Combatting psoriasis with nanomedicine: gamma-amino butyric acid-chitosan nanoparticles as a targeted anti-psoriatic therapy

Abstract The chronic inflammation and oxidative stress are the most deleterious pathogenic factors of psoriasis (PS). While gamma-aminobutyric acid (GABA) possesses well-documented immunomodulatory and antioxidant properties, its therapeutic potential is limited by bioavailability and targeting. Chitosan nanoparticles (CSNP) offer a promising drug delivery platform to overcome GABA limitations. This study aimed to augment the dermatological efficacy of GABA by encapsulation within CSNPs to overcome its skin penetration limitations, thereby creating an advanced transdermal delivery system for sustained anti-psoriatic local action. TEM revealed spherical, monodisperse GABA-CSNPs. Dynamic light scattering (DLS) confirmed a nanoscale size (57.63 nm), highly positive surface charge (+ 35.93 mV) and excellent colloidal stability. In vitro, GABA-CSNPs demonstrated superior antioxidant (using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay) and anti-inflammatory (membrane stabilization) activities compared to free GABA or blank CSNPs, beside enhanced biocompatibility (using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay). A PS-like model was induced in rats using 5% imiquimod (IMQ). Animals were divided into five groups: negative control, psoriatic control (PC) (62.5 mg of Aldara® cream) and IMQ groups treated with free GABA ( 200 mg/kg), unloaded CSNPs (100 mg/kg), or GABA-CSNPs (100 mg/kg). The GABA-CSNPs treatment group showed the most significant clinical improvement, reducing scaling and erythema. Mechanistically, therapy restored epidermal architecture, ameliorated oxidative stress by lowering malondialdehyde (MDA) and elevating superoxide dismutase (SOD) and catalase (CAT) levels, and potently suppressed key pro-inflammatory cytokines (IL-1 β , IL-6 and TNF- α ) in skin tissue. In conclusion, GABA-CSNPs constitute a novel and highly effective antipsoriatic nanotherapeutic platform. The formulation synergizes the inherent bioactivity of GABA with the enhanced delivery and targeting capabilities of CSNPs, resulting in a potent dual-action therapy that alleviates oxidative damage and modulates the dysregulated immune response central to psoriatic pathology.