This review looks at the pharmacokinetics, safety, and effectiveness of taletrectinib, a novel inhibitor that targets both ROS1 and NTRK, in patients with solid tumors and ROS1-positive non-small cell lung cancer (NSCLC). Objective response rates (ORR), progression-free survival (PFS), intracranial efficacy, and safety profiles are evaluated in the Review using phase I and phase II clinical trials, including both domestic and foreign research projects. Findings show that taletrectinib has a promising anticancer impact, good CNS penetration, and a solid safety record, especially in patients with brain metastases. These results imply that ROS1-positive cancers may benefit from taletrectinib as a treatment.
{"title":"Targeting ROS1 in NSCLC: Clinical Advances and Future Directions of Taletrectinib.","authors":"Manoj Kumbhare, Nishant Dattatray Pagere, Bhagwan Ide, Harshali Gode, Arshad Shaikh","doi":"10.62958/j.cjap.2025.025","DOIUrl":"https://doi.org/10.62958/j.cjap.2025.025","url":null,"abstract":"<p><p>This review looks at the pharmacokinetics, safety, and effectiveness of taletrectinib, a novel inhibitor that targets both ROS1 and NTRK, in patients with solid tumors and ROS1-positive non-small cell lung cancer (NSCLC). Objective response rates (ORR), progression-free survival (PFS), intracranial efficacy, and safety profiles are evaluated in the Review using phase I and phase II clinical trials, including both domestic and foreign research projects. Findings show that taletrectinib has a promising anticancer impact, good CNS penetration, and a solid safety record, especially in patients with brain metastases. These results imply that ROS1-positive cancers may benefit from taletrectinib as a treatment.</p>","PeriodicalId":23985,"journal":{"name":"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology","volume":"41 ","pages":"e20250025"},"PeriodicalIF":0.0,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145432312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In the context of dysbiosis, chronic inflammation, and carcinogenesis, non-Helicobacter pylori bacteria are becoming more widely acknowledged as significant contributors to stomach diseases. The stomach contains a variety of bacterial communities, including Fusobacterium nucleatum, Streptococcus species, Lactobacillus species, Prevotella species, Veillonella species, and Propionibacterium acnes, according to studies employing next-generation sequencing. Because of adaptation processes like urease activity, acid-tolerant metabolism, and biofilm development, these organisms can survive in acidic environments. While some, like Lactobacillus, can create metabolites like lactic acid that may impact carcinogenic nitrosation reactions, others, including F. nucleatum and Streptococcus, cause inflammation through immune activation and cytokine production. A known stomach carcinogen, N-nitroso compound, may be formed more frequently if nitrate-reducing bacteria proliferate. Following H. pylori eradication, dysbiosis frequently involves elevated abundance of these taxa, which may impact stomach cancer risk and mucosal integrity. The need for more comprehensive microbiome-targeted therapeutic approaches is highlighted by mounting evidence that non-H. pylori bacteria interact either antagonistically or synergistically with H. pylori and host factors, causing intestinal metaplasia, gastritis, and tumour progression, even though causality is still being investigated.
{"title":"The Role of Non-Helicobacter Pylori Bacteria in the Pathogenesis of Gastric Diseases.","authors":"Ruchi Tiwari, Gaurav Tiwari, Anshu Gupta, Vadivelan Ramachandran","doi":"10.62958/j.cjap.2025.027","DOIUrl":"https://doi.org/10.62958/j.cjap.2025.027","url":null,"abstract":"<p><p>In the context of dysbiosis, chronic inflammation, and carcinogenesis, non-Helicobacter pylori bacteria are becoming more widely acknowledged as significant contributors to stomach diseases. The stomach contains a variety of bacterial communities, including Fusobacterium nucleatum, Streptococcus species, Lactobacillus species, Prevotella species, Veillonella species, and Propionibacterium acnes, according to studies employing next-generation sequencing. Because of adaptation processes like urease activity, acid-tolerant metabolism, and biofilm development, these organisms can survive in acidic environments. While some, like Lactobacillus, can create metabolites like lactic acid that may impact carcinogenic nitrosation reactions, others, including F. nucleatum and Streptococcus, cause inflammation through immune activation and cytokine production. A known stomach carcinogen, N-nitroso compound, may be formed more frequently if nitrate-reducing bacteria proliferate. Following H. pylori eradication, dysbiosis frequently involves elevated abundance of these taxa, which may impact stomach cancer risk and mucosal integrity. The need for more comprehensive microbiome-targeted therapeutic approaches is highlighted by mounting evidence that non-H. pylori bacteria interact either antagonistically or synergistically with H. pylori and host factors, causing intestinal metaplasia, gastritis, and tumour progression, even though causality is still being investigated.</p>","PeriodicalId":23985,"journal":{"name":"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology","volume":"41 ","pages":"e20250027"},"PeriodicalIF":0.0,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145402213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-24DOI: 10.62958/j.cjap.2025.026
Sakshi Dnyaneshwar Khatale, Pravin Rangnath Dighe
Aim: To assess the theranostic potential of titanium nanoparticles (TiNPs), especially titanium dioxide nanoclusters, by assessing their distinct physicochemical characteristics and uses in biomedical domains as gene transport, immunotherapy, antimicrobial therapy, cancer, and biosensing.
Methods: The multifunctional properties of TiNPs were reviewed, with particular attention paid to their wide surface area, photo-reactivity, biocompatibility, and simplicity of surface modification. They were evaluated for use in drug delivery, photothermal and photodynamic therapy, biosensing, immunotherapy, gene therapy, antibacterial and antiviral activity, imaging (MRI, CT, fluorescence, optical, and photoacoustic imaging), and immunotherapy.
Result and discussion: TiNPs have been demonstrated to improve imaging accuracy and sensitivity while facilitating real-time therapy monitoring. Through targeted administration, they decreased systemic toxicity and increased therapeutic efficacy in oncology. Their production of reactive oxygen species (ROS) promotes their antiviral, antibacterial, and biofilm-inhibitory properties. TiNPs also make it easier to distribute checkpoint inhibitors for immunotherapy and to deliver genes through targeted uptake and electrostatic interactions. They also have high-resolution molecular imaging capabilities and perform better in biosensing and diagnostics.
Conclusion: By integrating therapeutic and diagnostic properties on one platform, titanium-based nanostructures demonstrate notable theranostic potential. The development of next-generation targeted medicines and diagnostics, better treatment results, and customized therapies are all made possible by their multifunctional nature.
{"title":"Titanium Nanoparticles in Theranostics: A Multifunctional Platform for Targeted Therapy and Advanced Diagnostics.","authors":"Sakshi Dnyaneshwar Khatale, Pravin Rangnath Dighe","doi":"10.62958/j.cjap.2025.026","DOIUrl":"10.62958/j.cjap.2025.026","url":null,"abstract":"<p><strong>Aim: </strong>To assess the theranostic potential of titanium nanoparticles (TiNPs), especially titanium dioxide nanoclusters, by assessing their distinct physicochemical characteristics and uses in biomedical domains as gene transport, immunotherapy, antimicrobial therapy, cancer, and biosensing.</p><p><strong>Methods: </strong>The multifunctional properties of TiNPs were reviewed, with particular attention paid to their wide surface area, photo-reactivity, biocompatibility, and simplicity of surface modification. They were evaluated for use in drug delivery, photothermal and photodynamic therapy, biosensing, immunotherapy, gene therapy, antibacterial and antiviral activity, imaging (MRI, CT, fluorescence, optical, and photoacoustic imaging), and immunotherapy.</p><p><strong>Result and discussion: </strong>TiNPs have been demonstrated to improve imaging accuracy and sensitivity while facilitating real-time therapy monitoring. Through targeted administration, they decreased systemic toxicity and increased therapeutic efficacy in oncology. Their production of reactive oxygen species (ROS) promotes their antiviral, antibacterial, and biofilm-inhibitory properties. TiNPs also make it easier to distribute checkpoint inhibitors for immunotherapy and to deliver genes through targeted uptake and electrostatic interactions. They also have high-resolution molecular imaging capabilities and perform better in biosensing and diagnostics.</p><p><strong>Conclusion: </strong>By integrating therapeutic and diagnostic properties on one platform, titanium-based nanostructures demonstrate notable theranostic potential. The development of next-generation targeted medicines and diagnostics, better treatment results, and customized therapies are all made possible by their multifunctional nature.</p>","PeriodicalId":23985,"journal":{"name":"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology","volume":"41 ","pages":"e20250026"},"PeriodicalIF":0.0,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145356189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-13DOI: 10.62958/j.cjap.2025.024
S Marakatham, Meruva Sathish Kumar, A Kavya, B Ramu, Prathibha Bharathi Mare
The RP-HPLC methodology was used to establish a straightforward, accurate, and precise method for estimating Lanadelumab. The following chromatographic conditions were used: 5. Mobile phase: 0.1% OPA buffer: Acetonitrile in a ratio of 65:35; 5. Stationary phase: Agilent C18 250 x 4.6 mm; 5. Detection wavelength: 228.0 nm; column temperature: 30 °C; diluent: 50:50 acetonitrile: water; retention time: 2.280 min. As the most efficient approach, conditions were finalized. The standard was injected six times to study the system appropriateness characteristics, and the results fell well within the acceptable range. An analysis of linearity was conducted at 25% to 150% levels, and the R2 score was 0.999. Standard precision was determined to be 0.8, whereas repeatable precision was found to be 0.5. 0.08µg/ml is the LOD, while 0.24µg/ml is the LOQ. The assay of the marketed formulation was conducted using the described method, and 100.14% was found.
{"title":"Degradation Studies and Method Development and Validation of Lanadelumab Using UV Detector in RP-HPLC.","authors":"S Marakatham, Meruva Sathish Kumar, A Kavya, B Ramu, Prathibha Bharathi Mare","doi":"10.62958/j.cjap.2025.024","DOIUrl":"10.62958/j.cjap.2025.024","url":null,"abstract":"<p><p>The RP-HPLC methodology was used to establish a straightforward, accurate, and precise method for estimating Lanadelumab. The following chromatographic conditions were used: 5. Mobile phase: 0.1% OPA buffer: Acetonitrile in a ratio of 65:35; 5. Stationary phase: Agilent C18 250 x 4.6 mm; 5. Detection wavelength: 228.0 nm; column temperature: 30 °C; diluent: 50:50 acetonitrile: water; retention time: 2.280 min. As the most efficient approach, conditions were finalized. The standard was injected six times to study the system appropriateness characteristics, and the results fell well within the acceptable range. An analysis of linearity was conducted at 25% to 150% levels, and the R2 score was 0.999. Standard precision was determined to be 0.8, whereas repeatable precision was found to be 0.5. 0.08µg/ml is the LOD, while 0.24µg/ml is the LOQ. The assay of the marketed formulation was conducted using the described method, and 100.14% was found.</p>","PeriodicalId":23985,"journal":{"name":"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology","volume":"41 ","pages":"e20250024"},"PeriodicalIF":0.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-10DOI: 10.62958/j.cjap.2025.023
Gaurav Tiwari, Ruchi Tiwari
Hemocyanin is dissolved freely in hemolymph, the invertebrate blood substitute, in contrast to haemoglobin, which is encased in red blood cells. When oxygenated, this pigment gives mollusc and arthropod blood its characteristic blue or purple hue. This review article delves into the fascinating biology of hemocyanin, the copper-based oxygen-carrying protein responsible for "purple blood" in many invertebrates, contrasting its characteristics with the more familiar iron-based hemoglobin. The review used a variety of sources from 2020 to 2025, including preprint sites (bioRxiv, medRxiv), grey literature/press-release outlets including EurekAlert! and ScienceDaily, PubMed, Embase, Scopus, Web of Science, BIOSIS, and Google Scholar. While hemocyanin's unique properties allow for adaptation to diverse environments, its direct application as an artificial human blood substitute faces significant biological and immunological hurdles. The report then transitions to a comprehensive overview of recent advancements in artificial human blood transfusion, focusing on hemoglobin-based oxygen carriers (HBOCs), perfluorocarbon-based oxygen carriers (PFCs), and stem cell-derived red blood cells. This analysis critically examines their development, clinical trial outcomes, and the persistent challenges in achieving safe, effective, and widely available blood alternatives, highlighting the distinct roles and limitations of hemocyanin-derived products primarily in immunomodulation rather than oxygen transport.
与包裹在红细胞中的血红蛋白不同,血青素可自由溶解于无脊椎动物的血液替代品——血淋巴中。当含氧时,这种色素使软体动物和节肢动物的血液呈现出特有的蓝色或紫色。这篇综述文章深入研究了令人着迷的血红蛋白生物学,这是一种铜基载氧蛋白,在许多无脊椎动物中负责“紫色血液”,并将其特征与更熟悉的铁基血红蛋白进行了对比。该综述使用了2020年至2025年的各种来源,包括预印本网站(bioRxiv, medRxiv),灰色文献/新闻稿渠道,包括EurekAlert!以及ScienceDaily、PubMed、Embase、Scopus、Web of Science、BIOSIS和谷歌Scholar。虽然血青素的独特特性使其能够适应不同的环境,但其作为人工血液替代品的直接应用面临着重大的生物学和免疫学障碍。然后,报告全面概述了人工输血方面的最新进展,重点是基于血红蛋白的氧载体(HBOCs)、基于全氟碳的氧载体(pfc)和干细胞来源的红细胞。本分析严格审查了它们的发展、临床试验结果,以及在实现安全、有效和广泛可用的血液替代品方面的持续挑战,强调了血青素衍生产品的独特作用和局限性,主要是在免疫调节中,而不是在氧运输中。
{"title":"Beyond Hemoglobin: A Review of Hemocyanin and the Biology of Purple Blood.","authors":"Gaurav Tiwari, Ruchi Tiwari","doi":"10.62958/j.cjap.2025.023","DOIUrl":"https://doi.org/10.62958/j.cjap.2025.023","url":null,"abstract":"<p><p>Hemocyanin is dissolved freely in hemolymph, the invertebrate blood substitute, in contrast to haemoglobin, which is encased in red blood cells. When oxygenated, this pigment gives mollusc and arthropod blood its characteristic blue or purple hue. This review article delves into the fascinating biology of hemocyanin, the copper-based oxygen-carrying protein responsible for \"purple blood\" in many invertebrates, contrasting its characteristics with the more familiar iron-based hemoglobin. The review used a variety of sources from 2020 to 2025, including preprint sites (bioRxiv, medRxiv), grey literature/press-release outlets including EurekAlert! and ScienceDaily, PubMed, Embase, Scopus, Web of Science, BIOSIS, and Google Scholar. While hemocyanin's unique properties allow for adaptation to diverse environments, its direct application as an artificial human blood substitute faces significant biological and immunological hurdles. The report then transitions to a comprehensive overview of recent advancements in artificial human blood transfusion, focusing on hemoglobin-based oxygen carriers (HBOCs), perfluorocarbon-based oxygen carriers (PFCs), and stem cell-derived red blood cells. This analysis critically examines their development, clinical trial outcomes, and the persistent challenges in achieving safe, effective, and widely available blood alternatives, highlighting the distinct roles and limitations of hemocyanin-derived products primarily in immunomodulation rather than oxygen transport.</p>","PeriodicalId":23985,"journal":{"name":"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology","volume":"41 ","pages":"e20250023"},"PeriodicalIF":0.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01DOI: 10.62958/j.cjap.2025.003
Apexa M Shah
Poorly soluble small compounds pose challenges in drug formulation due to low solubility, bioavailability, and therapeutic efficacy. These compounds often struggle to effectively target the disease due to their limited solubility. A large particle size further complicates reaching the desired site of action in the body. Reducing particle size through micronization or nanonization can enhance the efficacy of these active substances. Various methods, such as precipitation, milling, and high-pressure homogenization, are used to create nanocrystals, which can be delivered via multiple routes, with oral administration being preferred for safety and patient compliance. Nanonization is a key process in improving bioavailability, transforming micronized particles into nanoparticles under 1000 nm.
{"title":"Advancements in Pharmaceutical Nanocrystals:A Comprehensive Review.","authors":"Apexa M Shah","doi":"10.62958/j.cjap.2025.003","DOIUrl":"https://doi.org/10.62958/j.cjap.2025.003","url":null,"abstract":"<p><p>Poorly soluble small compounds pose challenges in drug formulation due to low solubility, bioavailability, and therapeutic efficacy. These compounds often struggle to effectively target the disease due to their limited solubility. A large particle size further complicates reaching the desired site of action in the body. Reducing particle size through micronization or nanonization can enhance the efficacy of these active substances. Various methods, such as precipitation, milling, and high-pressure homogenization, are used to create nanocrystals, which can be delivered via multiple routes, with oral administration being preferred for safety and patient compliance. Nanonization is a key process in improving bioavailability, transforming micronized particles into nanoparticles under 1000 nm.</p>","PeriodicalId":23985,"journal":{"name":"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology","volume":"41 ","pages":"e20250003"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmaceutical cocrystals have emerged as a transformative approach in drug development, enhancing the physicochemical properties of active pharmaceutical ingredients (APIs) such as solubility, bioavailability, stability, and dissolution rate without altering their pharmacological characteristics. Defined as multicomponent crystalline solids composed of two or more neutral molecules in a stoichiometric ratio, cocrystals are formed through non-ionic interactions like hydrogen bonding and π-π stacking. This review explores the evolution, design, preparation, and applications of pharmaceutical cocrystals, highlighting their ability to improve drug performance, enable controlled release, and offer intellectual property opportunities. Various preparation methods, including solvent-based (e.g., solvent evaporation, cooling crystallization) and solid-based (e.g., grinding, liquid-assisted grinding) techniques, are discussed alongside design approaches like hydrogen bonding propensity and the supramolecular synthonic approach. The review also addresses challenges such as molecular compatibility, thermodynamic barriers, and regulatory considerations. With regulatory acceptance from agencies like the FDA and ongoing advancements in crystal engineering, pharmaceutical cocrystals hold significant promise for optimizing drug delivery and formulation, necessitating further research to fully realize their potential in commercial applications.
{"title":"Pharmaceutical Cocrystals: A Review on Design, Preparation, Application and Challenges.","authors":"Suvarna Jagannath Shelke, Dhanashri Haushiram Bhangare, Mayuri Deepak Patil","doi":"10.62958/j.cjap.2025.022","DOIUrl":"https://doi.org/10.62958/j.cjap.2025.022","url":null,"abstract":"<p><p>Pharmaceutical cocrystals have emerged as a transformative approach in drug development, enhancing the physicochemical properties of active pharmaceutical ingredients (APIs) such as solubility, bioavailability, stability, and dissolution rate without altering their pharmacological characteristics. Defined as multicomponent crystalline solids composed of two or more neutral molecules in a stoichiometric ratio, cocrystals are formed through non-ionic interactions like hydrogen bonding and π-π stacking. This review explores the evolution, design, preparation, and applications of pharmaceutical cocrystals, highlighting their ability to improve drug performance, enable controlled release, and offer intellectual property opportunities. Various preparation methods, including solvent-based (e.g., solvent evaporation, cooling crystallization) and solid-based (e.g., grinding, liquid-assisted grinding) techniques, are discussed alongside design approaches like hydrogen bonding propensity and the supramolecular synthonic approach. The review also addresses challenges such as molecular compatibility, thermodynamic barriers, and regulatory considerations. With regulatory acceptance from agencies like the FDA and ongoing advancements in crystal engineering, pharmaceutical cocrystals hold significant promise for optimizing drug delivery and formulation, necessitating further research to fully realize their potential in commercial applications.</p>","PeriodicalId":23985,"journal":{"name":"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology","volume":"41 ","pages":"e20250022"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Intranasal delivery offers a promising route for direct drug transport to the central nervous system, bypassing the blood-brain barrier and improving therapeutic outcomes in neurodegenerative diseases like Alzheimer's disease. Donepezil, a widely prescribed drug for Alzheimer's, suffers from poor oral bioavailability, delayed onset, and limited nootropic activity due to extensive systemic metabolism. To address these limitations, this study aimed to develop and optimize a Donepezil-loaded lipid-based nanoemulsion for enhanced nose-to-brain delivery. A Box-Behnken Design (BBD) was employed to optimize three formulation variables: drug-to-lipid ratio (1:2 to 1:6), surfactant concentration (1-2% w/v), and stirring speed (1500-2500 rpm), with their effects assessed on particle size, drug entrapment efficiency, and drug loading. Based on solubility and hydrophilic-lipophilic balance, Glyceryl Monostearate and Tween 80 were selected as excipients. Seventeen formulations were prepared and analyzed using Response Surface Methodology. The optimized formulation (Batch 18) exhibited a particle size of 160.12 nm, entrapment efficiency of 80.75%, and drug loading of 19.98%, with a desirability score of 0.977. Predicted and observed values were within ±5% variation, confirming model reliability with high Adjusted R² (>0.95), Predicted R² (>0.90), and a non-significant lack of fit (p > 0.05) by ANOVA. The optimized nanoemulsion showed enhanced brain-targeting efficiency and improved nootropic potential of Donepezil via the intranasal route, presenting a promising strategy for Alzheimer's therapy. However, the study was limited to in vitro assessments, and further in vivo pharmacokinetic, pharmacodynamic, and long-term safety evaluations are warranted to comprehensively establish its therapeutic potential.
{"title":"Acetylcholinesterase Inhibitor-Based Nose‑to‑Brain Delivery of Donepezil‑Loaded Lipid Nanoemulsion for Alzheimer's Therapy.","authors":"Chandan Mohanty, Mahendrakumar R Dubey, Saswati Panigrahi, Shubham Singh, Sanjesh Rathi, Junmoni Nath","doi":"10.62958/j.cjap.2025.020","DOIUrl":"10.62958/j.cjap.2025.020","url":null,"abstract":"<p><p>Intranasal delivery offers a promising route for direct drug transport to the central nervous system, bypassing the blood-brain barrier and improving therapeutic outcomes in neurodegenerative diseases like Alzheimer's disease. Donepezil, a widely prescribed drug for Alzheimer's, suffers from poor oral bioavailability, delayed onset, and limited nootropic activity due to extensive systemic metabolism. To address these limitations, this study aimed to develop and optimize a Donepezil-loaded lipid-based nanoemulsion for enhanced nose-to-brain delivery. A Box-Behnken Design (BBD) was employed to optimize three formulation variables: drug-to-lipid ratio (1:2 to 1:6), surfactant concentration (1-2% w/v), and stirring speed (1500-2500 rpm), with their effects assessed on particle size, drug entrapment efficiency, and drug loading. Based on solubility and hydrophilic-lipophilic balance, Glyceryl Monostearate and Tween 80 were selected as excipients. Seventeen formulations were prepared and analyzed using Response Surface Methodology. The optimized formulation (Batch 18) exhibited a particle size of 160.12 nm, entrapment efficiency of 80.75%, and drug loading of 19.98%, with a desirability score of 0.977. Predicted and observed values were within ±5% variation, confirming model reliability with high Adjusted R² (>0.95), Predicted R² (>0.90), and a non-significant lack of fit (p > 0.05) by ANOVA. The optimized nanoemulsion showed enhanced brain-targeting efficiency and improved nootropic potential of Donepezil via the intranasal route, presenting a promising strategy for Alzheimer's therapy. However, the study was limited to in vitro assessments, and further in vivo pharmacokinetic, pharmacodynamic, and long-term safety evaluations are warranted to comprehensively establish its therapeutic potential.</p>","PeriodicalId":23985,"journal":{"name":"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology","volume":"41 ","pages":"e20250020"},"PeriodicalIF":0.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144875505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Monoclonal antibodies (mAbs) have witnessed significant advancements in recent years, offering promising therapeutic options for the management of complex and multifactorial diseases. Despite their success, conventional mAbs exhibit limitations such as restricted targeting capacity and suboptimal immune activation, which has driven the development of bispecific monoclonal antibodies (BsAbs) capable of engaging multiple antigens simultaneously. Among these, CD3-bispecific mAbs have emerged as a potent class of immunotherapeutics, capable of activating T cells and inducing T cell-mediated cytotoxicity against target cells, particularly in cancer immunotherapy. This review highlights several representative formats of BsAbs, elucidates their underlying mechanisms of action, and discusses current design strategies for CD3-bispecific mAbs. Emphasis is placed on optimizing their therapeutic efficacy while minimizing adverse effects, supported by recent drug development examples and clinical applications.
{"title":"CD3-Bispecific Monoclonal Antibodies: A Novel Therapeutic Approach for Complex and Multifactorial Diseases.","authors":"Shubham Singh, Sanjesh Rathi, Sakshi Singh, Bhawna Sharma, Vivek Dwivedi","doi":"10.62958/j.cjap.2025.019","DOIUrl":"https://doi.org/10.62958/j.cjap.2025.019","url":null,"abstract":"<p><p>Monoclonal antibodies (mAbs) have witnessed significant advancements in recent years, offering promising therapeutic options for the management of complex and multifactorial diseases. Despite their success, conventional mAbs exhibit limitations such as restricted targeting capacity and suboptimal immune activation, which has driven the development of bispecific monoclonal antibodies (BsAbs) capable of engaging multiple antigens simultaneously. Among these, CD3-bispecific mAbs have emerged as a potent class of immunotherapeutics, capable of activating T cells and inducing T cell-mediated cytotoxicity against target cells, particularly in cancer immunotherapy. This review highlights several representative formats of BsAbs, elucidates their underlying mechanisms of action, and discusses current design strategies for CD3-bispecific mAbs. Emphasis is placed on optimizing their therapeutic efficacy while minimizing adverse effects, supported by recent drug development examples and clinical applications.</p>","PeriodicalId":23985,"journal":{"name":"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology","volume":"41 ","pages":"e20250019"},"PeriodicalIF":0.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144776330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-09DOI: 10.62958/j.cjap.2025.018
Vrushali P Patole, Nirmala V Shinde, Siddhi M Chandak, Ashwini T Satalkar
Introduction: Cancer remains a major global health concern, accounting for nearly 10 million deaths annually. Despite its complexity and heterogeneity, significant advancements in cancer research over the past two decades have transformed the landscape of cancer diagnosis, treatment, and prevention. Notably, the integration of personalized medicine and technological innovations has led to more precise, effective, and individualized care strategies.
Materials: This review utilized peer-reviewed articles, clinical trial data, and recent meta-analyses published between 2015 and 2025. Major databases including PubMed, Scopus, and Web of Science were searched using keywords such as "cancer therapy," "personalized medicine," "cancer diagnostics," "immunotherapy," and "cancer prevention.
Methods: A systematic review approach was applied, focusing on studies that reported significant advancements in cancer treatment modalities (e.g., targeted therapy, immunotherapy), diagnostic technologies (e.g., liquid biopsy, AI-based imaging), and preventive strategies (e.g., vaccination, genetic screening). Articles were selected based on relevance, impact, and recency, with a preference for clinical studies and high-impact reviews.
Results: Emerging therapies such as immune checkpoint inhibitors, CAR-T cell therapy, and molecularly targeted agents have shown improved survival and response rates in several cancer types. Diagnostic innovations, including next-generation sequencing and non-invasive liquid biopsies, have enhanced early detection and monitoring of treatment response. Preventive measures, such as HPV and HBV vaccination and genetic risk profiling, have reduced the incidence of several preventable cancers. Personalized medicine approaches have enabled treatment decisions based on individual genetic and molecular profiles, leading to improved therapeutic outcomes and reduced adverse effects.
Discussion: The integration of genomics, artificial intelligence, and immunotherapy into oncology practice marks a shift toward precision medicine. While these advances have significantly improved patient care, challenges such as treatment resistance, access disparities, and the high cost of novel therapies remain. Continued interdisciplinary research, equitable healthcare policies, and investment in emerging technologies are essential to fully realize the benefits of modern cancer care.
导言:癌症仍然是一个主要的全球健康问题,每年造成近1000万人死亡。尽管癌症具有复杂性和异质性,但在过去二十年中,癌症研究取得了重大进展,改变了癌症诊断、治疗和预防的格局。值得注意的是,个性化医疗和技术创新的结合导致了更精确、有效和个性化的护理策略。材料:本综述利用了同行评议的文章、临床试验数据和2015年至2025年间发表的近期荟萃分析。主要数据库包括PubMed、Scopus和Web of Science,搜索关键词包括“癌症治疗”、“个性化医疗”、“癌症诊断”、“免疫治疗”和“癌症预防”。方法:采用系统综述方法,重点关注在癌症治疗方式(如靶向治疗、免疫治疗)、诊断技术(如液体活检、基于人工智能的成像)和预防策略(如疫苗接种、基因筛查)方面取得重大进展的研究。文章的选择基于相关性、影响和近时性,优先考虑临床研究和高影响的综述。结果:免疫检查点抑制剂、CAR-T细胞疗法和分子靶向药物等新兴疗法已经显示出在几种癌症类型中提高了生存率和应答率。诊断创新,包括下一代测序和非侵入性液体活检,加强了早期发现和监测治疗反应。预防措施,如人乳头瘤病毒和乙型肝炎病毒疫苗接种和遗传风险分析,减少了几种可预防癌症的发病率。个性化医疗方法使得基于个体遗传和分子谱的治疗决策成为可能,从而改善了治疗效果,减少了不良反应。讨论:将基因组学、人工智能和免疫疗法整合到肿瘤实践中,标志着精准医学的转变。虽然这些进展显著改善了患者护理,但诸如治疗耐药性、可及性差异和新疗法的高成本等挑战仍然存在。持续的跨学科研究、公平的医疗政策和对新兴技术的投资对于充分实现现代癌症治疗的好处至关重要。
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