Department of Pharmaceutical Technology, Biopharmaceutics and Nutricosmetics, Freie Universität Berlin, Kelchstrasse 31, 12169 Berlin, Germany.
J Biomed Nanotechnol. 2009 Aug;5(4):437-44. doi: 10.1166/jbn.2009.1054.
PX-18 and PX-13 are new secreted phospholipase A2 inhibitors. An increased expression of secreted phospholipase A2 in psoriatic epidermis and dermis was reported in the literature, hence the dermal application of PX-18 and PX-13 seems to be a promising approach for psoriasis treatment. Both compounds are practically insoluble in aqueous media and hard to formulate using conventional techniques. Therefore, nanosuspensions were prepared by high pressure homogenization. Pre-clinical skin and eye irritation tests were performed with PX-18 and PX-13 bulk material and 5% (w/w) PX-18 and PX-13 nanosuspensions using the EPISKIN and the HET-CAM test to aid safety assessment and to facilitate the design of safe and efficient human studies. It could be shown that nanosuspensions with an active content of 5% (w/w) with a particle size well in the nanometer range can be produced applying high pressure homogenisation. The results of the EPISKIN test allow the classification of PX-18 and PX-13 bulk material and the according nanosuspensions as non irritant to the skin. According to the test protocol applied for the HET-CAM test, the bulk material of the new secreted phospholipase A2 inhibitors as well as the nanosuspensions can be classified as non/slightly irritant to the eye.
PX-18 和 PX-13 是新型分泌型 PLA2 抑制剂。文献报道，在银屑病表皮和真皮中分泌型 PLA2 的表达增加，因此 PX-18 和 PX-13 的皮肤应用似乎是一种有前途的银屑病治疗方法。这两种化合物在水介质中几乎不溶，且难以使用常规技术进行配方。因此，通过高压均质法制备纳米混悬剂。使用 EPISKIN 和 HET-CAM 试验对 PX-18 和 PX-13 原料药和 5%（w/w）的 PX-18 和 PX-13 纳米混悬剂进行了皮肤和眼睛刺激性的预临床前测试，以辅助安全性评估并促进安全有效的人体研究设计。结果表明，通过高压均质化可以生产出活性含量为 5%（w/w）、粒径在纳米范围内的纳米混悬剂。EPISKIN 测试的结果允许将 PX-18 和 PX-13 原料药和相应的纳米混悬剂分类为对皮肤无刺激性。根据 HET-CAM 测试应用的测试方案，新的分泌型 PLA2 抑制剂的原料药和纳米混悬剂可被归类为对眼睛无刺激性/轻度刺激性。
