Professional Compounding Centers of America (PCCA), 9901 South Wilcrest Drive, Houston, TX, 77099, USA.
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Arch Dermatol Res. 2020 Mar;312(2):145-154. doi: 10.1007/s00403-019-01981-2. Epub 2019 Oct 30.
Psoriasis is a multifactorial skin disease involving abnormal cell proliferation and inflammation; an efficacious topical treatment is yet to be identified. A formulation containing 1% Naltrexone HCl in XemaTop™ base was compounded, characterized and evaluated in vitro as a possible treatment for psoriasis. A three-dimensional psoriasis tissue model was exposed to the formulation for 2 or 5 days and analyzed for the level of markers of cellular proliferation, and inflammatory cytokine IL-6. Using immunohistochemical staining, the level of Ki67 protein significantly decreased in the drug-treated tissues. Western blot analysis showed 86% and 53% down-regulation of other proliferation markers PCNA and CYCLIN D1, respectively, after 5-day exposure. The pro-survival Wnt/β-catenin pathway was compromised as indicated by 57% decrease in the level of β-CATENIN and down-regulation of its down-stream targets including CYCLIN D1 (decreased by 53%), c-MYC (63%), c-JUN (92%) and MET (96%) proteins. Likewise, the PI3K/AKT/mTOR pathway was significantly inhibited by 1% Naltrexone HCl in XemaTop™, suggesting protein synthesis was affected. The production of IL-6 was inhibited by 70% in drug-treated tissues. These results suggest that the compounded drug is efficacious in down-regulating molecular markers associated with the pathogenesis of psoriasis. Low-dose Naltrexone in XemaTop™ was stable within 180 days when stored under refrigerated or ambient conditions. These results provide a basis for a clinical evaluation of 1% Naltrexone HCl in XemaTop™ in psoriasis patients.
银屑病是一种涉及异常细胞增殖和炎症的多因素皮肤疾病；尚未发现有效的局部治疗方法。我们配制了一种含有 1%盐酸纳曲酮的 XemaTop™基质制剂，并对其进行了体外特性描述和评估，以期将其作为治疗银屑病的潜在方法。将三维银屑病组织模型暴露于该制剂中 2 或 5 天，并分析细胞增殖标志物和炎症细胞因子 IL-6 的水平。通过免疫组织化学染色，药物处理组织中 Ki67 蛋白的水平显著降低。Western blot 分析显示，5 天暴露后，其他增殖标志物 PCNA 和 CYCLIN D1 的下调率分别为 86%和 53%。存活的 Wnt/β-catenin 通路被削弱，β-CATENIN 的水平降低了 57%，其下游靶标包括 CYCLIN D1（降低了 53%）、c-MYC（降低了 63%）、c-JUN（降低了 92%）和 MET（降低了 96%）蛋白。同样，1%盐酸纳曲酮在 XemaTop™中显著抑制了 PI3K/AKT/mTOR 通路，提示蛋白质合成受到影响。药物处理组织中 IL-6 的产生抑制了 70%。这些结果表明，该复合药物在下调与银屑病发病机制相关的分子标志物方面具有疗效。在冷藏或环境条件下储存时，XemaTop™中的低剂量纳曲酮在 180 天内稳定。这些结果为在银屑病患者中评估 1%盐酸纳曲酮在 XemaTop™中的疗效提供了依据。
