In vitro and in vivo evaluation of topical formulations of Spantide II

Abstract

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.

Skin permeating nanogel for the cutaneous co-delivery of two anti-inflammatory drugs

“…These results are comparable with previous reports from our laboratory, where SP was not detected in the receiver compartment upon application of SP lotion and gel on the rat skin [35]. SC, epidermal and dermal retention of SP for SP-SPN was 7.34, 5.32 and 1.14 mg/g of skin, respectively (Figure 3a).…”

“…ACD, an acute inflammation, is characterized by classical symptoms such as heat, redness, swelling and pain [42]. DNFB induced edema (after secondary exposure) is widely used for investigating cutaneous inflammatory process [35]. Further, IMQ has been reported to induce skin inflammation in mice along with the features of human psoriasis where cytokines like IL-23 and IL-17 levels are elevated with typical phenotypic and histological characteristics [28, 43–45].…”

Transport of Substances and Nanoparticles across the Skin and in Vitro Models to Evaluate Skin Permeation and/or Penetration

“…As sources of membranes, the use of rat, mouse, guinea pig and rabbit skin has been reported. Although it is known that rat skin is around 10 times more permeable than the human skin [27,64,65] its use for in vitro experiments is still common in toxicity studies, making in vitro-in vivo correlations possible [64,66]. Furthermore, a correlation between the skin diffusion coefficients for nortriptyline was observed on comparing Wistar rat skin and human heat-separated epidermis [67].…”

Newly Developed Topical Cefotaxime Sodium Hydrogels: Antibacterial Activity andIn VivoEvaluation

“…These preparations are designed to be administered either orally or parenterally or topically. Topical preparations have several benefits compared with systemic therapy [1, 2]. Initially, the required concentration for antibiotic activity at the skin target site may be more easily achieved after topical dosing.…”