补骨脂素PLGA纳米粒的制备及对人体皮肤的渗透特性

Preparations of Psoralen-Loaded PLGA Nanoparticles and Its Characteristics of Penetration Across Human Skin

目的制备外用的载有补骨脂素的PLGA纳米粒,为临床上改进PUVA疗法降低其毒副作用奠定基础。方法采用溶剂置换-界面聚合物沉积法制备补骨脂素纳米粒。通过建立包封率测定方法,并结合其外观光学特征,优化出补骨脂素纳米粒的处方组成。并考查其物理化学特性以及在体外人工半透膜的释放特性和人体完整皮肤的渗透特性。结果优化条件下制备出的纳米粒平均粒径为(107.16±0.17)nm,粒径分布系数为(0.052±0.004),Zeta电位为(-8.82±0.28)mV,包封率为(83.62±1.98)%。在体外人工半透膜中的释放特性表明,该补骨脂素纳米粒具有良好的释放性能,24 h内释放率达75.84%。在人体皮肤中的渗透动力学特征表明,相比较于乙醇溶液制剂,该纳米粒在人体皮肤具有明显的缓控释特征,且能增加在人体皮肤中的贮存量。结论优化条件制备出的补骨脂素皮肤用纳米粒载药系统有可能成为临床上改进补骨素光化学疗法降低其毒副作用的一种新的经皮给药制剂。

OBJECTIVE To develope and characterize psoralen loaded PLGA nanoparticles for topical formulation,with the final goal of reducing the toxicity and improving the efficacy of PUVA therapy.METHODS Psoralen loaded PLGA nanoparticles were prepared by interfacial polymer deposition following solvent displacement.The formulation was optimized according to its encapsulation efficiency and optical characterisation.The following characteristics of nanoparticle formulations optimised were determined： particle size,Zeta potential,encapsulation efficiency,in vitro released profiles across dialysis membrane,ex-vivo skin permeation and stockage behaviour.RESULTS The nonoparticles were optimized.The mean diameter was（107.16±0.17）nm,polydispersity index was（0.052±0.004）,and Zeta potential was（-8.82±0.28） mV.Its encapsulation efficiency was（83.62±1.98）%.The release of psoralen from nanoparticles was good,and significantly faster than EtOH formulation.The results of skin permeation and stockage proved that controlled release of psoralen PLGA-nanoparticles increased drug content in the skin,while maintaining moderate percutaneous absorption.CONCLUSION Psoralen loaded PLGA nanospartilcles might be a promising transdermal delivery system in order to improve the efficacy and reduce the side effects in the PUVA therapy.