Topical delivery of cyclodextrin crosslinked nanosponge of anacardic acid for treatment of UV-B induced skin photoaging: Formulation, characterization and biochemical estimation

Photoaging is a complex process that leads to deterioration of the skin upon exposure to solar UV-B radiation resulting in skin aging symptoms like wrinkles, laxity and loss of elasticity, etc. The pathogenesis includes an increased level of reactive oxygen species (ROS), overexpression of histone acetyltransferase (HAT P300), and matrix metalloproteinase (MMP-1) enzymes. Anacardic acid (AnaC15:0) has been reported to have good antioxidant properties, however, poor skin permeation restricts its use as an anti-aging molecule. In the current research, we have developed Anacardic Acid-β-cyclodextrin (β-CD) nanosponge (NS) which can improve the solubility and thus the permeability and antiphotoaging activity of AnaC15:0. The formulation was optimized by using a 3-level factorial design which resulted into the nanosponge with a particle size of 197 ± 11 nm having polydispersity index of 0.276 ± 0.028 and zeta potential −22.1 ± 1.9 mV. The complex formation was confirmed by using FT-IR and XRD studies while the solubility study demonstrated a linear relationship between AnaC15:0 and NS up to 1:3 ratios. Furthermore, AnaC15:0-NS laden gel demonstrated an optimum texture profile (Hardness, adhesiveness, and elasticity). The skin pharmacokinetic study of the developed formulation revealed higher retention of AnaC15:0 in the epidermis and dermis in comparison with the free drug. Furthermore, the in-vivo studies unveiled the remarkable healing potential of AnaC15:0-NS gel by reducing epidermal thickness (confirmed by histopathology), ROS level, and reduced expression of HAT P300 and MMP-1 enzymes significantly (p < 0.005). Data in hand collectively suggest the improved efficacy of the nanosponge gel against photoaging and the formulation approach can be explored further to improve the efficacy of other difficult to deliver drugs.