Dept. Scienze della Vita e dell'Ambiente, Sezione Scienze del Farmaco, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy.
Int J Pharm. 2013 Feb 25;443(1-2):128-36. doi: 10.1016/j.ijpharm.2012.12.041. Epub 2013 Jan 5.
Diclofenac-loaded phospholipid vesicles, namely conventional liposomes, ethosomes and PEVs (penetration enhancer-containing vesicles) were developed and their efficacy in TPA (phorbol ester) induced skin inflammation was examined. Vesicles were made from a cheap and unpurified mixture of phospholipids and diclofenac sodium; Transcutol P and propylene glycol were added to obtain PEVs, and ethanol to produce ethosomes. The structure and lamellar organization of the vesicle bilayer were investigated by transmission electron microscopy and small and wide angle X-ray scattering, as well as the main physico-chemical features. The formulations, along with a diclofenac solution and commercial Voltaren Emulgel, were tested in a comparative trial for anti-inflammatory efficacy on TPA-treated mice dorsal skin. Vesicles were around 100 nm, negatively charged, able to encapsulate diclofenac in good yields, and disclosed different lamellarity, as a function of the formulation composition. Vesicular formulations promoted drug accumulation and reduced the permeation. Administration of vesicular diclofenac on TPA-inflamed skin resulted in marked attenuation of oedema and leucocyte infiltration, especially using PEVs. Histology confirmed the effectiveness of vesicles, since they provided an amelioration of the tissual damage induced by TPA. The proposed approach based on vesicular nanocarriers may hold promising therapeutic value for treating a variety of inflammatory skin disorders.
载有双氯芬酸的磷脂囊泡，即普通脂质体、醇质体和 PEV（含有渗透增强剂的囊泡）被开发出来，并研究了它们在 TPA（佛波酯）诱导的皮肤炎症中的疗效。囊泡由廉价且未纯化的磷脂和双氯芬酸钠混合物制成；添加 Transcutol P 和丙二醇以获得 PEV，并添加乙醇以产生醇质体。通过透射电子显微镜和小角 X 射线散射以及主要的物理化学特性研究了囊泡双层的结构和层状组织。制剂与双氯芬酸钠溶液和商业 Voltaren Emulgel 一起在 TPA 处理的小鼠背部皮肤的抗炎功效比较试验中进行了测试。囊泡约为 100nm，带负电荷，能够以良好的产率包封双氯芬酸钠，并根据制剂组成显示出不同的层状结构。囊泡制剂促进药物积累并减少渗透。将囊泡双氯芬酸钠施用于 TPA 炎症皮肤可显著减轻水肿和白细胞浸润，特别是使用 PEV 时。组织学证实了囊泡的有效性，因为它们改善了 TPA 诱导的组织损伤。基于囊泡纳米载体的这种方法可能对治疗各种炎症性皮肤疾病具有有前途的治疗价值。
