The purpose of this study was to develop and evaluate topical formulations of
Spantide II, a
neurokinin-1 receptor (NK-1R) antagonist, for the treatment of inflammatory skin disorders.
Spantide II lotion and gel was formulated with and without
n-methyl-2-pyrrolidone (NMP) as a penetration enhancer. The release of
Spantide II from
gels was evaluated using microporous
polyethylene and
polypropylene membranes in a Franz Diffusion cell setup. In vitro percutaneous absorption of
Spantide II from lotion and gel formulations was evaluated using the above setup by replacing the membranes with hairless rat skin. The in vivo anti-inflammatory activity of
Spantide II formulations was evaluated in an
allergic contact dermatitis (ACD) mouse model. Among different
gels studied, PF127 gel showed highest (70-fold) release of
Spantide II compared with
hydroxypropyl methylcellulose (HPMC) and
hydroxypropyl cellulose (HPC)
gels. Lotion and gel formulations with or without NMP showed no detectable levels of
Spantide II in the receiver compartment of the Franz diffusion cell until 24 hours. However,
Spantide II showed significant retention in epidermis and dermis from lotion and gel formulations at 24 hours. The dermal levels increased approximately 3.5- and 2-fold when the lotion and gel formulations contained NMP as compared with the formulation with no NMP (P < .05). The in vivo studies indicated that
Spantide II formulations with NMP were effective in significantly reducing ACD response, similar to
dexamethasone (0.5 mM). In conclusion,
Spantide II was stable as a topical formulation and delivered to target skin tissue (epidermis and dermis) for the treatment of ACD. In addition this study supports the role of cutaneous neurosensory system in modulating inflammatory responses in the skin.