Orally fast dissolving α-lipoic acid electrospun nanofibers mitigates lipopolysaccharide induced inflammation in RAW 264.7 macrophages

α-Lipoic acid (LA), a dietary supplement known for its strong antioxidant and anti-inflammatory potential, faces challenges due to its poor aqueous solubility and thermal instability. To address these issues, herein methyl-beta-cyclodextrin (M-β-CD) was utilized to create inclusion complex (IC) of LA in 1:1 M stoichiometric ratio of M-β-CD to LA. The LA-M-β-CD-IC was further combined with pullulan (PUL), a non-toxic and water-soluble biopolymer, for the development of electrospun nanofibers (NF) by green and sustainable approach. The resulting PUL/LA/M-β-CD NF formed as a self-standing and flexible material with an average diameter of 569 ± 129 nm and encapsulation efficiency of ∼86.90 %. The developed NF demonstrated an accelerated release, quick dissolution, and disintegration when exposed to artificial saliva replicating the conditions of oral cavity. PUL/LA/M-β-CD NF attenuated the production of ROS and NO by downregulating pro-inflammatory enzymes (iNOS and COX-2) in lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Moreover, PUL/LA/M-β-CD NF also significantly downregulated the expression of pro-inflammatory cytokines including TNF-α, IL-6, and IL-1β along with suppression of NF-ĸB nuclear translocation in comparison to LA (at 250 μM). In nutshell, PUL/LA/M-β-CD NF demonstrated great potential as a rapid disintegrating delivery system for oral anti-inflammatory treatment due to the enhanced physicochemical characteristics of LA.