Comparative study of liposomes, ethosomes and transfersomes as carriers for enhancing the transdermal delivery of diflunisal: In vitro and in vivo evaluation

The current study aimed to develop an effective transdermal nanovesicular carrier of diflunisal that provides enhanced delivery through the skin. Two types of nanovesicles, ethosomes and transfersomes, were investigated and compared to conventional liposomes. Ethosomes with variable ethanol contents (10, 30 and 50%) and transfersomes using different edge activators, including sodium deoxycholate, sodium cholate and sodium taurocholate, were prepared and characterized. The obtained vesicles revealed good entrapment efficiencies (46.73-65.99%), nanometric vesicle sizes (453.10-796.80 nm) and negative zeta potential values (-45.40 to -86.90 mV). Ethosomes with 30% ethanol and sodium deoxycholate-containing transfersomes were incorporated into hydrogels to evaluate their in vitro release and permeation patterns. Nanovesicular hydrogels exhibited more sustained diflunisal release than did corresponding dispersions. Compared to liposomal hydrogel, both carriers proved the superiority of diflunisal permeation and flux across the skin. Confocal laser scanning microscopy showed improved penetration of rhodamine-loaded nanovesicles through skin layers with a wider distribution and higher fluorescence intensity. Compared to liposomes, selected nanovesicles exhibited remarkable antinociceptive and anti-inflammatory effects manifested by significant reduction in number of writhings and significantly higher inhibition of paw oedema. Hence, the developed nanovesicles could be considered promising carriers for transdermal delivery of diflunisal for pain and inflammation management.