Abstract
Psoriasis is an inflammatory skin disease influenced by the immune system, with a notable tendency to recurrence, characterized by irregular keratinocyte multiplication, presence of inflammatory cells, excessive secretion of pro-inflammatory chemicals, and abnormal blood vessel proliferation. Even though the detailed pathogenesis of psoriasis has not been fully determined, simultaneous targeting multiple pathways involved in disease progression may be more effective than currently available therapeutic strategies. In this study, we developed a bilirubin-conjugated hyaluronic acid-assembled, lapatinib/rosiglitazone-coloaded nanoparticle (LR@HBn) to target both peroxisome proliferator-activated receptor γ (PPARγ) and epidermal growth factor receptor (EGFR) as well as intervene nuclear factor kappa B (NF-κB) signaling to effectively alleviate the progression of psoriasis by suppressing inflammatory microenvironment, preventing abnormal cellular growth, scavenging reactive oxygen species (ROS), and inhibiting interleukin-17A secretion. The formulation of LR@HBn was optimized by measuring particle size, potential, drug loading capacity and ROS response ability. For the convenience of topical administration, LR@HBn was encapsulated in a volatile film-forming carboxymethyl chitosan gel (LR@HBn-G). Ex vivo skin penetration retention and in vivo therapeutic effect and recurrence prevention ability were also evaluated. The optimized LR@HBn had an average particle size (79.07 ± 1.10 nm), a negative zeta potential of (-19.37 ± 4.22 mV) and high entrapment efficiency over 80 %, achieving high penetration and long retention of the pharmacological agents at the lesion site. Owing to its capacity to participate in decomposition reactions in response to ROS, LR@HBn is able to transport pharmacological cargo specifically at the lesion site. In vitro and in vivo experiments revealed excellent antioxidative, anti-inflammatory, anti-proliferative features and safety of LR@HBn, with resultant attenuation of psoriatic disease progression and suppression of recurrence. Taken collectively, these results point to LR@HBn as a promising and advanced strategy for treating psoriasis by administering topically.