Quantitative structure property relationship assisted development of Fluocinolone acetonide loaded transfersomes for targeted delivery

Abstract

Fluocinolone acetonide (FA) is a corticosteroid, synthetic hydrocortisone used to reduce skin inflammation and itching in psoriasis. The present study investigate the formulation of nanotransfersomes containing FA (FA-NTs) using Quantitative Structure Property Relationship (QSPR) and Box–Behnken approach. FA-NTs containing phospholipid, edge activator and cholesterol in definite ratio were prepared by high pressure homogenization and optimized using Box–Behnken design. Based on the QSPR analysis, Phospholipon 90H was selected for nanotransfersome form along with sodium deoxycholate as edge activator. The impact of independent variables Phospholipid concentration (X1), sodium deoxycholate (X2) and number of homogenization cycles (X3) on dependent variables viz., particle size and entrapment efficiency (%EE) were studied. The optimized nanotransfersomal formulation was characterized for FTIR, XRD, DSC, particle size, zeta potential, entrapment efficiency, in-vitro release and ex-vivo permeation studies. FA-NTs batch evidenced 92 ± 4% entrapment efficiency and showed 29.9 nm particle size, 0.264 polydispersity index and −23.72 mV zeta potential. FA-NTs exhibited 68% drug release within 24 h and followed Higuchi release kinetic model (R2 = 0.9902). FA-NTs showed 22.56 μg/cm2/h transdermal flux with 12.40 fold higher than FA dispersion. Biologically, FA-NTs showed hyperproliferation inhibition of differentiated HaCaT cells as evidenced from cell viability, antiproliferative action, nitric oxide production, proinflammatory cytokine measurement, Quantitative Real time PCR and cellular uptake studies. Thus, the present study demonstrates the successful use of QSPR studies and Box–Behnken design in the preparation of nanotransfersomes for efficient delivery of FA in the management of psoriasis.