• Nanocarrier Delivery of Postbiotics: A New Frontier in Managing Inflammaging
  • Seyed Amin Mousavisadr,1 Samila Farokhimanesh,2,* Anisa Pirayadi,3 Zahra Nasiri,4
    1. Bioprocess Engineering Department, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology
    2. Institute of medical sciences and technologies, SR.C, Islamic Azad University
    3. Department of biology, SR.C,. Islamic Azad University
    4. Department of biology, SR.C,. Islamic Azad University


  • Introduction: Inflammaging is a new concept that seeks to explain the reasons behind the increasing incidence of age-related diseases. This theory interprets the close association between aging and inflammation, the cellular mechanism triggered by immune cells such as monocytes and macrophages, which secrete pro-inflammatory cytokines like tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). These molecules orchestrate the inflammatory cascade, promoting tissue repair and restoring homeostasis. Normally, inflammation is an immune response to infections or tissue damage, but numerous studies show that aging could lead to an imbalance in pro-inflammatory and anti-inflammatory cytokines, causing an increase in pro-inflammatory cytokines even without overt infection. This rise in pro-inflammatory status results in chronic, low-grade inflammation, termed inflammaging, and is a major contributing factor to several age-related dysfunctions including cardiovascular disease, type II diabetes, Alzheimer’s disease, multiple sclerosis, and cancer. Furthermore, immunosenescence, which is known as the gradual decline in immune system function with age, oxidative inflammation, and DNA damage, along with the inflammatory mediators imbalance, activate NF-𝜅B, TOR, RIG-1, Notch, Sirtuins, TGF-𝛽, and Ras signaling pathways, ultimately contributing to inflammaging. Moreover, various age-related diseases lead to an increase in pro-inflammatory cytokines, suggesting a bidirectional relationship between inflammation and aging. In recent years, countless efforts have been made to address age-related diseases; however, the complex network of cellular mechanisms involved in these disorders has limited the development of new therapeutics. conversely, inflammaging illuminates one side of this complex cellular network by explaining the association between inflammation and aging. Thus, new therapeutics could be explored to combat inflammaging and manage age-related disorders. Among all new bioactive materials, postbiotics, bioactive components derived from probiotics, have drawn significant attention because of their broad-spectrum bioactivity, such as anti-inflammatory, antioxidant, and immunomodulatory properties. Nevertheless, the low stability and bioavailability of postbiotics have limited their medical applications. Nanotechnology-based drug delivery has been studied to overcome the drawbacks of postbiotics and to enhance their targeted delivery. Thus, nanoparticles (NPs), such as lipid-based NPs, polymeric NPs, and inorganic NPs, has been applied to address the applicability of postbiotics. As a result, lipid-based NPs, including solid lipid NPs (SLNs) and liposomes, offer promising advantages for gut drug delivery due to their capacity to encapsulate both hydrophobic and hydrophilic substances as well as their high biocompatibility and biodegradability. Also, chitosan and poly lactic-co-glycolic acid (PLGA) NPs act as promising carriers for colon-targeted drug delivery to combat colon cancer and inflammatory bowel disease (IBD). Moreover, mesoporous silica nanoparticles (MSNs) serve as an effective platform for drug delivery due to their biocompatibility, structural stability, and chemical inertness. Additionally, hydrogel microfibers possess a negatively charged surface that enables targeted delivery of hydrophobic substances to inflamed tissues.
  • Methods: A systematic search was conducted in PubMed, Scopus, and Web of Science using keywords such as “inflammaging,” “postbiotics,” “inflammation,” “nanocarriers,” and “drug delivery,” along with their combinations. Articles published until 2025 that addressed the molecular mechanisms of inflammaging, bioactivities of postbiotics, and targeted nanotechnology-based delivery of postbiotics were selected. Data were extracted on postbiotic classification, therapeutic potential, and nanocarriers suitable for targeted delivery of postbiotics. Included studies were qualitatively analyzed and synthesized to provide a comprehensive overview of current advances in the management of age-related diseases and the challenges of employing postbiotics as novel therapeutics for managing inflammaging.
  • Results: This review revealed extensive evidence supporting the role of postbiotics in mitigating inflammaging through anti-inflammatory, immunomodulatory, and antioxidant properties. These bioactivities collectively make postbiotics promising pharmaceuticals for managing inflammaging. However, low stability and bioavailability of postbiotics are critical challenges that could be alleviated by nanocarrier-mediated drug delivery, which can enhance both stability and bioavailability and also provide targeted delivery.
  • Conclusion: Inflammaging, as a novel concept, reveals the correlation between aging and inflammation and its role in disease progression that affects human health. Given the diverse disorders triggered by inflammaging, designing new therapeutic agents is of utmost importance. Accordingly, postbiotics, on account of their safety and various bioactivities, are suggested by a considerable number of studies for managing inflammaging. However, challenges have limited their application, which could be addressed by nanotechnology-based drug delivery to enhance their stability, bioavailability, and targeted delivery. Certainly, additional studies are essential to determine the exact role of postbiotics and their effectiveness in managing the listed dysfunctions.
  • Keywords: Inflammaging, Postbiotics, Nanocarrier, Inflammation, Drug delivery.