Hyaluronic Acid Nanoparticles as a Topical Agent for Treating Psoriasis.

Although conventional topical approaches for treating psoriasis have been offered as an alternative, there are still unmet medical needs such as low skin-penetrating efficacy and off-target adverse effects. A hyaluronic acid nanoparticle (HA-NP) formed by self-assembly of HA-hydrophobic moiety conjugates has been broadly studied as a nanocarrier for long-term and target-specific delivery of drugs, owing to their excellent physicochemical and biological characteristics. Here, we identify HA-NPs as topical therapeutics for treating psoriasis using in vivo skin penetration studies and psoriasis animal models. Transcutaneously administered HA-NPs were found to be accumulated and associated with pro-inflammatory macrophages in the inflamed dermis of a psoriasis mouse model. Importantly, HA-NP exerted potent therapeutic efficacy against psoriasis-like skin dermatitis in a size-dependent manner by suppressing innate immune responses and restoring skin barrier function without overt toxicity signs. The therapeutic efficacy of HA-NPs on psoriasis-like skin dermatitis was due to the outermost hydrophilic HA shell layer of HA-NPs, independent of the molecular weight of HA and hydrophobic moiety, and comparable with that of other conventional psoriasis therapeutics widely used in the clinical settings. Overall, HA-NPs have the potential as a topical nanomedicine for treating psoriasis effectively and safely.

Self-assembled hyaluronic acid nanoparticle suppresses fat accumulation via CD44 in diet-induced obese mice.

Obesity, a major risk factor for type 2 diabetes and cardiovascular diseases, is characterized by an abnormal expansion of adipose tissue. Herein, we investigated the potential of hyaluronic acid nanoparticles (HA-NPs) as therapeutics to treat obesity-related diseases by assessing the in vitro and in vivo effects of HA-NPs on adipogenesis and lipogenesis. Treatment of 3T3-L1 preadipocytes with HA-NPs resulted in a dose-dependent suppression of adipogenesis and lipid accumulation, and decreased the expression of key adipogenic and lipogenic regulators. However, these HA-NPs mediated effects were not observed in 3T3-L1 cells transfected with siRNAs against CD44, a major HA receptor. Further, HA-NP treatment of diet-induced obese (DIO) mice reduced the epididymal fat mass and suppressed the induction of adipogenic and lipogenic regulators, while these effects were attenuated in the CD44-null mice. Thus, our study provides a better understanding of how HA-NP modulates fat accumulation and presents a potential anti-obesity strategy targeting CD44.