Avanafil Liposomes as Transdermal Drug Delivery for Erectile Dysfunction Treatment: Preparation, Characterization, and In vitro, Ex vivo and In vivo Studies

Purpose: To formulate avanafil, a recently approved phosphodiesterase-5 enzyme inhibitor, in liposomal form for enhanced transdermal permeation and bioavailability
Methods: Two preparation procedures were employed, leading to the formation of multilamellar vesicles (MLVs) and reverse-phase evaporation unilamellar vesicles (ULVs). The effects of the preparation method and lipid content on the encapsulation efficiency and particle size were studied. Studies assessing the stability, in vitro release, ex vivo permeation and in vivo bioavailability were also conducted in rats.
Results: The preparation of avanafil liposomes as MLVs, the addition of cholesterol, and the use of more rigid phospholipids all increased the avanafil encapsulation efficiency within the liposomes (95.61 %). The stability studies revealed that the liposomes prepared using phospholipids with higher transition temperatures (dipalmitoyl-L-α-phospatidylcholine) were significantly more stable for a longer period of time after storage at 25 ± 0.5 ˚C and 60 ± 5 % relative humidity for a period of 2 months (p < 0.05). In vivo pharmacokinetic results from rats showed a significant increase in the bioavailability of avanafil from transdermal liposomal formulations of up to 7-fold (p < 0.05) compared to the topical drug suspension.
Conclusion: The developed avanafil liposomes represent a promising transdermal drug delivery system for the treatment of erectile dysfunction.

Keywords
Avanafil; Liposomes; Entrapment efficiency; Dipalmitoyl-L-α-phospatidylcholine; Erectile dysfunction