Exploiting Ascorbyl Palmitate Assisted-Chondroitin Sulfate /Chitosan Nanoparticles for Intra-articular Delivery of Lipoic Acid

Abstract

The objective of this study was to explore the anti-arthritic potential of lipoic acid (LA) with antioxidant and anti-inflammatory effects via developing nanoparticles (NPs) based on chitosan (CH) and chondroitin sulfate (CS). The impact of the auxiliary amphiphilic non-surfactant; ascorbyl palmitate (AP) was investigated on the colloidal parameters of CH based NPs and compared with the commonly utilized amphiphilic surfactant; lecithin (L). The proposed nanoparticles (CS/CH NPs) were characterized for colloidal properties (particle size and zeta potential), entrapment efficiency, morphology, physical state of LA and its interaction with the polymeric matrix, in vitro release and antioxidant potential. Adjuvant-induced arthritic model in rats was established and the histopathological states of knee joints were checked. Joint tissue homogenate levels of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), superoxide dismutase (SOD) and malondialdehyde (MDA) were also determined. The prepared NPs containing AP (AP-CS/CH NPS) with a positive surface charge showed significantly reduced particle size and higher LA entrapment relative to those containing L (261.22 nm versus 304.62 nm and 70.65% versus 65.10%). For LA loaded AP-CS/CH NPS, sustained LA release over 1-week period and substantial antioxidant potential were verified. The in vivo results revealed that the proposed NPs exhibited higher inhibition of inflammation than those lacking AP (51.04% versus 35.88% at the 21st day of treatment respectively) with a down-regulation of TNF-α and up-regulation of IL-10. An appreciable boost in SOD and a decline in MDA levels were also detected. Thus, the developed LA loaded nanoformulation could be a promising candidate in anti-arthritis therapy.

Keywords

• Lipoic acid
• Chitosan
• Chondroitin sulfate
• Ascorbyl palmitate
• Nanoparticles
• Arthritis