Abstract

Ginger, a Zingeberaceae family member, is notable for its anti-inflammatory properties. This study explores the pharmaceutical mechanisms of ginger and red palm wax co-extract, developing novel niosomal formulations for enhanced transdermal delivery. Evaluations included physical characteristics, drug loading, in vitro release, network pharmacology, molecular docking, and biocompatibility. The niosomal ginger with red palm wax gel (NGPW) exhibited non-Newtonian fluid properties. The optimized niosome formulation (cholesterol: Tween80: Span60 = 12.5: 20: 5 w/w) showed a high yield (93.23 %), high encapsulation efficiency (54.71 %), and small size (264.33 ± 5.84 nm), prolonging in vitro anti-inflammatory activity. Human skin irritation and biocompatibility tests on 1 % NGPW showed favorable cytotoxicity and hemocompatibility results (ISO10993). Network pharmacology identified potential targets, while molecular docking highlighted high affinities between gingerol and red palm wax compounds with TRPM8 and TRPV1 proteins, suggesting pain inhibition via serotonergic synapse pathways. NGPW presents a promising transdermal pain inhibitory drug delivery strategy.