چکیده (انگلیسی):

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 ~3.5- and 2-fold when the lotion and gel
formulations contained NMP as compared with the
formulation with no NMP (P G .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.