Vasdev Nupur, Gupta Tanisha, Bain Anoothi, Kalyane Dnyaneshwar, Polaka Suryanarayana, Tekade Rakesh Kumar
National Institute of Pharmaceutical Education and Research (NIPER) Ahmedabad, an Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Palaj, Opp. Air Force Station, Gandhinagar, 382355, Gujarat, India.
Department of Pathology, Louisiana State University Health Shreveport, Shreveport, Louisiana, USA.
AAPS PharmSciTech. 2025 Mar 27;26(4):98. doi: 10.1208/s12249-025-03085-9.
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.
肥胖是一种因久坐不动的生活方式导致的重大健康问题，并且与许多其他严重疾病相关，包括癌症、糖尿病和心血管疾病。因此，白藜芦醇（RES）因其类似运动的效果而作为一种新兴治疗剂受到关注。然而，RES的不稳定性和低水溶性限制了其应用。本研究报告聚焦于使用负载树枝状聚合物复合物的脂质体制剂对白藜芦醇进行负载、增溶和持续递送。通过进行各种试验研究了该制剂的安全性和有效性。采用质量源于设计（QbD）方法对负载DEN-RES复合物的脂质体进行了优化，发现其粒径、多分散指数（PDI）和zeta电位分别为159.29±0.58nm、0.206±0.008和-7.2±0.14mV，遵循一级释放动力学以实现白藜芦醇的持续释放。发现SIRT1和AMPK基因的mRNA水平上调了两倍多，而LIPO-DEN-RES下调了脂肪细胞中PPARγ的mRNA表达。因此，用LIPO-DEN-RES处理后在3T3-L1细胞中检测到的mRNA水平的调节证实了该制剂在解决肥胖问题方面的潜力。
