j.ijpx.2024.100311","DOIUrl":"10.1016/j.ijpx.2024.100311","url":null,"abstract":"<div><h3>Objectives</h3><div>Colorectal cancer is the third most common cancer worldwide, accounting for approximately 10 % of all cancer cases. It is also the second leading cause of cancer-related deaths globally. Phloretin is a natural compound found in apples and other fruits. It has been studied for its potential health benefits, including antioxidant and anti-inflammatory properties. However, more research is needed to fully understand its impact on cancer prevention or treatment. This article aimed to prepare phloretin-nanospanlastics (Ph-NSLs) to evaluate their effects on dimethylhydrazine (DMH)-induced colon cancer in mice.</div></div><div><h3>Methods</h3><div>Morphology, Particle size, zeta potential, UV–vis, entrapment efficiency, polydispersity index, FT-IR spectra, and drug release of phloretin and Ph-NSLs at pH 6.8.were described. Ph-NSLs were also tested for their anti-cancer properties in DMH-induced colon cancer in mice. A 36 mice were divided into 6 groups; Normal control, DMH (20 mg/k.g.b.w.), DMH + Ph-NSLs (25 mg/k.g.b.w.), DMH + Ph-NSLs (50 mg/k.g.b.w.), DMH + 5-FU(20 mg/k.g.b.w.), DMH + Ph-NSLs (50 mg), 5-FU (20 mg). Ph-NSLs were tested for their anticancer properties in DMH-treated mice by evaluating the IC50, viability and inhibitory values of Ph-NSLs against Caco-2. Also, the effect of Ph-NSLs administration on number of surviving mice, number of tumors/mice, average of tumor size, Hb, RBCs, WBCs, C19–9, MDA, GSH, SOD, IL-2, TNF-α, TGF-β1, CEA, and P53 levels in mice treated DMH were estimated.</div></div><div><h3>Results</h3><div>The synthesized Ph-NSLs were uniform, spherically shaped, and well dispersed, with a size, entrapment efficiency, and polydispersity index of approximately 114.06 ± 8.35 nm, 78.60 %, and 0.05, respectively. The zeta potential value of Ph-NSLs was measured at −21.5 ± 1.47 mV. Zeta potential reflects the surface charge of nanoparticles and affects their stability and interactions. UV spectra of phloretin and Ph-NSLs showed strong absorption peaks at 225 and 285 nm. These peaks correspond to specific wavelengths where the compound absorbs light. The percentage of Ph- NSLs release was found to be 56.87 ± 2.45 %. IC50 of Ph-NSLs was recorded 15.76 ± 0.42 μg/ml and the viability and inhibitory values of Ph-NSLs against Caco-2 cell lines was resorded 2.39, and 97.61 %, respectively at 100 μg/ml as well as 10.3, and 89.7 %, respectively at 50 μg/ml.</div><div>Moreover, The combination of 5-FU and Ph-NSLs resulted in a moderate increase in survival and significantly reduces tumor size and number, showing enhanced anticancer efficacy compared to individual treatments as well as attenuated levels of hemoglobin (Hb), red blood cells (RBCs), and white blood cells (WBCs). Reduced plasma cancer antigen 19–9 (CA19–9) levels as well as improved of colon malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), interleukine-2 (IL-2), tumor necrosis factor-alpha (TNF-α), tumor growth factor-bet","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100311"},"PeriodicalIF":5.2,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983440","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 : 2024-12-17DOI: 10.1016/j.ijpx.2024.100313
Eleonora Bianchi , Marco Ruggeri , Barbara Vigani , Carola Aguzzi , Silvia Rossi , Giuseppina Sandri
Thermoplastic polymers provide a versatile platform to mimic various aspects of physiological extracellular matrix properties such as chemical composition, stiffness, and topography for use in cell and tissue engineering applications. In this review, we provide a brief overview of the most promising thermoplastic polymers, and in particular the thermoplastic polyesters, such as poly(lactic acid), poly(glycolic acid), and polycaprolactone, and the thermoplastic elastomers, such as polyurethanes, polyhydroxyalkanoates, and poly(butyl cyanoacrylate). A particular focus has been made on the synthesis processes, the processability and the biocompatibility. We also discuss how these materials can be applied in tissue engineering, mimicking tissues' structure and function, and stimulate mesenchymal stem cells differentiation and mechanotransduction.
{"title":"Synthesis and use of thermoplastic polymers for tissue engineering purposes","authors":"Eleonora Bianchi , Marco Ruggeri , Barbara Vigani , Carola Aguzzi , Silvia Rossi , Giuseppina Sandri","doi":"10.1016/j.ijpx.2024.100313","DOIUrl":"10.1016/j.ijpx.2024.100313","url":null,"abstract":"<div><div>Thermoplastic polymers provide a versatile platform to mimic various aspects of physiological extracellular matrix properties such as chemical composition, stiffness, and topography for use in cell and tissue engineering applications. In this review, we provide a brief overview of the most promising thermoplastic polymers, and in particular the thermoplastic polyesters, such as poly(lactic acid), poly(glycolic acid), and polycaprolactone, and the thermoplastic elastomers, such as polyurethanes, polyhydroxyalkanoates, and poly(butyl cyanoacrylate). A particular focus has been made on the synthesis processes, the processability and the biocompatibility. We also discuss how these materials can be applied in tissue engineering, mimicking tissues' structure and function, and stimulate mesenchymal stem cells differentiation and mechanotransduction.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100313"},"PeriodicalIF":5.2,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978436","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 : 2024-12-16DOI: 10.1016/j.ijpx.2024.100315
Guangji Yang , Dongyan Ren , Tao Yu, Junfeng Fang
As a recently discovered form of regulated cell death, ferroptosis has attracted much attention in the field cancer therapy. However, achieving considerably enhanced efficacy is often restricted by the overexpression of endogenous glutathione (GSH) in tumor microenvironment (TME). In this work, we report a ferroptosis-inducing strategy of GSH depletion and reactive oxygen species (ROS) generation based on a biodegradable copper-doped calcium phosphate (CaP) with L-buthionine sulfoximine (BSO) loading (denoted as BSO@CuCaP-LOD, BCCL). BCCL was conducted by a biomineralization approach using lactate oxidases (LOD) as a bio-template to obtain Cu-doped CaP nanoparticles. Then, BSO was loaded to form BCCL nanoparticles with pH-responsive biodegradability to endow controlled release of Cu2+ and BSO in response to acidic TME. Benefiting from the catalytic performance of LOD, BCCL efficiently depletes the level of lactate in tumor, which can generate endogenous H2O2 for subsequent Fenton-like reaction. The Cu2+ and BSO intracellular GSH depletion followed by GSH-mediated Cu2+/Cu+ conversion, leading to the inhibition of glutathione peroxidase 4 (GPX4) and generation of •OH radicals via Cu+-mediated Fenton-like reaction. BCCL confers enhanced ferroptosis induction via intracellular LOD-induced H2O2 production, BSO-mediated GSH depletion, and Cu+-mediated ROS generation, leading to cause effective ferroptotic cell damage. As verified by in vitro and in vivo assays, the designed BCCL nanoplatform is highly biocompatible and exhibits superior anticancer therapy on uterine cervical carcinoma U14 tumor xenografts. This study, therefore, provides a biocompatible therapeutic platform that modulating the TME to enable intensive ROS generating efficacy and GSH depleting performance, as well as provides an innovative paradigm for achieving effective ferroptosis-based cancer therapy.
{"title":"Biodegradable copper-doped calcium phosphate nanoplatform enables tumor microenvironment modulations for amplified ferroptosis in cervical carcinoma treatment","authors":"Guangji Yang , Dongyan Ren , Tao Yu, Junfeng Fang","doi":"10.1016/j.ijpx.2024.100315","DOIUrl":"10.1016/j.ijpx.2024.100315","url":null,"abstract":"<div><div>As a recently discovered form of regulated cell death, ferroptosis has attracted much attention in the field cancer therapy. However, achieving considerably enhanced efficacy is often restricted by the overexpression of endogenous glutathione (GSH) in tumor microenvironment (TME). In this work, we report a ferroptosis-inducing strategy of GSH depletion and reactive oxygen species (ROS) generation based on a biodegradable copper-doped calcium phosphate (CaP) with L-buthionine sulfoximine (BSO) loading (denoted as BSO@CuCaP-LOD, BCCL). BCCL was conducted by a biomineralization approach using lactate oxidases (LOD) as a bio-template to obtain Cu-doped CaP nanoparticles. Then, BSO was loaded to form BCCL nanoparticles with pH-responsive biodegradability to endow controlled release of Cu<sup>2+</sup> and BSO in response to acidic TME. Benefiting from the catalytic performance of LOD, BCCL efficiently depletes the level of lactate in tumor, which can generate endogenous H<sub>2</sub>O<sub>2</sub> for subsequent Fenton-like reaction. The Cu<sup>2+</sup> and BSO intracellular GSH depletion followed by GSH-mediated Cu<sup>2+</sup>/Cu<sup>+</sup> conversion, leading to the inhibition of glutathione peroxidase 4 (GPX4) and generation of •OH radicals via Cu<sup>+</sup>-mediated Fenton-like reaction. BCCL confers enhanced ferroptosis induction via intracellular LOD-induced H<sub>2</sub>O<sub>2</sub> production, BSO-mediated GSH depletion, and Cu<sup>+</sup>-mediated ROS generation, leading to cause effective ferroptotic cell damage. As verified by in vitro and in vivo assays, the designed BCCL nanoplatform is highly biocompatible and exhibits superior anticancer therapy on uterine cervical carcinoma U14 tumor xenografts. This study, therefore, provides a biocompatible therapeutic platform that modulating the TME to enable intensive ROS generating efficacy and GSH depleting performance, as well as provides an innovative paradigm for achieving effective ferroptosis-based cancer therapy.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100315"},"PeriodicalIF":5.2,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983431","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 : 2024-12-15DOI: 10.1016/j.ijpx.2024.100312
Lan Cheng , Yanhua Zhang , Qian Xu , Zheng Li , Zulan Liu , Fangyin Dai
Systemic administration of methotrexate (MTX), widely regarded as one of the most effective treatments for psoriasis, poses significant challenges due to its high toxicity, limited solubility, and potential for adverse effects. Consequently, developing a topical form of MTX may offer a safer and more effective strategy for psoriasis management. Silk fibroin (SF), a protein-based biomacromolecule, has shown considerable promise as a nanocarrier for sustained and targeted drug delivery, owing to its exceptional physicochemical and biological properties. This study aimed to develop and characterize a novel drug delivery nanocarrier for MTX using SF nanoparticles modified with hyaluronic acid (HA) and to assess their potential for skin-targeted drug delivery with reduced transdermal permeation. The nanoparticles were thoroughly characterized, demonstrating a uniform particle size, high drug-loading capacity, pH sensitivity, and excellent slow-release properties. In vitro and in vivo experiments further indicated that these nanoparticles effectively reduced psoriasis-induced inflammatory responses, including erythema and scaling, by inhibiting keratinocyte proliferation and decreasing levels of pro-inflammatory cytokines. The inclusion of HA improved nanoparticle targeting, particularly through interactions with overexpressed CD44 proteins in psoriatic skin, resulting in enhanced methotrexate accumulation at the sites of inflammation and improved therapeutic efficacy. Our findings suggest that HA/SF nanoparticles loaded with MTX represent a promising, safe transdermal delivery system for the localized treatment of psoriasis.
{"title":"Hyaluronic acid/silk fibroin nanoparticles loaded with methotrexate for topical treatment of psoriasis","authors":"Lan Cheng , Yanhua Zhang , Qian Xu , Zheng Li , Zulan Liu , Fangyin Dai","doi":"10.1016/j.ijpx.2024.100312","DOIUrl":"10.1016/j.ijpx.2024.100312","url":null,"abstract":"<div><div>Systemic administration of methotrexate (MTX), widely regarded as one of the most effective treatments for psoriasis, poses significant challenges due to its high toxicity, limited solubility, and potential for adverse effects. Consequently, developing a topical form of MTX may offer a safer and more effective strategy for psoriasis management. Silk fibroin (SF), a protein-based biomacromolecule, has shown considerable promise as a nanocarrier for sustained and targeted drug delivery, owing to its exceptional physicochemical and biological properties. This study aimed to develop and characterize a novel drug delivery nanocarrier for MTX using SF nanoparticles modified with hyaluronic acid (HA) and to assess their potential for skin-targeted drug delivery with reduced transdermal permeation. The nanoparticles were thoroughly characterized, demonstrating a uniform particle size, high drug-loading capacity, pH sensitivity, and excellent slow-release properties. In vitro and in vivo experiments further indicated that these nanoparticles effectively reduced psoriasis-induced inflammatory responses, including erythema and scaling, by inhibiting keratinocyte proliferation and decreasing levels of pro-inflammatory cytokines. The inclusion of HA improved nanoparticle targeting, particularly through interactions with overexpressed CD44 proteins in psoriatic skin, resulting in enhanced methotrexate accumulation at the sites of inflammation and improved therapeutic efficacy. Our findings suggest that HA/SF nanoparticles loaded with MTX represent a promising, safe transdermal delivery system for the localized treatment of psoriasis.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100312"},"PeriodicalIF":5.2,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11722578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970801","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 : 2024-12-01DOI: 10.1016/j.ijpx.2024.100270
Sammar Fathy Elhabal , Shrouk A. Ghaffar , Raghda Hager , Nahla A. Elzohairy , Mohamed Mansour Khalifa , Passant M. Mohie , Rania A. Gad , Nasreen N. Omar , Mohammed H. Elkomy , Mohammad Ahmad Khasawneh , Nashwa Abdelaal
{"title":"RETRACTED: Development of thermosensitive hydrogel of Amphotericin-B and Lactoferrin combination-loaded PLGA-PEG-PEI nanoparticles for potential eradication of ocular fungal infections: In-vitro, ex-vivo and in-vivo studies","authors":"Sammar Fathy Elhabal , Shrouk A. Ghaffar , Raghda Hager , Nahla A. Elzohairy , Mohamed Mansour Khalifa , Passant M. Mohie , Rania A. Gad , Nasreen N. Omar , Mohammed H. Elkomy , Mohammad Ahmad Khasawneh , Nashwa Abdelaal","doi":"10.1016/j.ijpx.2024.100270","DOIUrl":"10.1016/j.ijpx.2024.100270","url":null,"abstract":"","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100270"},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141839249","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}
This paper presents a comprehensive investigation of the manufacturing of itraconazole (ITZ) amorphous solid dispersions (ASDs) with Kolllidon® VA64 (KVA64) using hot-melt extrusion (HME) and in-line process monitoring, employing a Quality by Design (QbD) approach. A sequential Design of Experiments (DoE) strategy was utilized to optimize the manufacturing process, with in-line UV–Vis spectroscopy providing real-time monitoring. The first DoE used a fractional factorial screening design to evaluate critical process parameters (CPPs), revealing that ITZ concentration had the most significant impact on the product quality attributes. The second DoE, employing a central composite design, explored the interactions between feed rate and screw speed, using torque and absorbance at 370 nm as responses to develop a design space. Validation studies confirmed process robustness across multiple days, with stable in-line UV–Vis spectra and consistent product quality using 30 % ITZ, 300 rpm, 150 °C and 7 g/min as the optimized process conditions. Theoretical and experimental analyses indicated that shifts in UV–Vis spectra at different ITZ concentrations were due to conformational changes in ITZ, which were confirmed through density functional theory (DFT) calculations and infrared spectroscopy. This work offers novel insights into the production and monitoring of ITZ-KVA64-ASDs, demonstrating that in-line UV–Vis spectroscopy is a powerful tool for real-time process monitoring and/or control.
{"title":"Optimizing extrusion processes and understanding conformational changes in itraconazole amorphous solid dispersions using in-line UV–Vis spectroscopy and QbD principles","authors":"Hetvi Triboandas , Mariana Bezerra , Juan Almeida , Matheus de Castro , Bianca Aloise Maneira Corrêa Santos , Walkiria Schlindwein","doi":"10.1016/j.ijpx.2024.100308","DOIUrl":"10.1016/j.ijpx.2024.100308","url":null,"abstract":"<div><div>This paper presents a comprehensive investigation of the manufacturing of itraconazole (ITZ) amorphous solid dispersions (ASDs) with Kolllidon® VA64 (KVA64) using hot-melt extrusion (HME) and in-line process monitoring, employing a Quality by Design (QbD) approach. A sequential Design of Experiments (DoE) strategy was utilized to optimize the manufacturing process, with in-line UV–Vis spectroscopy providing real-time monitoring. The first DoE used a fractional factorial screening design to evaluate critical process parameters (CPPs), revealing that ITZ concentration had the most significant impact on the product quality attributes. The second DoE, employing a central composite design, explored the interactions between feed rate and screw speed, using torque and absorbance at 370 nm as responses to develop a design space. Validation studies confirmed process robustness across multiple days, with stable in-line UV–Vis spectra and consistent product quality using 30 % ITZ, 300 rpm, 150 °C and 7 g/min as the optimized process conditions. Theoretical and experimental analyses indicated that shifts in UV–Vis spectra at different ITZ concentrations were due to conformational changes in ITZ, which were confirmed through density functional theory (DFT) calculations and infrared spectroscopy. This work offers novel insights into the production and monitoring of ITZ-KVA64-ASDs, demonstrating that in-line UV–Vis spectroscopy is a powerful tool for real-time process monitoring and/or control.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100308"},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748607","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 : 2024-12-01DOI: 10.1016/j.ijpx.2024.100305
Alanood S. Alfutaimani , Nouf K. Alharbi , Amirah S. Alahmari , Almaha A. Alqabbani , Abdulaziz M. Aldayel
Lipid nanoparticles (LNPs) have emerged as promising carriers for delivering therapeutic agents, including mRNA-based immunotherapies, in various biomedical applications. The use of LNPs allows for efficient delivery of drugs, resulting in enhanced targeted delivery to specific tissues or cells. These LNPs can be categorized into several types, including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, and lipid-polymer hybrid nanoparticles. The preparation of LNPs involves the manipulation of their structural, dimensional, compositional, and physical characteristics via the use of different methods in the industry. Lipids used to construct LNPs can also be derived from various biological sources, such as natural lipids extracted from plants, animals, or microorganisms. This review dives into the different types of LNPs and their preparation methods. More importantly, it discusses all possible biological sources that are known to supply lipids for the creation of LNPs. Natural lipid reservoirs have surfaced as promising sources for generating LNPs. The use of LNPs in drug delivery is expected to increase significantly in the coming years. Herein, we suggest some environmentally friendly and biocompatible sources that can produce lipids for future LNPs production.
{"title":"Exploring the landscape of Lipid Nanoparticles (LNPs): A comprehensive review of LNPs types and biological sources of lipids","authors":"Alanood S. Alfutaimani , Nouf K. Alharbi , Amirah S. Alahmari , Almaha A. Alqabbani , Abdulaziz M. Aldayel","doi":"10.1016/j.ijpx.2024.100305","DOIUrl":"10.1016/j.ijpx.2024.100305","url":null,"abstract":"<div><div>Lipid nanoparticles (LNPs) have emerged as promising carriers for delivering therapeutic agents, including mRNA-based immunotherapies, in various biomedical applications. The use of LNPs allows for efficient delivery of drugs, resulting in enhanced targeted delivery to specific tissues or cells. These LNPs can be categorized into several types, including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, and lipid-polymer hybrid nanoparticles. The preparation of LNPs involves the manipulation of their structural, dimensional, compositional, and physical characteristics via the use of different methods in the industry. Lipids used to construct LNPs can also be derived from various biological sources, such as natural lipids extracted from plants, animals, or microorganisms. This review dives into the different types of LNPs and their preparation methods. More importantly, it discusses all possible biological sources that are known to supply lipids for the creation of LNPs. Natural lipid reservoirs have surfaced as promising sources for generating LNPs. The use of LNPs in drug delivery is expected to increase significantly in the coming years. Herein, we suggest some environmentally friendly and biocompatible sources that can produce lipids for future LNPs production.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100305"},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748606","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号