Graduate Institute of Biomedical Sciences, Chang Gung University, Kweishan, Taoyuan, Taiwan.
Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan; Research Center for Food and Cosmetic Safety and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan.
Acta Biomater. 2019 May;90:350-361. doi: 10.1016/j.actbio.2019.04.002. Epub 2019 Apr 3.
Both phosphodiesterase (PDE4) inhibitors and omega-9 fatty acids show anti-inflammatory activity for treating inflamed skin diseases, but their efficacy remains low. Combinatorial agents are anticipated to offer an advanced strategy for efficient therapy. We prepared cilomilast-loaded oleic acid (OA) nanocarriers to test the inhibitory capability against human neutrophil stimulation and a murine psoriasis model. OA played dual roles in the nanocarriers as both the active ingredient and lipid matrix in the nanoparticulate core. OA nanoparticles but not free OA could restrain calcium mobilization in activated neutrophils. The inhibition level of superoxide anion and elastase by cilomilast-loaded OA nanocarriers approximated that of free forms. In the mouse model, the intradermal nanosystems reduced imiquimod-induced epidermal thickening from 230.4 to 63.1 μm. Transepidermal water loss was decreased from 30.2 to 11.3 g/m/h by integrated nanocarriers. The nanosystems mitigated neutrophil infiltration and hyperproliferation in the psoriasiform lesion via decreased expression of cytokines and chemokines. STATEMENT OF SIGNIFICANCE: The long-term therapy for psoriasis is unsatisfactory due to the possible adverse effects and inefficiency after prolonged use. Both phosphodiesterase (PDE4) inhibitors and omega-9 fatty acids such as oleic acid (OA) show anti-inflammatory activity for treating inflamed skin diseases. Combinatorial agents are anticipated to offer an advanced strategy for efficient therapy. OA is also ideal for incorporation into nanoparticles to enhance particulate emulsification, drug entrapment, and biocompatibility. We prepared cilomilast-loaded oleic acid (OA) nanocarriers to test the inhibitory capability against human neutrophil stimulation and a murine psoriasis lesion. OA nanocarriers are indigenous to prevent neutrophil activation and the deterioration of psoriatic lesion. Cilomilast incorporation in OA nanocarriers could further mitigate the clinical score and suppressing proinflammatory mediators.
磷酸二酯酶 (PDE4) 抑制剂和 ω-9 脂肪酸都具有抗炎活性，可用于治疗炎症性皮肤病，但疗效仍较低。组合药物有望为有效治疗提供一种先进策略。我们制备了西罗莫司负载油酸 (OA) 纳米载体，以测试其对人中性粒细胞刺激和小鼠银屑病模型的抑制能力。OA 在纳米载体中同时发挥活性成分和纳米颗粒核心中脂质基质的双重作用。OA 纳米颗粒而非游离 OA 可抑制激活中性粒细胞中的钙动员。西罗莫司负载 OA 纳米载体对超氧阴离子和弹性蛋白酶的抑制水平接近游离形式。在小鼠模型中，皮内纳米系统将咪喹莫特诱导的表皮增厚从 230.4μm 减少至 63.1μm。通过整合纳米载体，经皮水分丢失从 30.2g/m/h 减少至 11.3g/m/h。纳米系统通过降低细胞因子和趋化因子的表达，减轻银屑病样病变中的中性粒细胞浸润和过度增殖。
由于长期使用可能产生的不良反应和效率低下，银屑病的长期治疗效果并不令人满意。磷酸二酯酶 (PDE4) 抑制剂和 ω-9 脂肪酸（如油酸 (OA)）都具有抗炎活性，可用于治疗炎症性皮肤病。组合药物有望为有效治疗提供一种先进策略。OA 也非常适合纳入纳米颗粒，以增强颗粒乳化、药物包封和生物相容性。我们制备了西罗莫司负载油酸 (OA) 纳米载体，以测试其对人中性粒细胞刺激和小鼠银屑病病变的抑制能力。OA 纳米载体可天然阻止中性粒细胞活化和银屑病病变恶化。西罗莫司负载 OA 纳米载体可进一步减轻临床评分并抑制促炎介质。
