Combined Hyaluronic Acid Nanobioconjugates Impair CD44-Signaling for Effective Treatment Against Obesity: A Review of Comparison with Other Actors

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

CD44, a key hyaluronic acid (HA) receptor, has emerged as a central mediator of adipose tissue inflammation, remodeling, and insulin resistance in obesity. Its overexpression in obese adipose depots promotes leukocyte infiltration, pro-inflammatory signaling, and extracellular matrix dysregulation processes that underlie metabolic dysfunction. This review explores the therapeutic relevance of targeting the HA-CD44 axis by synthesizing data primarily from preclinical studies, with emerging evidence from early clinical investigations. A narrative review methodology was employed to assess and compare therapeutic modalities, highlighting advances in molecular targeting, drug delivery systems, and metabolic interventions. We focus on two primary therapeutic classes: small molecules and nanobioconjugates. Small molecules, such as curcumin, metformin, and CD44 antagonists, offer systemic modulation and accessibility but are limited by their low tissue specificity and potential side effects. In contrast, HA-functionalized nanobioconjugates, including liposomes, PLGA nanoparticles, dendrimers, and exosomes, enable targeted delivery to adipose tissue, prolonged drug release, and reduced systemic toxicity. These nanosystems have demonstrated superior modulation of CD44 signaling, adipose inflammation, and glucose homeostasis in obesity models. Emerging strategies such as monoclonal antibo

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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