Transdermal Delivery of Capsaicin Nanoemulgel: Optimization, SkinPermeation and In Vivo Activity against Diabetic Neuropathy

Diabetic somatic neuropathy is one of the most prevalent complications in type 1diabetes mellitus (T1D). Many treatments were investigated to alleviate the pain associatedwith this condition. Capsaicin is a naturally occurring lipophilic alkaloid that proved to be aneffective and safe treatment of chronic painful disorders. Despite the known therapeutic benefitsof capsaicin, the conventional topical formulations have limited bioavailability. Therefore, thecurrent study aims to develop capsaicin nanoemulgel to increase skin permeation and enhanceits activity against neuropathic pain.

Low-energy emulsification method was used to prepare nanoemulsions, usingeucalyptus oil as the oily phase, Tween 80 as a surfactant, propylene glycol, ethanol andisopropyl alcohol as co-surfactants. Pseudo-ternary phase diagrams were constructed toinvestigate and optimize the formulation. Subsequently, the optimum formulation wasformulated as a nanoemulgel and investigated for, skin permeation using Franz diffusion cell,and diabetic neuropathy (DN) management using alloxan-induced diabetic mice.

The selected nanoemulsion containing 0.05% capsaicin is composed of 8 % oil,24 % Smix (Tween 80: isopropyl alcohol 2:1 w/w) and 68 % water. It is characterized bynanosized globules (28.15 ± 0.24 nm) with a relatively low polydispersity index (0.27 ± 0.05).The nanoemulgel revealed circa 4-fold increase in capsaicin cumulative permeation whencompared to the conventional gel, and an improvement in its antinociceptive properties wasobserved in the treated diabetic mice (P < 0.05).

The selected capsaicin nanoemulgel would be a promising transdermal formulationthat may alleviate diabetic neuropathy in T1D patients.