{"title":"Exploration of medicinal plants as potential therapeutics against COVID-19: molecular insights and drug development prospects with other significant medicinal information a retrospective exposition.","authors":"Saurabh Dilip Bhandare","doi":"10.1093/jpp/rgae074","DOIUrl":"10.1093/jpp/rgae074","url":null,"abstract":"<p><strong>Objectives: </strong>The study aims to explore the potential of medicinal plants and their phytoconstituents as effective inhibitors of the coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus. The focus is on investigating specific medicinal plants known for their pharmacological properties, such as: antioxidant, anti-inflammatory, and immunomodulatory effects, to determine their viability in developing COVID-19 treatments.</p><p><strong>Materials and methods: </strong>This study involves a comprehensive study of medicinal plants, including: Withania somnifera (Ashwagandha) and Ocimum sanctum (Holy Basil), known for their beneficial health effects. Molecular docking studies were conducted to assess the interactions between phytoconstituents from these plants and SARS-CoV-2 proteins. The compounds' drug-like characteristics and safety profiles were also evaluated to determine their potential as therapeutic agents.</p><p><strong>Results: </strong>The molecular docking studies revealed that the phytoconstituents from the studied medicinal plants exhibit favourable interactions with SARS-CoV-2 proteins, suggesting their potential as therapeutic targets. These compounds demonstrated promising drug-like characteristics and safety profiles, indicating their suitability for further development as COVID-19-fighting medications.</p><p><strong>Discussion: </strong>The results indicate that medicinal plants and their bioactive substances hold significant potential for developing therapies against COVID-19. The ability of these organic substances to interact with key viral proteins and provide various therapeutic benefits highlights their potential as multi-functional treatment options. However, further research is necessary to confirm these findings and to understand the full scope of their therapeutic efficacy and safety in clinical settings.</p><p><strong>Conclusions: </strong>Medicinal plants and their phyto-constituents represent a promising avenue for developing effective treatments for COVID-19. The favourable interactions with SARS-CoV-2 proteins and the promising drug-like characteristics observed in this study suggest that these natural compounds could be integral in the fight against the COVID-19 pandemic. Further research and clinical trials are essential to fully validating their potential and translating these findings into practical medical applications.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"18-31"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oladapo F Fagbohun, Amanda Rollins, Lindsey Mattern, Kendra Cipollini, Hp Vasantha Rupasinghe
{"title":"Frondoside A of Cucumaria frondosa (Gennerus, 1767): Chemistry, biosynthesis, medicinal applications, and mechanism of actions.","authors":"Oladapo F Fagbohun, Amanda Rollins, Lindsey Mattern, Kendra Cipollini, Hp Vasantha Rupasinghe","doi":"10.1093/jpp/rgae059","DOIUrl":"10.1093/jpp/rgae059","url":null,"abstract":"<p><p>Cucumaria frondosa (Gennerus, 1767) or orange-footed sea cucumbers are traditional food and are used as natural sources of anti-diabetic, anti-inflammatory, antioxidant, anti-angiogenic, antimicrobial, and anticancer agents. Currently, the introduction of value-added sea cucumber products to the global market has inspired basic research on frondoside A and other saponins in sea cucumbers. These saponins serve as a means of their chemical defence. However, recent studies revealed that exposure to these saponins can lead to irritating symptoms from aerosolization of various holothurins. Moreover, extraction methods are critical to the bioavailability of various bioactive compounds found in sea cucumbers. Therefore, we have critically reviewed recent studies on the chemistry, biosynthesis, and pharmacological properties of frondoside A. Furthermore, the mechanism of actions of frondoside A was postulated and further studies are required for applications in functional foods, nutraceuticals, and pharmaceuticals. Frondoside A was first discovered from Cucumaria frondosa, and it is involved in protein kinase (PI3K/AKT/ERK1/2/p38 MAPK, RAC/CDC42 PAK1, NFκB/MAPK/JNK, and LXR-β) signalling pathways. It is also involved in the suppression of MYC oncogene transcriptional factors implicated and upregulated in over 70% of cancer types. Future research needs to be aimed at optimized green extraction techniques, efficient delivery methods, safety, and efficacy.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"32-42"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pharmacological investigation of genistein for its therapeutic potential against nitroglycerin-induced migraine headache.","authors":"Qirrat Sajjad, Arif-Ullah Khan, Aslam Khan","doi":"10.1093/jpp/rgae084","DOIUrl":"10.1093/jpp/rgae084","url":null,"abstract":"<p><strong>Objectives: </strong>Migraine, typically occurs on one side of the head, lasts for hours to days. Trigemino-vascular system (TVS) plays a vital role in pain generation, with neurogenic inflammation and oxidative stress playing key roles in its pathophysiology.</p><p><strong>Methods: </strong>This study aimed to investigate genistein's potential as anti-inflammatory and anti-oxidant agent in mitigating migraine pain. Genistein (20 and 50 mg/kg) was administered intraperitoneally (IP) to nitroglycerin (NTG; 10 mg/kg)-induced migraine model in rats. Behavioral analysis, antioxidant assay, immunohistochemistry (IHC), histopathological examination, ELISA, and RT-PCR were conducted to evaluate the antimigraine potential of genistein.</p><p><strong>Key findings: </strong>In-silico analysis showed genestien's ACE values of -4.8 to -9.2 Kcal/mol against selected protein targets. Genistein significantly reversed mechanical and thermal nociception, light phobicity, and head scratching; increased the intensities of GST, GSH, catalase; and down regulated lipid peroxidase (LPO) in cortex and trigeminal nucleus caudalis (TNC). It also reduced Nrf2, NF-kB, and IL6 expression, analyzed through IHC, improved histopathological features, and increased COX-2 and decreased PPAR-γ expressions, while RT-PCR analysis revealed increased PPAR-γ expressions in genistein-treated rats.</p><p><strong>Conclusion: </strong>Genistein exhibited potent antioxidant and anti-inflammatory properties in migraine treatment, acting through multifactorial mechanisms by modulating the expression of numerous proteins in the region cortex and TNC.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"76-94"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daiane Cristina de Assis Braga, Marcos Adriano Carlos Batista, Renata Guerra-Sá, Thayane Christine Alves da Silva, Marco Antônio Alves Carneiro, Maria Célia da Silva Lanna, Vasco Ariston Azevedo, Rodrigo Dias de Oliveira Carvalho, Gustavo Henrique Bianco de Souza, Vagner Roberto Antunes, Sandra Aparecida Lima de Moura, Carla Speroni Ceron, Leonardo Máximo Cardoso
{"title":"Psidium guajava leaves extract alters colonic microbiome composition and reduces intestinal sodium absorption in rats exposed to a high-sodium diet.","authors":"Daiane Cristina de Assis Braga, Marcos Adriano Carlos Batista, Renata Guerra-Sá, Thayane Christine Alves da Silva, Marco Antônio Alves Carneiro, Maria Célia da Silva Lanna, Vasco Ariston Azevedo, Rodrigo Dias de Oliveira Carvalho, Gustavo Henrique Bianco de Souza, Vagner Roberto Antunes, Sandra Aparecida Lima de Moura, Carla Speroni Ceron, Leonardo Máximo Cardoso","doi":"10.1093/jpp/rgae137","DOIUrl":"10.1093/jpp/rgae137","url":null,"abstract":"<p><strong>Objectives: </strong>High sodium intake is a major risk factor for hypertension and renal diseases. Previous studies have shown that a suspension of ethanolic extract of Psidium guajava (guava) leaves (PsE) has antihypertensive effects in rats on a high-sodium diet (HSD), but some mechanisms to that remain unexplored. This study explored whether oral PsE treatment affects sodium handling by the intestine and alters the gut microbiome in HSD-fed rats.</p><p><strong>Methods: </strong>Male Wistar rats were divided into two groups: standard salt diet (SSD) and HSD (0.9% Na+), from weaning. After 12 weeks, both groups received PsE (200 mg/kg) or a vehicle for an additional 4 weeks.</p><p><strong>Key findings: </strong>Sodium excretion was measured using flame photometry, and sodium absorption was assessed by intestinal perfusion technique. The gut microbiome was analysed through 16S ribosomal gene sequencing. HSD increased faecal sodium, further elevated by PsE, which inhibited intestinal sodium absorption in HSD rats. HSD altered the abundance of specific bacterial families, which PsE partially reversed. No changes in alpha diversity were noted among groups.</p><p><strong>Conclusions: </strong>These findings suggest that PsE inhibited intestinal sodium handling and that PsE, combined with increased faecal sodium, may reshape the gut microbiome of HSD rats to resemble that of SSD rats.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"111-126"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Angel George, Anns Mariya, Manu Eappen, Marimuthu Karthikeyan, Ravindranath Sreenath
{"title":"Serum autotaxin level: a promising diagnostic biomarker in differentiating Graves' disease and thyroiditis.","authors":"Angel George, Anns Mariya, Manu Eappen, Marimuthu Karthikeyan, Ravindranath Sreenath","doi":"10.1093/jpp/rgae073","DOIUrl":"10.1093/jpp/rgae073","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have suggested that serum autotaxin (ATX) may be a promising diagnostic biomarker in differentiating between Graves' disease (GD) and thyroiditis, as well as serving as a monitoring biomarker for GD. This study will evaluate the use of serum ATX as a diagnostic biomarker in these conditions.</p><p><strong>Methods: </strong>In this prospective interventional study, blood samples were collected from the patients who met both inclusion and exclusion criteria, and serum ATX levels were measured by using the MyBioSource human Autotaxin ELISA kit.</p><p><strong>Results: </strong>A total of 32 patients were enrolled, of which 18.8% were newly diagnosed with GD, 21.9% were thyroiditis, and 59.3% were on treatment for GD. Serum autotaxin antigen was significantly higher in GD patients than in thyroiditis (603.3217 ± 444.24 v/s 214.74 ± 55.91, P = <.005). Serum ATX measurement successfully discriminated GD patients from thyroiditis (AUC = 0.952, 95%CI: 0.00-1.00) with an optimal cutoff value of ≥257.20 ng/L (sensitivity = 100 and specificity = 81.71). Monitoring the efficacy of serum ATX was analyzed and showed a significant difference.</p><p><strong>Conclusion: </strong>The serum ATX was higher in subjects with GD as compared to thyroiditis, and ATX levels were found to be decreased during the treatment period. In conclusion, serum ATX can be used as a diagnostic and monitoring biomarker in GD.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"56-63"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhimin Shi, Rui Wang, Jie Huang, Qian Qian, Menglin Hu, Hengguo Zhang, Linfei Feng, Hao Gu, Yuanyin Wang
{"title":"Super-enhancer-driven ameboidal-type cell migration-related MMP14 expression in tongue squamous cell carcinoma switched by BATF and ATF3.","authors":"Zhimin Shi, Rui Wang, Jie Huang, Qian Qian, Menglin Hu, Hengguo Zhang, Linfei Feng, Hao Gu, Yuanyin Wang","doi":"10.1093/jpp/rgae063","DOIUrl":"10.1093/jpp/rgae063","url":null,"abstract":"<p><strong>Background: </strong>Tongue squamous cell carcinoma (TSCC) exhibits an aggressive biological behavior of lymph node and distant metastasis, which contributes to poorer prognosis and results in tongue function loss or death. In addition to known regulators and pathways of cell migration in TSCC, it is important to uncover pivotal switches governing tumor metastasis.</p><p><strong>Methods: </strong>Cancer cell migration-associated transcriptional and epigenetic characteristics were profiled in TSCC, and the specific super-enhancers (SEs) were identified. Molecular function and mechanism studies were used to investigate the pivotal switches in TSCC metastasis.</p><p><strong>Results: </strong>Ameboidal-type cell migration-related genes accompanied by transcriptional and epigenetic activity were enriched in TSCC. Meanwhile, the higher-ranked SE-related genes showed significant differences between 43 paired tumor and normal samples from the TCGA TSCC cohort. In addition, key motifs were detected in SE regions, and transcription factor-related expression levels were significantly associated with TSCC survival status. Notably, BATF and ATF3 regulated the expression of ameboidal-type cell migration-related MMP14 by switching the interaction with the SE region.</p><p><strong>Conclusion: </strong>SEs and related key motifs transcriptional regulate tumor metastasis-associated MMP14 and might be potential therapeutic targets for TSCC.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"64-75"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shaimaa R Ahmed, Ambreen Malik Uttra, Muhammad Usman, Sumera Qasim, Shah Jahan, Muhammad Roman, Hanan Khojah, Omnia Hendawy, Eman K Rashwan
{"title":"Deciphering farnesol's anti-arthritic and immunomodulatory potential by targeting multiple pathways: a combination of network pharmacology guided exploration and experimental verification.","authors":"Shaimaa R Ahmed, Ambreen Malik Uttra, Muhammad Usman, Sumera Qasim, Shah Jahan, Muhammad Roman, Hanan Khojah, Omnia Hendawy, Eman K Rashwan","doi":"10.1093/jpp/rgae126","DOIUrl":"10.1093/jpp/rgae126","url":null,"abstract":"<p><strong>Objective: </strong>Farnesol (FAR), a sesquiterpene alcohol, has documented FAR's anti-inflammatory and antioxidant activities. Current study was undertaken to assess the efficacy and mechanism of FAR in arthritis by employing network pharmacology and experimental models.</p><p><strong>Methods: </strong>Two experimental models comprising formaldehyde- and complete Freund's adjuvant (CFA)-induced arthritis evaluated the efficacy of FAR in treating arthritis. Various parameters were assessed. Then, a network pharmacology approach was applied to gain further insight into the potential mechanism and signaling pathways.</p><p><strong>Key findings: </strong>FAR significantly reduced paw volume and the arthritic score and improved the hematological and biochemical changes. Radiographic and histological examination showed the anti-arthritic efficacy of FAR, which was associated with down-regulation of pro-inflammatory mediators and upregulation of anti-inflammatory mediators. Network pharmacology analysis revealed that FAR may exert its anti-arthritic effects by targeting specific genes associated with arthritis. Pathway analysis revealed the involvement of three key signaling pathways (IL-17 signaling, TNF signaling, and toll-like receptor signaling) in the development and progression of arthritis.</p><p><strong>Conclusions: </strong>The results pointed out the protective attributes of farnesol against formaldehyde and CFA-induced arthritis via modulation of multiple targets. This study provides a valuable reference for the development of a new treatment or complementary therapy for arthritis.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"127-141"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sylvia E Shaker, Dalia B Fayed, Heba Shawky, Ebtehal K Farrag
{"title":"Co-administration of Ceratonia siliqua extract nanoparticles promotes the oral bioavailability and neurotherapeutic efficacy of donepezil in a dementia model.","authors":"Sylvia E Shaker, Dalia B Fayed, Heba Shawky, Ebtehal K Farrag","doi":"10.1093/jpp/rgae094","DOIUrl":"10.1093/jpp/rgae094","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to assess the herb-drug interactions between crude/silver nanoparticle (SNP)-loaded carob extract (Car, NCar, respectively) and donepezil-HCl (DPZ) and their impact on neurotherapeutic outcomes in a dementia model.</p><p><strong>Methods: </strong>Carob pods were subjected to ethanol extraction, and their phytoconstituents were chromatographically analysed. SNP-loaded extract was synthesized and characterized, and dementia-like symptoms were induced in Wistar rats by repeated dosing with 175 mg/kg AlCl3 for 60 days, after which the animals were treated with Car, NCar, DPZ, and combinations of Car/NCar-DPZ for 30 days. The effect of carob formulations on DPZ bioavailability was in-silico profiled and the herb-drug interactions were mathematically assessed as combination indices.</p><p><strong>Results: </strong>Different formulations significantly improved cognitive/spatial memory functions, restored dysregulated brain redox and cholinergic functions, and markedly inhibited cholinesterase, as reflected by the reduction/absence of amyloid plaques and neurofibrillary tangles. In silico profiling of the major phytoconstituents revealed their non-P-glycoprotein substrate nature and CYP3A4, 2C19, and 2C9 inhibition, which might have improved the oral bioavailability of DPZ. The combination index calculations revealed strong synergy between DPZ and both carob formulations, with the strongest effect exhibited by the DPZ/NCar combination.</p><p><strong>Conclusion: </strong>The co-administration of carob extract/SNPs represents a promising approach for enhancing the neurotherapeutic efficacy of DPZ.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"153-169"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Felipe F da Silva, Francisco das Chagas Costa, Venância A N Azevedo, Ernando I T de Assis, Geovany A Gomes, Valdevane R Araújo, Selene M de Morais, Tigressa H S Rodrigues, José R V Silva
{"title":"Croton grewioides essential oil and anethole reduce oxidative stress and improve growth of bovine primordial follicles during culture of ovarian tissue.","authors":"Felipe F da Silva, Francisco das Chagas Costa, Venância A N Azevedo, Ernando I T de Assis, Geovany A Gomes, Valdevane R Araújo, Selene M de Morais, Tigressa H S Rodrigues, José R V Silva","doi":"10.1093/jpp/rgae093","DOIUrl":"10.1093/jpp/rgae093","url":null,"abstract":"<p><strong>Objectives: </strong>This study aims to evaluate the effects of Croton grewioides essential oil (CGEO) and anethole on follicle survival, growth, and oxidative stress in cultured bovine ovarian tissues.</p><p><strong>Methods: </strong>Ovarian tissues were cultured for 6 days in a medium supplemented with different concentrations (1, 10, 100, or 1000 µg mL-1) of CGEO or anethole and then, follicular survival and growth, collagen content, and stromal cell density in ovarian tissues cultured in vitro were evaluated by histology. The mRNA levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase 1 (GPX1), peroxirredoxin 6 (PRDX6), and nuclear factor erythroid 2-related factor 2 (NRF2) were evaluated by real-time PCR. The activity of SOD, CAT, glutathione peroxidase (GPx), and thiol concentrations were investigated.</p><p><strong>Key findings: </strong>Ovarian tissues cultured with 1 µg mL-1 CGEO or anethole had a higher percentage of healthy follicles than those cultured in a control medium (P < .05). The 1 µg mL-1 CGEO also increased the number of stromal cells, collagen fibers, and thiol levels. Anethole (1 µg mL-1) increased CAT activity and reduced that of GPx. The activity of SOD was reduced by CGEO. In contrast, 1 µg mL-1 anethole reduced mRNA for CAT, PRDX1, and NRF2 (P < .05). In addition, 1 µg mL-1 CGEO reduced mRNA for CAT, PRDX6, and GPx1 (P < .05).</p><p><strong>Conclusions: </strong>The presence of 1 µg mL-1 anethole or CGEO in a culture medium promotes follicle survival and regulates oxidative stress and the expression of mRNA and activity of antioxidant enzymes in cultured bovine ovarian tissues.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1609-1619"},"PeriodicalIF":2.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Production of mRNA lipid nanoparticles using advanced crossflow micromixing.","authors":"Muattaz Hussain, Burcu Binici, Liam O'Connor, Yvonne Perrie","doi":"10.1093/jpp/rgae122","DOIUrl":"10.1093/jpp/rgae122","url":null,"abstract":"<p><strong>Objectives: </strong>Lipid nanoparticles (LNPs) play a crucial role in RNA-based therapies, and their production is generally based on nanoprecipitation and coalescence of lipids around an RNA core. This study investigated crossflow micromixing to prepare LNPs across various mixing ratios and production speeds.</p><p><strong>Methods: </strong>A range of LNPs were prepared using crossflow micromixing across production speeds of 10-500 ml/min, and their physico-chemical characteristics (size, polydispersity index (PDI), zeta potential, and mRNA encapsulation), in vitro mRNA expression and in vitro efficacy (protein expression and antibody and cytokine responses).</p><p><strong>Key findings: </strong>Our results demonstrate the reproducible production of mRNA-LNPs with controlled critical quality attributes, including high mRNA encapsulation from the initial screening scale through to GMP-scale production, where the same mixing ratio can be adopted across all product speeds from 30 to 500 ml/min used.</p><p><strong>Conclusions: </strong>We confirm the applicability of stainless-steel crossflow membrane micromixing for the entire spectrum of mRNA-LNP production, ranging from initial discovery volumes to GMP-production scale.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1572-1583"},"PeriodicalIF":2.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}