Alginate/chitosan/diallyl disulfide nanoparticles: Synthesis, characterization and their anti-inflammatory efficacy on TPA-induced acute mouse ear inflammation

Abstract

Diallyl disulfide (DADS) is a garlic (Allium sativum) derived potent anti-inflammatory compound. Due to poor bioavailability, its biological application has limitations. Nanoencapsulation of therapeutic drugs is a promising approach to increase their bioavailability, specificity, and efficacy. In our approach, DADS was coated with the natural polymers alginate and chitosan into a polyelectrolytic nano-formulation. Characterization of the nanoparticles showed monodispersed nanosized particles and a release study at pH 5.5 revealed sustained release of the drug. To investigate the anti-inflammatory efficacy of the DADS nanoparticle (DADS-NP), a comparative study with the free drug was conducted on a mouse model of 12-O-tetradecanoylphorbol-13-acetate (TPA) induced ear edema. The results indicated that DADS-NP significantly alleviated TPA-induced ear edema more effectively than the free drug of the same concentration. Further, mechanistic studies indicated that DADS-NP more efficiently downregulated the phosphorylation of p38 mitogen activated protein kinase which subsequently restricted the activation and nuclear translocation of downstream transcription factor nuclear factor- кB (NF-кB). This downregulated the expression of pro-inflammatory proteins cyclooxygenase-2 (COX-2) and inducible-nitric oxide synthase (i-NOS) thus mitigating ear edema. Cellular internalization of the DADS-NP was observed. Collectively, our studies indicate enhanced anti-inflammatory efficiency of DADS-NP when compared to free DADS suggesting enhanced stability and bioavailability.