新型喜树碱纳米凝胶给药系统的构建及体外透皮特性研究

Novel camptothecin loaded nanogel system:formulation optimization and in vitro transdermal permeability study

目的制备新型喜树碱纳米凝胶给药系统(CPT-PPO gel),并对其含量、理化性质和体外透皮特性进行考察。方法以乙交酯-丙交酯共聚物(PLGA)包裹抗银屑病药物喜树碱(CPT)作为纳米系统的核,将聚酰胺-胺(PAMAM,G3.0)包裹在PLGA表面作为纳米系统的壳,采用乳化溶剂挥发法制备载喜树碱纳米系统(CPT-PLGA-PAMAM,CPT-PP),并用油酸(OA)进行修饰,得到经表面改性的核壳纳米给药系统(CPT-PLGA-PAMAM-OA,CPT-PPO)。采用HPLC法测定纳米乳中喜树碱的含量,采用透射电镜和激光粒径测定仪分别考察纳米粒的形态和粒径。以羟丙甲基纤维素(HPMC)为基质,制备CPT-PPO gel,并采用Franz扩散池对其体外透皮特性进行考察。结果制得的CPT-PPO gel平均粒径为(246.7±5.4)nm,包封率为(78.7±6.9)%,含量稳定,在4℃时具有良好的稳定性。体外透皮实验表明,纳米凝胶CPT-PPO gel、CPTPP gel比普通凝胶CPT gel有更高的皮肤渗透量和滞留量(P<0.01),且CPT-PPO gel在皮肤渗透量和滞留量上均显著高于CPT-PP gel(P<0.05)。结论经过OA修饰的CPT-PPO gel可以显著提高药物的皮肤吸收量和滞留量,有望成为应用CPT局部治疗银屑病的新剂型。

Objective To prepare a novel drug delivery system camptothecin loaded nanogel（CPT-PPO gel）,and investigate its contents,physical and chemical properties and in vitro transdermal permeability.Methods The solvent evaporation method was utilized to prepare core-shell nano-drug delivery systems（CPT-PLGA-PAMAM,CPT-PP）,in which the Poly lactic-co-glycolic acid（PLGA）was used to load camptothecin as the nucleus and the polyamidoamine（PAMAM）G3.0 was wrapped in the surface of PLGA as the shell.Then the oleic acid（OA）was connected to CPT-PP to obtain the surface modified drug delivery system（CPT-PLGA-PAMAM OA,CPT-PPO）.HPLC was used to determine the content of camptothecin in nanoparticles,transmission electron microscopy was applied to identify the nanoparticles morphology,and laser analyzer was used to determine the particle size.The hydroxypropyl methylcellulose（HPMC）was added as the base for the preparation of the nanogel（CPT-PPO gel）at last.The Franz-diffusion cell was used to determine the permeation rate of nanogel in vitro.Results The resulting CPT-PPO gel was stable at 4℃,the average particle size was（246.7± 5.4）nm and the encapsulation efficiency was up to（78.7±6.9）%.Comparing to the normal gel,（CPT gel）,the cumulative penetration amount and the retention amount in the skin of the nanogels（CPT-PPO gel,CPT-PP gel）were significant higher（P0.01）,the retention and cumulative penetration amount of CPT-PPO gel was significant higher than that of CPT-PP gel（P0.05）.Conclusion After modified by OA,CPT-PPO gel can increase the cumulated amount and absorption in skin and can be used as a carrier of CPT in the new formulation for topical treatment of psoriasis.