Fatty Acid Esters of G₀-(Propyl Ether Imine) Dendron as Bicephalous Heterolipids for Permeation Enhancement in Transdermal Drug Delivery

The objective of the present study was to synthesize, evaluate, and explore the potential of a new class of bicephalous heterolipids (BHLs) as chemical permeation enhancers (CPEs) with emphasis on investigation of the influence of variable chain lengths of BHLs with the G0-PETIM (poly(propyl ether imine)) dendron as a headgroup on skin permeation efficiency using diclofenac sodium (DS) as a model drug. These BHLs were synthesized, and chemical structures were confirmed by FT-IR, 1H NMR, 13C NMR, and ESI-MS. All BHLs were assessed for in vitro cytotoxicity and in vivo skin irritation studies that revealed their dermal safety. All respective DS gels with loaded BHLs were evaluated for skin permeation at varied concentrations, where gels with 1% concentration showed a significant increase in steady state flux (ERflux) as compared to the control gel and oleic acid loaded gel. The mechanism of enhanced skin permeation using BHL-loaded DS gels was examined using transepithelial electrical resistance (TEER), attenuated total reflection infrared (ATIR), and histomorphology, which showed significant reduction in the barrier integrity, alterations in the stratum corneum (SC), and compromising of the SC. These observations were concurrent with skin permeation results indicating that BHL enhancers could have wide scope as semisynthetic CPEs for transdermal drug delivery.