Exploration of skin permeation mechanism of frusemide with proniosomes.

The present study explored the transdermal permeation enhancing mechanism of non-ionic surfactant vesicles (proniosomes) of frusemide across rat skin. Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), activation energy and histological examination were carried out to study the mode of action of the optimized proniosome formulations PGS [Span 40:soyalecithin:cholesterol (4.5:4.5:1)] and PGD [Span 40:dicetylphosphate:cholesterol (4.5:4.5:1)]. The IR spectra showed a prominent decrease in peak areas and heights of CH2 stretchings but did not show shift of these peaks and shift in amide bands. DSC studies also confirmed the IR findings. It was concluded that the proniosomes disrupted the lipid bilayer by extracting the lipids thereby creating pathways for drug penetration. The significant decrease in activation energy for frusemide permeation across rat skin indicated the SC lipid bilayers were significantly disrupted (p<0.05). Histological investigations were carried out. Disruption and extraction of lipid bilayers as distinct voids and empty spaces were visible in the epidermal region. Overall, our findings suggested that proniosomal formulations offer a promising means for non-invasive delivery of frusemide, especially due to their ability to modulate drug transfer and serve as non-toxic permeation enhancers.