Chlorella‐Based “Carrier‐as‐Therapeutic” Platform: Dual‐Pathology Therapy and Translational Efficacy for Meibomian Gland Dysfunction

Abstract Meibomian gland dysfunction (MGD), a leading cause of evaporative dry eye, is poorly managed by conventional therapies due to short‐lived efficacy, frequent dosing, and adverse effects. Here, Chlo.@Dex—a “carrier‐as‐therapeutic” system combining Chlorella (Chlo.) and dexamethasone (Dex)— is developed to address MGD's dual pathogenesis (lipid deficiency + inflammation) via Chlo.’s inherent “tripartite functions” (sustained drug release, lipid supplementation, intrinsic bioactivity). Fabricated via adsorption‐freeze‐drying, Chlo.@Dex retains a porous structure for sustained Dex release while preserving Chlo.’s meibum‐mimetic lipids and bioactive components. In vitro, it enhanced the viability and differentiation of human meibomian gland epithelial cells, reduced pro‐inflammatory cytokines (e.g., IL‐1β by 64.6%) and reactive oxygen species (35.6%), and showed no cytotoxicity. In a rabbit MGD model, once‐daily Chlo.@Dex outperformed single‐agent treatments (Dex/Chlo. alone): it improved eyelid margin morphology, repaired glandular structure, increased tear film lipid layer thickness, and suppressed inflammation. Critically, Chlo.@Dex cleared via the nasolacrimal duct without systemic accumulation, confirming safety. Chlo.@Dex leverages Chlo.’s tripartite functions to achieve “immediate lipid replenishment (alleviating symptoms)” and “long‐term gland repair (reversing pathology)”—offering a promising MGD therapy with reduced dosing frequency. This work also advances natural microalgae as a multifunctional ophthalmic platform, overcoming the limitations of traditional “passive drug containers”.