Şenyiğit Taner, Sonvico Fabio, Rossi Alessandra, Tekmen Işıl, Santi Patrizia, Colombo Paolo, Nicoli Sara, Özer Özgen
Department of Pharmaceutical Technology, Faculty of Pharmacy, Ege University, Bornova, 35100 Izmir, Turkey.
Department of Pharmacy, University of Parma, 43124 Parma, Italy.
Int J Mol Sci. 2016 Dec 26;18(1):32. doi: 10.3390/ijms18010032.
The aim of this work was to assess in vivo the anti-inflammatory efficacy and tolerability of clobetasol propionate (CP) loaded lecithin/chitosan nanoparticles incorporated into chitosan gel for topical application (CP 0.005%). As a comparison, a commercial cream (CP 0.05% /), and a sodium deoxycholate gel (CP 0.05% /) were also evaluated. Lecithin/chitosan nanoparticles were prepared by self-assembling of the components obtained by direct injection of soybean lecithin alcoholic solution containing CP into chitosan aqueous solution. Nanoparticles obtained had a particle size around 250 nm, narrow distribution (polydispersity index below 0.2) and positive surface charge, provided by a superficial layer of the cationic polymer. The nanoparticle suspension was then loaded into a chitosan gel, to obtain a final CP concentration of 0.005%. The anti-inflammatory activity was evaluated using carrageenan-induced hind paw edema test on Wistar rats, the effect of formulations on the barrier property of the stratum corneum were determined using transepidermal water loss measurements (TEWL) and histological analysis was performed to evaluate the possible presence of morphological changes. The results obtained indicate that nanoparticle-in-gel formulation produced significantly higher edema inhibition compared to other formulations tested, although it contained ten times less CP. TEWL measurements also revealed that all formulations have no significant disturbance on the barrier function of skin. Furthermore, histological analysis of rat abdominal skin did not show morphological tissue changes nor cell infiltration signs after application of the formulations. Taken together, the present data show that the use of lecithin/chitosan nanoparticles in chitosan gel as a drug carrier significantly improves the risk-benefit ratio as compared with sodium-deoxycholate gel and commercial cream formulations of CP.
本研究旨在体内评估负载丙酸氯倍他索（CP）的卵磷脂/壳聚糖纳米粒（其被掺入壳聚糖凝胶用于局部应用，CP浓度为0.005%）的抗炎功效和耐受性。作为对照，还评估了一种市售乳膏（CP 0.05%）和一种脱氧胆酸钠凝胶（CP 0.05%）。卵磷脂/壳聚糖纳米粒通过将含CP的大豆卵磷脂醇溶液直接注射到壳聚糖水溶液中获得的组分自组装制备而成。所获得的纳米粒粒径约为250 nm，分布窄（多分散指数低于0.2）且表面带正电荷，这由阳离子聚合物的表层提供。然后将纳米粒悬浮液装入壳聚糖凝胶中，以获得最终CP浓度为0.005%。使用角叉菜胶诱导的Wistar大鼠后爪水肿试验评估抗炎活性，使用经皮水分流失测量（TEWL）确定制剂对角质层屏障特性的影响，并进行组织学分析以评估可能存在的形态学变化。所得结果表明，凝胶中纳米粒制剂产生的水肿抑制作用明显高于其他受试制剂，尽管其CP含量低十倍。TEWL测量还显示，所有制剂对皮肤屏障功能均无显著干扰。此外，大鼠腹部皮肤的组织学分析表明，在应用制剂后未显示形态学组织变化或细胞浸润迹象。综上所述，目前的数据表明，与CP的脱氧胆酸钠凝胶和市售乳膏制剂相比，在壳聚糖凝胶中使用卵磷脂/壳聚糖纳米粒作为药物载体可显著改善风险效益比。
