Pharmaceutical Research最新文献_第3页

Modification of Peptide and Permeation Enhancer In Vitro Release Rates by Dispersion with a Gel-Forming Polymer. 凝胶形成聚合物分散修饰肽和渗透增强剂的体外释放率。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-06-06 DOI: 10.1007/s11095-025-03870-y

Pradnya Bapat, Sheena Lee Luy, Neha Panchabhai, Lynne S Taylor

{"title":"Modification of Peptide and Permeation Enhancer In Vitro Release Rates by Dispersion with a Gel-Forming Polymer.","authors":"Pradnya Bapat, Sheena Lee Luy, Neha Panchabhai, Lynne S Taylor","doi":"10.1007/s11095-025-03870-y","DOIUrl":"10.1007/s11095-025-03870-y","url":null,"abstract":"Purpose: Herein, we evaluated the release properties of peptides when combined with a permeation enhancer (PE) as well as a gel-forming polymer.Methods: Octreotide was selected as a model hydrophilic peptide, while cyclosporine was chosen as a lipophilic peptide. The PEs studied were sodium decanoate (SD) and salcaprozate sodium (SNAC). To achieve synchronous release of the peptide and the PE, copovidone, a gel-forming polymer, was also included. Solid dispersions containing peptide, PE and polymer were prepared by dissolving all components in methanol followed by solvent removal. Dispersions were evaluated using powder X-ray diffraction. Surface normalized release rates of peptide, SNAC and copovidone alone and in combination were measured using Wood's intrinsic dissolution rate apparatus.Results: Octreotide dissolved rapidly while amorphous cyclosporine release rate was essentially undetectable. The PEs and neat polymer also dissolved rapidly. However, the intrinsic dissolution rates of octreotide and SNAC differed by a factor of two. Addition of copovidone to the formulation led to synchronous release of octreotide and SNAC, controlling their release. Furthermore, both SNAC and SD enhanced the dissolution rate of the polymer, leading to very rapid release of the components from the ternary dispersion. Cyclosporine released well from dispersions when present at a very low concentration, with a deterioration in release performance being observed at higher drug loadings.Conclusions: Based on the findings of this study, inclusion of a gel-forming polymer may help synchronize the release of a hydrophilic peptide and a PE, which in turn may improve co-localization at the epithelial membrane.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1003-1020"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249155","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}

引用次数: 0

Controlling Gastric Delivery of a GIP/GLP1 Peptide in Monkeys by Mucoadhesive SNAC Tablets. 黏附SNAC片控制猴子胃中GIP/GLP1肽的传递。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-06-13 DOI: 10.1007/s11095-025-03881-9

Huyen Tran, Jennifer Martin, Mridula Dogra, Jenna Walker, Donald Risley, Aktham Aburub

{"title":"Controlling Gastric Delivery of a GIP/GLP1 Peptide in Monkeys by Mucoadhesive SNAC Tablets.","authors":"Huyen Tran, Jennifer Martin, Mridula Dogra, Jenna Walker, Donald Risley, Aktham Aburub","doi":"10.1007/s11095-025-03881-9","DOIUrl":"10.1007/s11095-025-03881-9","url":null,"abstract":"Objective: Gastric delivery has been utilized for oral delivery of peptides. However, target site of the delivery is uncontrollable due to the housekeeping wave. In addition, dilution and spreading of peptides and permeation enhancers in the stomach may limit the oral peptide bioavailability. In this study, we developed mucoadhesive tablets containing SNAC and a GIP/GLP1 dual agonist peptide (LY) to localize the peptide delivery and minimize the dilution effect in the stomach.Methods: The mucoadhesive tablets were prepared as bilayer or trilayer tablets with sodium alginate on one or both sides of the formulation layer (LY/SNAC). Mucoadhesion tests were conducted using a rotating cylinder mounted with isolated rat and minipig gastric tissues, and in vivo in monkeys. Oral bioavailability of the peptide was determined in monkeys via oral administration of the mucoadhesive tablets.Results: The mucoadhesive tablets dissolved > 80% within 15 min at pH 6.8. The trilayer SNAC tablets adhered to the isolated gastric tissues. Following oral administration to monkeys, 10/10 mucoadhesive tablets were retained in the monkey stomach 10-20 min post-dose compared to 1/3 SNAC control tablets. Oral bioavailability of LY peptide was of similar magnitude as that achieved with the SNAC control tablet. In vivo dissolution of the mucoadhesive tablets was slower than the control tablets leading to lower SNAC concentration at the tablet site in the monkey stomach.Conclusion: These data suggest that the mucoadhesive tablets improved gastric retention but did not increase oral bioavailability of the LY peptide following gastric delivery in monkeys.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1021-1033"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sialic Acid-based Glycoconjugation on Myricetin-encapsulated Cationic Nanocarriers for the Treatment of Alzheimer's. 杨梅素包封的阳离子纳米载体唾液酸糖缀合治疗阿尔茨海默病。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-06-09 DOI: 10.1007/s11095-025-03877-5

Tripti Halder, Niyati Acharya

{"title":"Sialic Acid-based Glycoconjugation on Myricetin-encapsulated Cationic Nanocarriers for the Treatment of Alzheimer's.","authors":"Tripti Halder, Niyati Acharya","doi":"10.1007/s11095-025-03877-5","DOIUrl":"10.1007/s11095-025-03877-5","url":null,"abstract":"Purpose: The current study was conducted to develop and evaluate sialic acid grafted cationic myricetin (MY) fabricated nanostructured lipid carrier (Sia-Cat-MY-NLC) for Alzheimer's disease (AD) management.Methods: In-vitro amyloid beta aggregation inhibition and mitochondrial membrane potential of prepared NLCs were observed in SH-SY5Y cells. The transendothelial electrical resistance was measured through hCMEC/D3 cells. Pharmacokinetic and pharmacodynamic studies were conducted to evaluate neuropharmacokinetic parameters and levels of AD hallmarks in AD rats.Results: The optimized formulations showed particle sizes (142.26 ± 24.16 nm and 236.3 ± 15.26 nm), zeta potentials (36.5 ± 2.43 mv and -2.4 ± 1.30 mv) respectively for Cat-MY-NLC and Sia-Cat-MY-NLC. Prepared NLCs treatments revealed significant neuroprotective effects in SH-SY5Y cells followed by the ability to cross the in-vitro BBB model. Results of pharmacokinetic studies showed 5.3 and 5.88 folds enhanced bioavailability with Cat-MY-NLC and Sia-Cat-MY-NLC administration respectively.Conclusions: The results of enzymatic analysis showed a significant (p < 0.05) restoration of AD hallmark levels in the brain after Sia-Cat-MY-NLC treatment than Cat-MY-NLC.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"947-959"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Finite Absorption Time Concept Guiding Model Informed Drug & Generics Development in Clinical Pharmacology. 有限吸收时间概念指导模型指导临床药理学药物和仿制药开发。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-06-05 DOI: 10.1007/s11095-025-03878-4

Panos Macheras, Athanasios A Tsekouras, Sergio Sánchez-Herrero, Kosmas Kosmidis

引用次数: 0

Impact of Initial Aggregate Level on Aggregation Potential of Monoclonal Antibodies in Different Buffer Systems. 不同缓冲体系中初始聚集水平对单克隆抗体聚集电位的影响。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-06-06 DOI: 10.1007/s11095-025-03874-8

Anuj Shrivastava, Anurag S Rathore

{"title":"Impact of Initial Aggregate Level on Aggregation Potential of Monoclonal Antibodies in Different Buffer Systems.","authors":"Anuj Shrivastava, Anurag S Rathore","doi":"10.1007/s11095-025-03874-8","DOIUrl":"10.1007/s11095-025-03874-8","url":null,"abstract":"Purpose: This study investigates the stability and kinetics of degradation when monoclonal antibodies (mAbs) process intermediates are stored in commonly used Protein A elution buffers, including citrate, acetate, and glycine, at varying pre-existing aggregates levels (low: 1-5%, moderate: 5-15% and high: 15-25%) at 4°C and 30°C to simulate standard and worst-case conditions.Methodology: mAb samples were subjected to thermal stress to achieve different levels of initial aggregates. The pre-aggregated samples were then incubated in different buffers at 4°C and 30°C to assess aggregation rates and stability. Aggregates were quantified using dynamic light scattering (DLS) integrated with machine learning (ML).Result: At 30°C, half-life reductions for citrate, acetate, and glycine buffers were 6.30-fold, 6.48-fold, and 9.64-fold, respectively, compared to 4°C, with glycine buffer offering the best stability, while citrate buffer provides the least. At higher initial aggregate levels, half-lives decreased by 2.15-, 1.95-, and 1.73-fold for citrate, acetate, and glycine buffers, respectively, compared to lower initial aggregates. Second-order kinetics dominated in samples having lower initial aggregate levels, while first-order kinetics prevailed in medium and high initial aggregate levels. Glycine buffer at 4°C with low initial aggregates achieved the highest half-life of 129 days, whereas citrate buffer at 30°C with high initial aggregate exhibited the lowest stability, with a half-life of 3.5 days.Conclusion: The findings highlight the significance of using an optimal buffer system and appropriate storage conditions for in-process intermediates during mAb manufacturing to have a robust process that delivers safe and efficacious biotherapeutic products.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"973-986"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Preclinical Toxicity Study and Tissue Distribution of YSCH- 01 Injection via Intratumoral Injection, Intravenous Injection, and Intraperitoneal Injection in Syrian Hamsters. YSCH- 01注射液瘤内、静脉、腹腔注射对叙利亚仓鼠的临床前毒性研究及组织分布。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-05-08 DOI: 10.1007/s11095-025-03863-x

Ruoyu Chen, Xian-Long Fang, Hafiz Khuram Raza

{"title":"Preclinical Toxicity Study and Tissue Distribution of YSCH- 01 Injection via Intratumoral Injection, Intravenous Injection, and Intraperitoneal Injection in Syrian Hamsters.","authors":"Ruoyu Chen, Xian-Long Fang, Hafiz Khuram Raza","doi":"10.1007/s11095-025-03863-x","DOIUrl":"10.1007/s11095-025-03863-x","url":null,"abstract":"Background: Recombinant L-IFN Adenovirus (YSCH-01) is a modified oncolytic adenovirus, which showed good curative effects in a variety of solid tumors. The safety of YSCH-01 needs to be evaluated for non-clinical research.Methods: This toxicity and distribution study of YSCH-01 injection via ITU/IV/IP injection in Syrian Hamster was conducted to prepare an investigational new drug (IND) application. The endpoints included mortality/moribundity, clinical observation, body weight, palpable mass examination, food consumption, ophthalmology, and clinical pathology. Toxicokinetics, ADA test, viral shedding, and tissue bio-distribution were analyzed.Results: The severely toxic dose in 10% of animals was 1 × 1011 VP/animal, > 2 × 1011 VP/kg, and 6.7 × 1011 VP/kg for ITU groups, IV groups and IP groups, respectively. The antibody titers of recombinant L-IFN adenovirus were significantly increased following YSCH-01 administration, and slightly lower during recovery period. YSCH-01 gDNA can be shed through the administration site, saliva and feces, and almost no urine. In the ITU, IV, and IP injection groups, YSCH-01 was distributed in the whole blood and all collected organs with Tmax in most whole blood/tissues of 2.00-4.00 days and L-IFN was detected in all tumor and serum samples, with a Tmax of 2.00-4.00 days, full or partial clearance of YSCH-01 and L-IFN was noted in most tissues/organs or tumor and serum on D28.Conclusions: Our study demonstrated the toxicity and potential toxicity of YSCH-01 in Syrian hamsters and evaluated its tissue distribution in hamsters after a single administration. STD10 results in hamsters support the safety of the estimated dosage for future clinical studies.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"917-933"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hispidulin Isolated from the Leaves of Clerodendrum inerme (L.) Gaertn Suppresses Trigeminovascular System Activation in a Rat Model Mimicking Migraine. 从毛竹叶中分离得到的Hispidulin在模拟偏头痛的大鼠模型中，Gaertn抑制三叉神经血管系统的激活。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-05-09 DOI: 10.1007/s11095-025-03864-w

Pi-Chuan Fan, Ming Tatt Lee, Tzu-Hsuan Lai, Wei-Jan Huang, Lih-Chu Chiou

{"title":"Hispidulin Isolated from the Leaves of Clerodendrum inerme (L.) Gaertn Suppresses Trigeminovascular System Activation in a Rat Model Mimicking Migraine.","authors":"Pi-Chuan Fan, Ming Tatt Lee, Tzu-Hsuan Lai, Wei-Jan Huang, Lih-Chu Chiou","doi":"10.1007/s11095-025-03864-w","DOIUrl":"10.1007/s11095-025-03864-w","url":null,"abstract":"Background: Hispidulin (6-methoxy-4',5,7-trihydroxyflavone) is a flavonoid commonly found in various plant products, including the leaves of Clerodendrum inerme (L.) Gaertn (CI). While there's an abundance of literature describing the therapeutic effect of hispidulin and CI in oncological, immunological, and dermatological models, their effect on neuropsychiatric disorders is also of research interest.Objective: The previous reports on the neuroprotective and GABAA receptor positive modulatory effect of hispidulin may render it as a possible novel candidate as an antimigraine agent.Methods: In the present study, we employed the intracisternal instillation of capsaicin in anesthetized rats to induce the activation of trigeminovascular system (TGVS), which mimics the histopathological hallmarks of migraine that include increased neuronal activation in the trigeminal cervical complex (TCC), calcitonin gene-related peptide (CGRP) immunoreactivity in the trigeminal ganglia (TG) and CGRP depletion in the dura mater.Results: Administration of hispidulin (4, 10, and 50 mg/kg, i.p.) significantly reduced all three TGVS activation parameters induced by i.c. capsaicin. However, pre-treatment of a selective antagonist for α6 subunit-containing GABAA receptor, furosemide (20 mg/kg, i.p.), did not significantly reverse the antimigraine effect of hispidulin.Conclusion: To the best of our knowledge, this is the first report on hispidulin's suppressive effect on preclinical model of migraine. Further studies are required to explore the mechanism(s) of the antimigraine effect of hispidulin. However, these findings could potentially guide future clinical studies of hispidulin, with the aim of improving human health.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1035-1045"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Decrease in In Vivo Efflux Transport via P-glycoprotein at the Rat Inner Blood-Retinal Barrier by Peripheral Administration of Lipopolysaccharide. 外周给药降低p -糖蛋白在大鼠血液-视网膜内屏障的体内外排转运。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-06-03 DOI: 10.1007/s11095-025-03872-w

Kiyotaka Daikohara, Shin-Ichi Akanuma, Miyu Kawanishi, Yuma Tega, Ken-Ichi Hosoya

{"title":"Decrease in In Vivo Efflux Transport via P-glycoprotein at the Rat Inner Blood-Retinal Barrier by Peripheral Administration of Lipopolysaccharide.","authors":"Kiyotaka Daikohara, Shin-Ichi Akanuma, Miyu Kawanishi, Yuma Tega, Ken-Ichi Hosoya","doi":"10.1007/s11095-025-03872-w","DOIUrl":"10.1007/s11095-025-03872-w","url":null,"abstract":"Purpose: This study aimed to determine in vivo alterations in the rat retinal distribution of a substrate for P-glycoprotein (P-gp), which restricts drug transport to the retina at the inner blood-retinal barrier (BRB), by peripheral administration of lipopolysaccharide (LPS), an inflammatory agent.Methods: Using retinal capillaries isolated from rats 24 h after peripheral 5 mg/kg LPS administration, transport analyses with a fluorescent substrate of P-gp were performed. In vivo retinal distribution of [3H]digoxin, a P-gp substrate, in the LPS-administered rats was evaluated after intravenous or intracarotid artery injection. The mRNA and protein expression levels of P-gp in the retinal capillaries were evaluated.Results: P-gp-mediated luminal transport of the fluorescent substrate was significantly attenuated in retinal capillaries of the LPS-administered rats. Moreover, in vivo retinal [3H]digoxin distribution in LPS-injected rats was significantly greater than that in saline-injected rats. Since the retinal distribution of [3H]D-mannitol, a paracellular transport marker, was not significantly altered in LPS-treated rats, it is suggested that in vivo elevation of retinal [3H]digoxin distribution is caused by P-gp downregulation at the inner BRB, but not a change in paracellular transport in the barrier. In retinal capillaries isolated from LPS-administered rats, expression analyses of P-gp mRNAs and protein indicated a reduction in its expression on the luminal membrane of the inner BRB.Conclusion: Our study demonstrated that in vivo retinal distribution of P-gp substrates was elevated in LPS-administered rats via a decrease in the function and expression of P-gp at the inner BRB.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"907-915"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Liposomal Vardenafil and Linagliptin Combined with Irinotecan for Synergistic Colorectal Cancer Therapy. 伐地那非、利格列汀联合伊立替康脂质体协同治疗结直肠癌。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-06-05 DOI: 10.1007/s11095-025-03876-6

Xian Zhao, Ruijie Xu, Yuanyuan Zhai, Yi Wang, Yuxin Zhang, Yuan Tian, Fengguo Xu, Pei Zhang

{"title":"Liposomal Vardenafil and Linagliptin Combined with Irinotecan for Synergistic Colorectal Cancer Therapy.","authors":"Xian Zhao, Ruijie Xu, Yuanyuan Zhai, Yi Wang, Yuxin Zhang, Yuan Tian, Fengguo Xu, Pei Zhang","doi":"10.1007/s11095-025-03876-6","DOIUrl":"10.1007/s11095-025-03876-6","url":null,"abstract":"Background: Irinotecan (CPT-11) is a standard first-line chemotherapy treatment for colorectal cancer (CRC). However, its clinical application is often comprised by gastrointestinal toxicity and limited therapeutic efficacy. Our previous study has revealed that the combination of Vardenafil (Vard) and Linagliptin (Linag) significantly alleviated CPT-11-induced intestinal toxicity in both in vitro and in vivo models. It remains unclear whether this combination can synergistically enhance the anticancer activity of CPT-11.Methods: The in vitro synergism of Vard, Linag, and CPT-11 was assessed using cell viability assays on CRC cell lines, including HCT116, SW620, and HT29. An in vivo xenograft mouse model was established to evaluate the drug efficacy of both the original and liposomal forms of Vard and Linag combined with CPT-11. Additionally, untargeted metabolomics was utilized to explore the potential mechanisms underlying the observed synergistic effects.Results: In vitro, the combination of Vard and Linag synergistically enhanced the anticancer activity of CPT-11 in CRC cell lines. In vivo, liposomal formulations of Vard and Linag tended to accumulate at the tumor site, improving drug targeting and synergistically enhancing the anticancer efficacy of CPT-11. Untargeted metabolomics analysis revealed that this synergistic effect was probably mediated through the regulation of lysophospholipid metabolism.Conclusion: Liposomal Vard and Linag combined with CPT-11 demonstrated a synergistic anti-CRC effect, offering valuable insights into novel combination therapies in CRC treatment.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"935-945"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advancing Pharmaceutical Security: Noninvasive Detection of Falsified Vaccines and Drugs Using wNMR. 推进药物安全：使用wNMR无创检测伪造疫苗和药物。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-06-13 DOI: 10.1007/s11095-025-03880-w

Marc B Taraban, Katharine T Briggs, Pratima Karki, Leonid Grunin, Y Bruce Yu

{"title":"Advancing Pharmaceutical Security: Noninvasive Detection of Falsified Vaccines and Drugs Using wNMR.","authors":"Marc B Taraban, Katharine T Briggs, Pratima Karki, Leonid Grunin, Y Bruce Yu","doi":"10.1007/s11095-025-03880-w","DOIUrl":"10.1007/s11095-025-03880-w","url":null,"abstract":"Objective: To develop and apply noninvasive analytical technologies to detect falsified vaccines and drugs.Methods: Univariate and multivariate methods, based on the water nuclear magnetic resonance (wNMR) technology, was explored as a tool for noninvasive detection of simple and sophisticated falsified vaccines, biotherapeutics and anesthetics. All wNMR measurements were done noninvasively on sealed vials, prefilled syringes, and injection pens. Saline USP served as a simple falsified drug product while highly similar vaccines and drugs (brand vs. generics/biosimilars) served as each other's sophisticated falsified drug products for technology development and testing.Results: Simple falsified drug products, represented by USP saline, can be differentiated from authentic vaccines and drugs by univariate wNMR. Sophisticated falsified drug products, represented by highly similar products, can be differentiated from authentic ones by univariate wNMR in some cases and by multivariate wNMR in all cases, attesting to the high discriminating power of wNMR in product authentication. The multivariate methods generate 2D and 3D data arrays that may serve as fingerprints of vaccines and drugs.Conclusions: A suite of noninvasive analytical methods, based on the wNMR technology, have been developed to detect falsified vaccines and drugs. wNMR analyzes vaccines and drugs in their primary containers without opening and uses benchtop instruments with no wet lab operations and no reagents. wNMR detection of falsified drug products may be implemented in low-resource settings for enhanced pharmaceutical security and preventive pharmacovigilance.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"987-1001"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0