{"title":"Harnessing Exercise-Like Benefits of Protonation prone Liposomal Resveratrol in Differentiated Fat Cells: A Proof-of-Concept Study","authors":"Nupur Vasdev, Tanisha Gupta, Anoothi Bain, Dnyaneshwar Kalyane, Suryanarayana Polaka, Rakesh Kumar Tekade","doi":"10.1208/s12249-025-03085-9","DOIUrl":null,"url":null,"abstract":"<div><p>Obesity is a significant health issue resulting from a sedentary lifestyle and is linked to numerous other serious conditions, including cancer, diabetes, and cardiovascular diseases. Consequently, resveratrol (RES) is gaining attention as an emerging therapeutic agent due to its exercise-like effects. However, RES's instability and low aqueous solubility have limited its applications. This research report focuses on the loading, solubilization, and sustained delivery of RES using a dendrimer complex loaded liposomal formulation. The safety and efficacy of formulation was studied by performing various assays. The DEN-RES complex loaded liposomes were optimized using a Quality by Design (QbD) approach whereas particle size, PDI and zeta potential were found to be 159.29 ± 0.58 nm, 0.206 ± 0.008, and -7.2 ± 0.14 mV, which followed first-order release kinetics for sustained RES release. The mRNA levels of the SIRT1 and AMPK genes were found to be upregulated by more than two folds, whereas the LIPO-DEN-RES downregulated the mRNA expression of PPARγ in adipocytes. Therefore, the modulation of mRNA levels detected in 3T3-L1 cells post-treatment with the LIPO-DEN-RES validates the formulation's potential in addressing obesity.</p><h3>Graphical Abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 4","pages":""},"PeriodicalIF":4.0000,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"AAPS PharmSciTech","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1208/s12249-025-03085-9","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Obesity is a significant health issue resulting from a sedentary lifestyle and is linked to numerous other serious conditions, including cancer, diabetes, and cardiovascular diseases. Consequently, resveratrol (RES) is gaining attention as an emerging therapeutic agent due to its exercise-like effects. However, RES's instability and low aqueous solubility have limited its applications. This research report focuses on the loading, solubilization, and sustained delivery of RES using a dendrimer complex loaded liposomal formulation. The safety and efficacy of formulation was studied by performing various assays. The DEN-RES complex loaded liposomes were optimized using a Quality by Design (QbD) approach whereas particle size, PDI and zeta potential were found to be 159.29 ± 0.58 nm, 0.206 ± 0.008, and -7.2 ± 0.14 mV, which followed first-order release kinetics for sustained RES release. The mRNA levels of the SIRT1 and AMPK genes were found to be upregulated by more than two folds, whereas the LIPO-DEN-RES downregulated the mRNA expression of PPARγ in adipocytes. Therefore, the modulation of mRNA levels detected in 3T3-L1 cells post-treatment with the LIPO-DEN-RES validates the formulation's potential in addressing obesity.
肥胖是由久坐不动的生活方式导致的重大健康问题，与许多其他严重疾病有关，包括癌症、糖尿病和心血管疾病。因此，白藜芦醇（RES）作为一种新兴的治疗药物因其类似运动的作用而受到关注。然而，RES的不稳定性和较低的水溶性限制了它的应用。本研究报告的重点是负载，增溶和持续递送的RES使用树突复合物负载脂质体制剂。通过各项试验研究了该制剂的安全性和有效性。采用质量设计（Quality by Design, QbD）方法对载药的denn -RES复合物脂质体进行了优化，其粒径、PDI和zeta电位分别为159.29±0.58 nm、0.206±0.008和-7.2±0.14 mV，符合RES持续释放的一级释放动力学。SIRT1和AMPK基因的mRNA水平上调了两倍以上，而lipoo - den - res下调了脂肪细胞中PPARγ的mRNA表达。因此，用lipoo - den - res处理3T3-L1细胞后检测到的mRNA水平的调节验证了该配方在解决肥胖问题方面的潜力。图形抽象
期刊介绍：
AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.
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