Simvastatin-Loaded Polymeric Nanoparticles: Targeting Inflammatory Macrophages for Local Adipose Tissue Browning in Obesity TreatmentClick to copy article linkArticle link copied!
- Neda MohagheghNeda MohagheghTerasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United StatesMore by Neda Mohaghegh
- Amir AhariAmir AhariTerasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United StatesDepartment of Surgery, University of California-Los Angeles, Los Angeles, California 90095, United StatesMore by Amir Ahari
- Claire ButtlesClaire ButtlesTerasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United StatesDepartment of Biology, Indiana University Bloomington, Bloomington, Indiana 47405, United StatesMore by Claire Buttles
- Saya DavaniSaya DavaniTerasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United StatesDepartment of Neurobiology, Physiology, and Behavior, University of California Davis, Briggs Hall, Davis, California 95616, United StatesMore by Saya Davani
- Hanna HoangHanna HoangTerasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United StatesDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90024, United StatesMore by Hanna Hoang
- Qiang HuangQiang HuangTerasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United StatesMore by Qiang Huang
- Yixuan HuangYixuan HuangTerasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United StatesMore by Yixuan Huang
- Bahareh HosseinpourBahareh HosseinpourTerasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United StatesDepartment of Chemistry, Carleton University, Ottawa, Ontario K1S 5B6, CanadaMore by Bahareh Hosseinpour
- Reza AbbasgholizadehReza AbbasgholizadehTerasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United StatesMore by Reza Abbasgholizadeh
- Andrea L. CottinghamAndrea L. CottinghamDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201, United StatesMore by Andrea L. Cottingham
- Neda FarhadiNeda FarhadiTerasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United StatesMore by Neda Farhadi
- Mohsen AkbariMohsen AkbariDepartment of Mechanical Engineering, University of Victoria, Victoria, British Columbia V8P 5C2, CanadaBiotechnology Center, Silesian University of Technology, Gliwice 44-100, PolandMore by Mohsen Akbari
- Heemin KangHeemin KangDepartment of Materials Science and Engineering, Korea University, Seoul 02841, Republic of KoreaMore by Heemin Kang
- Ali KhademhosseiniAli KhademhosseiniTerasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United StatesMore by Ali Khademhosseini
- Vadim JucaudVadim JucaudTerasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United StatesMore by Vadim Jucaud
- Ryan M. PearsonRyan M. PearsonDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201, United StatesMore by Ryan M. Pearson
- Alireza Hassani Najafabadi*Alireza Hassani Najafabadi*E-mail: [email protected]Terasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United StatesMore by Alireza Hassani Najafabadi
Abstract
Obesity is defined as chronic, low-grade inflammation within specific tissues. Given the escalating prevalence of obesity among individuals of all ages, obesity has reached epidemic proportions, posing an important public health challenge. Despite significant advancements in treating obesity, conventional approaches remain largely ineffective or involve severe side effects, thus underscoring the pressing need to explore and develop treatment approaches. Targeted and local immunomodulation using nanoparticles (NPs) can influence fat production and utilization processes. Statins, known for their anti-inflammatory properties, show the potential for mitigating obesity-related inflammation. A localized delivery option offers several advantages over oral and parenteral delivery methods. Here, we developed simvastatin (Sim) encapsulated within PLGA NPs (Sim-NP) for localized delivery of Sim to adipose tissues (ATs) for immunomodulation to treat obesity. In vitro experiments revealed the strong anti-inflammatory effects of Sim-NPs, which resulted in enhanced modulation of macrophage (MΦ) polarization and induction of AT browning. We then extended our investigation to an in vivo mouse model of high-fat-diet (HFD)-induced obesity. Sim-NP administration led to the controlled release of Sim within AT, directly impacting MΦ activity and inducing AT browning while inducing weight loss. Our findings demonstrated that Sim-NP administration effectively inhibited the progression of obesity-related inflammation, controlled white fat production, and enhanced AT modulation. These results highlight the potential of Sim-NP as a potent nanotherapy for treating obesity by modulating the immune system.
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