Pub Date : 2025-02-08DOI: 10.1016/j.ejps.2025.107030
Bingbing Wu , Yiwen Tang , Liyuan Zhao , Yan Gao , Xi Shen , Shuyu Xiao , Sanqiao Yao , Huisheng Qi , Fuhai Shen
Silicosis is a pulmonary disease characterized by inflammation and progressive fibrosis. Previous studies have shown that polydatin (PD) has potential biological activity in key signaling pathways regulating inflammation and apoptosis. To investigate the effect of PD on rats with silicosis, this study used network pharmacology and molecular docking methods to determine the target of PD treatment for silicosis. The therapeutic effect of PD on silicosis was confirmed by measuring the lung injury score, hydroxyproline content, and mRNA expression levels of key targets. In addition, metagenomic sequencing and gas chromatography-mass spectrometry were used to determine the gut microbiota composition and targeted metabolomics analysis, respectively. The results showed that PD could inhibit the expression of inflammation-related indexes and apoptosis-related indexes at protein and mRNA levels. PD also regulates the diversity of the intestinal flora and the content of short-chain fatty acids. In conclusion, the current data suggest that PD has a protective effect against silica-induced lung injury and plays a protective role in regulating intestinal flora diversity and short-chain fatty acid levels through the gut-lung axis.
{"title":"Integrated network pharmacological analysis and multi-omics techniques to reveal the mechanism of polydatin in the treatment of silicosis via gut-lung axis","authors":"Bingbing Wu , Yiwen Tang , Liyuan Zhao , Yan Gao , Xi Shen , Shuyu Xiao , Sanqiao Yao , Huisheng Qi , Fuhai Shen","doi":"10.1016/j.ejps.2025.107030","DOIUrl":"10.1016/j.ejps.2025.107030","url":null,"abstract":"<div><div>Silicosis is a pulmonary disease characterized by inflammation and progressive fibrosis. Previous studies have shown that polydatin (PD) has potential biological activity in key signaling pathways regulating inflammation and apoptosis. To investigate the effect of PD on rats with silicosis, this study used network pharmacology and molecular docking methods to determine the target of PD treatment for silicosis. The therapeutic effect of PD on silicosis was confirmed by measuring the lung injury score, hydroxyproline content, and mRNA expression levels of key targets. In addition, metagenomic sequencing and gas chromatography-mass spectrometry were used to determine the gut microbiota composition and targeted metabolomics analysis, respectively. The results showed that PD could inhibit the expression of inflammation-related indexes and apoptosis-related indexes at protein and mRNA levels. PD also regulates the diversity of the intestinal flora and the content of short-chain fatty acids. In conclusion, the current data suggest that PD has a protective effect against silica-induced lung injury and plays a protective role in regulating intestinal flora diversity and short-chain fatty acid levels through the gut-lung axis.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"207 ","pages":"Article 107030"},"PeriodicalIF":4.3,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-07DOI: 10.1016/j.ejps.2025.107035
Kitti Göntér , Szabolcs László , Valéria Tékus , Ágnes Dombi , Katalin Fábián , Szilárd Pál , Gábor Pozsgai , Lajos Botz , Ödön Wagner , Erika Pintér , Zsófia Hajna
Objective
Pain is one of the major public health burdens worldwide, however, conventional analgesics are often ineffective. Capsaicin—the active compound of Capsicum species, being responsible for their pungency—has been part of traditional medicine long ago. Capsaicin is a natural agonist of the Transient Receptor Potential Vanilloid 1 receptor—localized on capsaicin-sensitive sensory neurons and strongly involved in pain transmission-, and has been in focus of analgesic drug research for many years. In this study, we aimed to develop a sustained release transdermal patch (transdermal therapeutic system, TTS) combining the advantages of low-concentration capsaicin and diclofenac embedded in an innovative structure, as well as to perform complex preclinical investigations of its analgesic effect.
Methods
Drug delivery properties of the TTS were investigated with Franz cell and flow-through cell tests. Analgesic effect of the TTS was examined in in vivo models of acute postoperative and inflammatory, chronic neuropathic and osteoarthritic pain.
Results
Modified silicone polymer matrix-based TTS containing low-concentration capsaicin and diclofenac has been developed, releasing both compounds according to zero-order kinetics. Moreover, capsaicin and diclofenac facilitated the liberation of each other. Combined TTS significantly reduced acute postoperative and inflammatory pain, as well as chronic neuropathic and osteoarthritic pain. Interestingly, in acute postoperative and chronic osteoarthritic pain, capsaicin prolonged and potentiated the pain-relieving effect of diclofenac.
Conclusions
New generation combined low-concentration capsaicin-diclofenac containing TTS can be an effective therapeutic tool in acute and chronic pain states involving neuropathic and inflammatory components.
{"title":"New generation capsaicin-diclofenac containing, silicon-based transdermal patch provides prolonged analgesic effect in acute and chronic pain models","authors":"Kitti Göntér , Szabolcs László , Valéria Tékus , Ágnes Dombi , Katalin Fábián , Szilárd Pál , Gábor Pozsgai , Lajos Botz , Ödön Wagner , Erika Pintér , Zsófia Hajna","doi":"10.1016/j.ejps.2025.107035","DOIUrl":"10.1016/j.ejps.2025.107035","url":null,"abstract":"<div><h3>Objective</h3><div>Pain is one of the major public health burdens worldwide, however, conventional analgesics are often ineffective. Capsaicin—the active compound of <em>Capsicum</em> species, being responsible for their pungency—has been part of traditional medicine long ago. Capsaicin is a natural agonist of the Transient Receptor Potential Vanilloid 1 receptor—localized on capsaicin-sensitive sensory neurons and strongly involved in pain transmission-, and has been in focus of analgesic drug research for many years. In this study, we aimed to develop a sustained release transdermal patch (transdermal therapeutic system, TTS) combining the advantages of low-concentration capsaicin and diclofenac embedded in an innovative structure, as well as to perform complex preclinical investigations of its analgesic effect.</div></div><div><h3>Methods</h3><div>Drug delivery properties of the TTS were investigated with Franz cell and flow-through cell tests. Analgesic effect of the TTS was examined in <em>in vivo</em> models of acute postoperative and inflammatory, chronic neuropathic and osteoarthritic pain.</div></div><div><h3>Results</h3><div>Modified silicone polymer matrix-based TTS containing low-concentration capsaicin and diclofenac has been developed, releasing both compounds according to zero-order kinetics. Moreover, capsaicin and diclofenac facilitated the liberation of each other. Combined TTS significantly reduced acute postoperative and inflammatory pain, as well as chronic neuropathic and osteoarthritic pain. Interestingly, in acute postoperative and chronic osteoarthritic pain, capsaicin prolonged and potentiated the pain-relieving effect of diclofenac.</div></div><div><h3>Conclusions</h3><div>New generation combined low-concentration capsaicin-diclofenac containing TTS can be an effective therapeutic tool in acute and chronic pain states involving neuropathic and inflammatory components.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"207 ","pages":"Article 107035"},"PeriodicalIF":4.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-06DOI: 10.1016/j.ejps.2025.107034
Hamoud Alotaibi , Taher Hatahet , Wafa’ T. Al-Jamal
Indocyanine green J-aggregate (IJA) is a promising photothermal (PTT) agent that has recently been utilised in preclinical studies for cancer diagnostics and treatment. The unique properties, such as the red-shift absorption band and longer wavelengths, are behind IJA's superior thermal stability compared to its monomeric ICG. Loading IJA into nanoparticles (NPs) has proven advantageous in enhancing its in vivo targeting of various cancer models. However, the loading of IJA into more complex lipids, such as lipid nanocapsules (LNCs) and solid lipid nanoparticles (SLNs), has not been reported. The present work focuses on investigations of the effect of formulation parameters on pre-formed IJA (p-IJA) stability and the formation of p-IJA-loaded LNCs and SLNs, thus enhancing their theranostic applications. We investigated the effect of the lipid shell of LNCs and the lipid core of SLN on p-IJA stability. Our findings demonstrated the significant role of lipophilic surfactants (Span 85) and a high-melting-point lipid core (sodium stearate) in enhancing the p-IJA ratio and heating capacity following loading into SLNs. More importantly, p-IJA-SLN enhanced the optical stability of p-IJA in a range of biological media, such as serum proteins, blood, and collagen. Furthermore, lyophilised p-IJA-SLNs were successfully obtained after long-term storage. Overall, p-IJA-loaded lipid NPs could provide a promising platform for various applications, including photoacoustic imaging, PTT, photodynamic therapy (PDT), and combination therapy with chemotherapeutics.
{"title":"Understanding the formulation parameters for engineering indocyanine green J-aggregate lipid nanocapsules and solid lipid nanoparticles as promising photothermal agents","authors":"Hamoud Alotaibi , Taher Hatahet , Wafa’ T. Al-Jamal","doi":"10.1016/j.ejps.2025.107034","DOIUrl":"10.1016/j.ejps.2025.107034","url":null,"abstract":"<div><div>Indocyanine green J-aggregate (IJA) is a promising photothermal (PTT) agent that has recently been utilised in preclinical studies for cancer diagnostics and treatment. The unique properties, such as the red-shift absorption band and longer wavelengths, are behind IJA's superior thermal stability compared to its monomeric ICG. Loading IJA into nanoparticles (NPs) has proven advantageous in enhancing its <em>in vivo</em> targeting of various cancer models. However, the loading of IJA into more complex lipids, such as lipid nanocapsules (LNCs) and solid lipid nanoparticles (SLNs), has not been reported. The present work focuses on investigations of the effect of formulation parameters on pre-formed IJA (p-IJA) stability and the formation of p-IJA-loaded LNCs and SLNs, thus enhancing their theranostic applications. We investigated the effect of the lipid shell of LNCs and the lipid core of SLN on p-IJA stability. Our findings demonstrated the significant role of lipophilic surfactants (Span 85) and a high-melting-point lipid core (sodium stearate) in enhancing the p-IJA ratio and heating capacity following loading into SLNs. More importantly, p-IJA-SLN enhanced the optical stability of p-IJA in a range of biological media, such as serum proteins, blood, and collagen. Furthermore, lyophilised p-IJA-SLNs were successfully obtained after long-term storage. Overall, p-IJA-loaded lipid NPs could provide a promising platform for various applications, including photoacoustic imaging, PTT, photodynamic therapy (PDT), and combination therapy with chemotherapeutics.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"207 ","pages":"Article 107034"},"PeriodicalIF":4.3,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-05DOI: 10.1016/j.ejps.2025.107033
Yuhan Guo , Hanyu Wang , Qiang Zhu , Ying Mao , Xiangce Wen , Xin Zhang , Shirui Mao , Huiya Yuan , Jian Guan
In the present study, enalapril (ENP) was taking as a potential co-former to fabricate co-amorphous system with lacidipine (LCDP). The ENP/LCDP co-amorphous system was firstly prepared with or without mesoporous SiO2 and characterized by DSC, XRD and SEM technologies. The potential molecular interactions were evaluated by FTIR spectrums. Furthermore, the dissolution and pharmacokinetics behavior of various formulations were also carried out. It was demonstrated that the completely co-amorphization was obtained at ENP/LCDP 2:1 molar ratio by the intermolecular interactions between ENP and LCDP. The ENP/LCDP co-amorphous system significantly improve the dissolution rate of LCDP and ENP respectively. Compared to the naked ENP/LCDP co-amorphous system, remarkable enhancement of dissolution rate and bioavailability of model drugs was observed by incorporated the co-amorphous system into mesoporous SiO2, and a superior physical stability was also observed after accelerated study. Raman mapping revealed that the less microstructure phase separation could be the main reason for the better stability in presence of mesoporous SiO2. In conclusion, ENP could be successfully used as a potential co-former to fabricate co-amorphous system with poorly water-soluble drugs and collaborates the co-amorphous with mesoporous SiO2 become a promising strategy to achieve stable amorphous formulation for further enhancement of dissolution rate and bioavailability.
{"title":"Exploration of enalapril-lacidipine co-amorphous system with superior dissolution, in vivo absorption and physical stability via incorporated into mesoporous silica","authors":"Yuhan Guo , Hanyu Wang , Qiang Zhu , Ying Mao , Xiangce Wen , Xin Zhang , Shirui Mao , Huiya Yuan , Jian Guan","doi":"10.1016/j.ejps.2025.107033","DOIUrl":"10.1016/j.ejps.2025.107033","url":null,"abstract":"<div><div>In the present study, enalapril (ENP) was taking as a potential co-former to fabricate co-amorphous system with lacidipine (LCDP). The ENP/LCDP co-amorphous system was firstly prepared with or without mesoporous SiO<sub>2</sub> and characterized by DSC, XRD and SEM technologies. The potential molecular interactions were evaluated by FTIR spectrums. Furthermore, the dissolution and pharmacokinetics behavior of various formulations were also carried out. It was demonstrated that the completely co-amorphization was obtained at ENP/LCDP 2:1 molar ratio by the intermolecular interactions between ENP and LCDP. The ENP/LCDP co-amorphous system significantly improve the dissolution rate of LCDP and ENP respectively. Compared to the naked ENP/LCDP co-amorphous system, remarkable enhancement of dissolution rate and bioavailability of model drugs was observed by incorporated the co-amorphous system into mesoporous SiO<sub>2</sub>, and a superior physical stability was also observed after accelerated study. Raman mapping revealed that the less microstructure phase separation could be the main reason for the better stability in presence of mesoporous SiO<sub>2</sub>. In conclusion, ENP could be successfully used as a potential co-former to fabricate co-amorphous system with poorly water-soluble drugs and collaborates the co-amorphous with mesoporous SiO<sub>2</sub> become a promising strategy to achieve stable amorphous formulation for further enhancement of dissolution rate and bioavailability.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"207 ","pages":"Article 107033"},"PeriodicalIF":4.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-04DOI: 10.1016/j.ejps.2025.107032
Zhenhua Hu , Xiao Xiao , Guiyun Zhang , Yuanyuan Li
Combination therapy, involving the concurrent use of multiple medications, has become crucial for managing complex diseases with diverse pathological mechanisms. Fixed-Dose Combinations (FDCs) are formulated to leverage the synergistic effects of multiple drugs, thereby enhancing therapeutic outcomes. However, conventional FDCs typically maintain therapeutic effects for only up to 24 h and require frequent dosing, which often results in patient non-compliance and inconsistent treatment responses, especially in chronic diseases. This highlights the urgent need for long-acting FDCs that can provide sustained drug release over extended periods—weeks, months, or even years—thereby reducing dosing frequency and enhancing patient adherence. Microspheres, with their ability to encapsulate and release multiple medications in predefined patterns, are highly advantageous for developing long-acting FDC drugs. This review emphasizes the increasing demand for long-acting FDC drugs that ensure sustained drug release, reduce dosing frequency, and ultimately improve patient adherence. We also highlight the potential of microsphere technology, which enables precise encapsulation and sustained release of multiple medications, as a promising approach for revolutionizing long-acting FDCs with enhanced therapeutic outcomes.
{"title":"Revolutionizing fixed-dose combinations with long-acting microsphere","authors":"Zhenhua Hu , Xiao Xiao , Guiyun Zhang , Yuanyuan Li","doi":"10.1016/j.ejps.2025.107032","DOIUrl":"10.1016/j.ejps.2025.107032","url":null,"abstract":"<div><div>Combination therapy, involving the concurrent use of multiple medications, has become crucial for managing complex diseases with diverse pathological mechanisms. Fixed-Dose Combinations (FDCs) are formulated to leverage the synergistic effects of multiple drugs, thereby enhancing therapeutic outcomes. However, conventional FDCs typically maintain therapeutic effects for only up to 24 h and require frequent dosing, which often results in patient non-compliance and inconsistent treatment responses, especially in chronic diseases. This highlights the urgent need for long-acting FDCs that can provide sustained drug release over extended periods—weeks, months, or even years—thereby reducing dosing frequency and enhancing patient adherence. Microspheres, with their ability to encapsulate and release multiple medications in predefined patterns, are highly advantageous for developing long-acting FDC drugs. This review emphasizes the increasing demand for long-acting FDC drugs that ensure sustained drug release, reduce dosing frequency, and ultimately improve patient adherence. We also highlight the potential of microsphere technology, which enables precise encapsulation and sustained release of multiple medications, as a promising approach for revolutionizing long-acting FDCs with enhanced therapeutic outcomes.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"207 ","pages":"Article 107032"},"PeriodicalIF":4.3,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-04DOI: 10.1016/j.ejps.2025.107031
Suqin Wang , Zeyu Huang , Lailai Zhou , Jiajia Li , Haihang Li , Tingting Jiang , Li Lin , Zhiqiang Zhang , Yuxia Fang , Ruzhi Zhang
Objective
To investigate the effects of recombinant human type XVII collagen (RHCXVII) on the proliferation and adhesion of primary human keratinocytes (HPKCs) and to observe its clinical efficacy and safety in bullous pemphigoid (BP).
Methods
The RHCXVII was produced by genetic recombination technology and characterized by Fourier transform infrared (FTIR) spectroscopy. HPKCs were obtained from human foreskin and seeded onto culture plates coated with RHCXVII at concentrations of 10, 50 and 100μg/ml. The proliferation and relative adhesion of HPKCs were assessed by Cell Counting Kit-8 (CCK-8) and adhesion assays, respectively. Trajectories and velocities of HPKCs were recorded using a living cell imaging platform. To assess the effects of RHCXVII on HPKCs, E-cadherin, integrinα6 and laminin α3 mRNA levels were measured using reverse transcription-polymerase chain reaction (RT-PCR) assays. The patient test sites were treated with RHCXVII, while the contralateral sides served as controls. This was performed in combination with systemic glucocorticoid treatment. Bilateral wound healing was recorded at various time points and the efficacy in BP was assessed.
Results
RHCXVII exhibited the anticipated structural characteristics of recombinant collagen and was deemed suitable for utilization in the present study. HPKCs demonstrated robust growth in culture plates precoated with RHCXVII, expressing keratin 15 (K15). After 3, 5 and 7 days, RHCXVII at a concentration of 10 µg/ml significantly promoted the proliferation of HPKCs (P<0.05). Furthermore, the optimal relative adhesion of HPKCs was observed when cells were cultured on RHCXVII at a concentration of 100 µg/ml (P<0.01). The mRNA levels of E-cadherin, integrinα6 and lamininα3 in HPKCs cultivated in wells coated with RHCXVII were considerably higher compared to the control group (P<0.05). The study encompassed a total of 12 patients. The mean time to resolution of lesions on the treated sides was 11.08 days, significantly shorter than the 13.42 days observed on the control sides. The mean time to blister resolution was 2.3 days shorter on the treated sides than on the controls. By day 7, the percentage improvement in wound healing compared to the baseline was 7.75 % greater on the treated sides than on the control sides. The study noted a high level of patient satisfaction and no occurrence of significant adverse events.
Conclusion
RHCXVII has the capacity to promote HPKC growth and adherence. In clinical applications, it has been demonstrated to accelerate wound healing in patients with bullous diseases (BD), thereby reducing the risk of subsequent secondary infection. Its potential as an adjunct treatment for wound repair in diseases such as BD merits further investigation.
{"title":"Therapeutic potential of recombinant human type XVII collagen in wound healing and bullous pemphigoid: From bench to bedside","authors":"Suqin Wang , Zeyu Huang , Lailai Zhou , Jiajia Li , Haihang Li , Tingting Jiang , Li Lin , Zhiqiang Zhang , Yuxia Fang , Ruzhi Zhang","doi":"10.1016/j.ejps.2025.107031","DOIUrl":"10.1016/j.ejps.2025.107031","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the effects of recombinant human type XVII collagen (RHCXVII) on the proliferation and adhesion of primary human keratinocytes (HPKCs) and to observe its clinical efficacy and safety in bullous pemphigoid (BP).</div></div><div><h3>Methods</h3><div>The RHCXVII was produced by genetic recombination technology and characterized by Fourier transform infrared (FTIR) spectroscopy. HPKCs were obtained from human foreskin and seeded onto culture plates coated with RHCXVII at concentrations of 10, 50 and 100μg/ml. The proliferation and relative adhesion of HPKCs were assessed by Cell Counting Kit-8 (CCK-8) and adhesion assays, respectively. Trajectories and velocities of HPKCs were recorded using a living cell imaging platform. To assess the effects of RHCXVII on HPKCs, E-cadherin, integrinα6 and laminin α3 mRNA levels were measured using reverse transcription-polymerase chain reaction (RT-PCR) assays. The patient test sites were treated with RHCXVII, while the contralateral sides served as controls. This was performed in combination with systemic glucocorticoid treatment. Bilateral wound healing was recorded at various time points and the efficacy in BP was assessed.</div></div><div><h3>Results</h3><div>RHCXVII exhibited the anticipated structural characteristics of recombinant collagen and was deemed suitable for utilization in the present study. HPKCs demonstrated robust growth in culture plates precoated with RHCXVII, expressing keratin 15 (K15). After 3, 5 and 7 days, RHCXVII at a concentration of 10 µg/ml significantly promoted the proliferation of HPKCs (<em>P<</em>0.05). Furthermore, the optimal relative adhesion of HPKCs was observed when cells were cultured on RHCXVII at a concentration of 100 µg/ml (<em>P</em><0.01). The mRNA levels of E-cadherin, integrinα6 and lamininα3 in HPKCs cultivated in wells coated with RHCXVII were considerably higher compared to the control group (<em>P</em><0.05). The study encompassed a total of 12 patients. The mean time to resolution of lesions on the treated sides was 11.08 days, significantly shorter than the 13.42 days observed on the control sides. The mean time to blister resolution was 2.3 days shorter on the treated sides than on the controls. By day 7, the percentage improvement in wound healing compared to the baseline was 7.75 % greater on the treated sides than on the control sides. The study noted a high level of patient satisfaction and no occurrence of significant adverse events.</div></div><div><h3>Conclusion</h3><div>RHCXVII has the capacity to promote HPKC growth and adherence. In clinical applications, it has been demonstrated to accelerate wound healing in patients with bullous diseases (BD), thereby reducing the risk of subsequent secondary infection. Its potential as an adjunct treatment for wound repair in diseases such as BD merits further investigation.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"207 ","pages":"Article 107031"},"PeriodicalIF":4.3,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143303553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.ejps.2024.106987
Ling Ye , XiangGuang Meng , Yan Zhan , Tong Li , Xin Huang , Hui Qiu , Jianzhu Zhou , Chengxian Guo
Background
Genetic variants in absorption, distribution, metabolism, and excretion (ADME) genes affect drug efficacy and side effects. Whole-exome sequencing (WES) effectively identifies these variants. Findings from Western populations may not apply to the Han Chinese population due to ethnic differences.
Objective
This study aimed to investigate genetic variants, metabolic phenotypes, and drug impacts related to ADME genes in the Han Chinese population using WES data.
Methods
ADME genes and drug profiles were sourced from multiple databases. WES data were collected from 357 samples at Third Xiangya Hospital and 5,000 samples from the “HuaBiao Project.” After WES, fastp was used for quality control; BWA, samtools, and the Picard software were used for comparison, sequencing, and de-duplication; GATK was used for base quality score recalibration; and variant quality score recalibration was carried out after detecting the variants, and the variants were annotated using ANNOVAR. ADME genes and drug profiles were obtained through PharmGKB and other databases, and then all variants in the exonic regions of ADME genes were extracted. The distributional characteristics of these variants, ethnic differences, and metabolic phenotype distribution of important ADME genes, such as CYP2B6, were analyzed. Prediction of deleterious variants of ADME gene employed the ADME gene variant prediction framework, and western blotting and enzyme assays were used to validate the impact of harmful variants.
Results
We integrated 604 ADME genes and 972 drugs. There were 33,925 single nucleotide polymorphisms (SNPs) and 484 insertion-deletions (InDels) in 5,357 Han Chinese WES samples; 88.9 % were rare. Of the SNPs, 60.9 % are new functional mutations in enzyme and transporter genes; InDels also affected these genes. We discovered Chinese-specific variants in key ADME genes and ethnic-specific metabolic phenotypes that could affect drug use. Finally, we screened 3,657 potentially harmful mutations; 45.6 % are novel. Western blotting and enzyme activity assays confirmed several harmful mutations significantly reduced CYP2C19 gene expression and function (P < 0.01).
{"title":"Research on genetic variant characteristics in ADME genes based on whole-exome sequencing in the Han Chinese population","authors":"Ling Ye , XiangGuang Meng , Yan Zhan , Tong Li , Xin Huang , Hui Qiu , Jianzhu Zhou , Chengxian Guo","doi":"10.1016/j.ejps.2024.106987","DOIUrl":"10.1016/j.ejps.2024.106987","url":null,"abstract":"<div><h3>Background</h3><div>Genetic variants in absorption, distribution, metabolism, and excretion (ADME) genes affect drug efficacy and side effects. Whole-exome sequencing (WES) effectively identifies these variants. Findings from Western populations may not apply to the Han Chinese population due to ethnic differences.</div></div><div><h3>Objective</h3><div>This study aimed to investigate genetic variants, metabolic phenotypes, and drug impacts related to ADME genes in the Han Chinese population using WES data.</div></div><div><h3>Methods</h3><div>ADME genes and drug profiles were sourced from multiple databases. WES data were collected from 357 samples at Third Xiangya Hospital and 5,000 samples from the “HuaBiao Project.” After WES, fastp was used for quality control; BWA, samtools, and the Picard software were used for comparison, sequencing, and de-duplication; GATK was used for base quality score recalibration; and variant quality score recalibration was carried out after detecting the variants, and the variants were annotated using ANNOVAR. ADME genes and drug profiles were obtained through PharmGKB and other databases, and then all variants in the exonic regions of ADME genes were extracted. The distributional characteristics of these variants, ethnic differences, and metabolic phenotype distribution of important ADME genes, such as CYP2B6, were analyzed. Prediction of deleterious variants of ADME gene employed the ADME gene variant prediction framework, and western blotting and enzyme assays were used to validate the impact of harmful variants.</div></div><div><h3>Results</h3><div>We integrated 604 ADME genes and 972 drugs. There were 33,925 single nucleotide polymorphisms (SNPs) and 484 insertion-deletions (InDels) in 5,357 Han Chinese WES samples; 88.9 % were rare. Of the SNPs, 60.9 % are new functional mutations in enzyme and transporter genes; InDels also affected these genes. We discovered Chinese-specific variants in key ADME genes and ethnic-specific metabolic phenotypes that could affect drug use. Finally, we screened 3,657 potentially harmful mutations; 45.6 % are novel. Western blotting and enzyme activity assays confirmed several harmful mutations significantly reduced CYP2C19 gene expression and function (<em>P</em> < 0.01).</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"205 ","pages":"Article 106987"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neuroinflammation is an undoubted hallmark of neurodegenerative processes characterized by memory impairment, loss of coordination and muscle strength in diseases such as Alzheimer's disease, Parkinson's disease and multiple sclerosis as well as depressive disorders. Cyclosporine A (CSA) has already been identified as a promising neuroprotective peptide, due to its well-known anti-inflammatory properties. Herein, CSA was encapsulated into α-tocopherol polyethylene glycol 1000 succinate (TPGS) micelles and intranasally administered to a lipopolysaccharide (LPS) induced mouse model of neuroinflammation. After the treatment, mice were subjected to behavioral tests to assess cognitive and motor skills, while the biodistribution of CSA in plasma and olfactory bulb was studied by a new HPLC method validated for precision and accuracy. The results highlighted that in comparison to the classic oral CSA suspension, the intranasal (IN) administration showed significatively better safety and efficiency profiles.
Notably, IN administration of CSA micelles showed relevant antidepressive effects and a certain ability to revert LPS-induced motor impairment.
This work pointed out that the innovative and noninvasive IN administration of TPGS micelles could represent a safe and effective alternative to the classic oral route to deliver CSA at the Central Nervous System level, where its beneficial activity against neuroinflammation can be exploited.
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Pub Date : 2025-02-01DOI: 10.1016/j.ejps.2024.106995
M.M. Szachniewicz , S.J.F. van den Eeden , K.E. van Meijgaarden , K.L.M.C. Franken , S. van Veen , A. Geluk , J.A. Bouwstra , T.H.M. Ottenhoff
Tuberculosis (TB) remains a significant global health challenge, latently affecting around a quarter of the global population. The sole licensed TB vaccine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), shows variable efficacy, particularly among adolescents and adults, underscoring the pressing need for more effective vaccination strategies. The administration route is crucial for vaccine efficacy, and administration via the skin, being rich in immune cells, may offer advantages over conventional subcutaneous routes, which lack direct access to abundant antigen-presenting cells.
This study compared the immunogenic effects of intradermal versus subcutaneous administration of a candidate TB vaccine delivering a Ag85B-ESAT6-Rv2034 (AER) multiphase fusion recombinant protein, in lipid-poly(D,L-lactic-co-glycolic acid) (lipid-PLGA) nanoparticles in mice. In-depth evaluation of immune responses in splenocytes was performed using 27-marker spectral flow cytometry. Both routes elicited significant T-cell responses. However, intradermal administration uniquely increased polyfunctional CD4+ and CD8+ T-cells producing IL-2, IFNγ, and TNFα, associated with protection against TB. Additionally, it significantly increased CD69+ B-cell counts and induced higher AER-specific antibody titers, particularly IgG2a. These results underscore the superior immunogenic potential of intradermal vaccine administration by effectively inducing immune cells associated with TB protection, highlighting its significance in the development of new vaccine strategies.
结核病仍然是一项重大的全球卫生挑战,潜在地影响着全球约四分之一的人口。唯一获得许可的结核病疫苗,牛分枝杆菌卡介苗(BCG),显示出不同的疗效,特别是在青少年和成人中,这强调了迫切需要更有效的疫苗接种战略。给药途径对疫苗效力至关重要,通过富含免疫细胞的皮肤给药,可能比传统的皮下给药途径更具优势,因为皮下给药途径无法直接接触到大量的抗原呈递细胞。本研究比较了在小鼠体内皮内注射和皮下注射一种提供Ag85B-ESAT6-Rv2034 (AER)多相融合重组蛋白(脂质-聚(D, l -乳酸-羟基乙酸)(脂质- plga)纳米颗粒的候选结核疫苗的免疫原性效果。利用27个标记物光谱流式细胞术对脾细胞的免疫反应进行了深入评估。这两种途径都引起了显著的t细胞反应。然而,皮内给药可惟一增加产生IL-2、IFNγ和TNFα的多功能CD4+和CD8+ t细胞,这与预防结核病有关。此外,它显著增加CD69+ b细胞计数,诱导更高的aer特异性抗体滴度,特别是IgG2a。这些结果强调了皮内接种疫苗通过有效诱导与结核病保护相关的免疫细胞而具有优越的免疫原性潜力,突出了其在开发新疫苗策略中的重要性。
{"title":"Intradermal versus subcutaneous immunization: Effects of administration route using a lipid-PLGA hybrid nanoparticle tuberculosis vaccine","authors":"M.M. Szachniewicz , S.J.F. van den Eeden , K.E. van Meijgaarden , K.L.M.C. Franken , S. van Veen , A. Geluk , J.A. Bouwstra , T.H.M. Ottenhoff","doi":"10.1016/j.ejps.2024.106995","DOIUrl":"10.1016/j.ejps.2024.106995","url":null,"abstract":"<div><div>Tuberculosis (TB) remains a significant global health challenge, latently affecting around a quarter of the global population. The sole licensed TB vaccine, <em>Mycobacterium bovis</em> Bacillus Calmette-Guérin (BCG), shows variable efficacy, particularly among adolescents and adults, underscoring the pressing need for more effective vaccination strategies. The administration route is crucial for vaccine efficacy, and administration via the skin, being rich in immune cells, may offer advantages over conventional subcutaneous routes, which lack direct access to abundant antigen-presenting cells.</div><div>This study compared the immunogenic effects of intradermal versus subcutaneous administration of a candidate TB vaccine delivering a Ag85B-ESAT6-Rv2034 (AER) multiphase fusion recombinant protein, in lipid-poly(D,L-lactic-co-glycolic acid) (lipid-PLGA) nanoparticles in mice. In-depth evaluation of immune responses in splenocytes was performed using 27-marker spectral flow cytometry. Both routes elicited significant T-cell responses. However, intradermal administration uniquely increased polyfunctional CD4<sup>+</sup> and CD8<sup>+</sup> T-cells producing IL-2, IFNγ, and TNFα, associated with protection against TB. Additionally, it significantly increased CD69<sup>+</sup> B-cell counts and induced higher AER-specific antibody titers, particularly IgG2a. These results underscore the superior immunogenic potential of intradermal vaccine administration by effectively inducing immune cells associated with TB protection, highlighting its significance in the development of new vaccine strategies.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"205 ","pages":"Article 106995"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}