新型喜树碱纳米凝胶的制备与评价及其抗银屑病作用的研究

Preparation and Evaluation of a Novel Camptothecin-loaded Nano Gel and Its Anti-psoriasis Effect

目的制备一种新型喜树碱纳米凝胶以克服银屑病皮肤的角质层屏障;对该新型纳米颗粒体外药物的释放和渗透进行评价,并结合动物模型初步评估其抗银屑病作用。方法将喜树碱包封于聚乳酸-乙醇酸,表面包裹油酸修饰的聚酰胺胺聚合物,得到新型喜树碱纳米颗粒。再将羟丙基甲基纤维素与新型喜树碱纳米颗粒混合搅拌即得新型喜树碱纳米凝胶。结果新型喜树碱纳米颗粒呈球形,单分散,粒径为(238.7±6.6)nm,载药量为(15.4±3.2)μg·mg-1,包封率为(77.8±7.2)%。新型喜树碱纳米凝胶中的药物以缓慢且受控的方式释放,24h内释放59%,皮肤渗透性是对照组的8.50倍,皮肤驻留量是对照组的8.74倍。此外,新型喜树碱纳米凝胶降低了银屑病模型小鼠的银屑病面积严重指数评分及皮褶厚度。喜树碱纳米凝胶各治疗组中,过度角化和角化不全的迹象微弱。结论新型喜树碱纳米颗粒可促进角膜层的水化作用和相应的渗透性;新型喜树碱纳米凝胶是喜树碱经皮给药的有效载体,具有较高的治疗效率,提示该纳米给药系统可能为银屑病提供一种潜在的治疗方法。

Objective To prepare a novel camptothecin-loaded nanogel that can overcome the stratum corneum barrier of the psoriatic skin,study the release and permeation of the novel nanoparticles in vitro,and to evaluate its anti-psoriasis effect using animal models.Methods Camptothecin was encapsulated in polylactic-glycolic acid,and oleic acid modified polyamidoamine was coated on the surface to obtain a new type of camptothecin-loaded nanoparticles.Hydroxypropyl methylcellulose and camptothecin-loaded nanoparticles were mixed and stirred to obtain a new type of camptothecin-loaded nanogel.Results Camptothecin-loaded nanoparticles were spherical and monodisperse,with a particle size of(238.7±6.6)nm,a drug loading of(15.4±3.2)μg·mg-1,and an encapsulation efficiency of(77.8±7.2)%.The drug in this camptothecin-loaded nanogel was released in a slow and controlled manner,59%of the drug was released within 24 hours,the skin permeability was 8.50 times that of the control group,and the skin retention was 8.74 times as high as in the control group.In addition,camptothecin-loaded nanogel reduced the area of psoriasis,scores of severity indexes and skinfold thickness of model mice with psoriasis.The signs of hyperkeratosis and dyskeratosis were weak in each treatment group.Conclusion Camptothecin-loaded nanoparticles can promote the hydration and corresponding permeability of the corneal layer.Camptothecin-loaded nanogel is an effective carrier for transdermal delivery of camptothecin with high therapeutic efficiency,suggesting that the nano-delivery system may provide a potential treatment for psoriasis.