壳聚糖修饰栀子苷聚乳酸-羟基乙酸纳米粒的制备及经鼻入脑的靶向性

Study on preparation of geniposide chitosan-coated poly lactic acid-glycolic acid nanoparticles and intranasal cavity delivery for brain targeting

目的制备经壳聚糖修饰的栀子苷聚乳酸-羟基乙酸纳米粒(栀子苷CS-PLGA-NPs),并初步评价其鼻腔给药的脑内递药特性。方法采用复乳-溶剂蒸发法制备栀子苷CS-PLGA-NPs,测定其粒径大小、Zeta电位、稳定性及鼻纤毛毒性。并以聚乳酸-羟基乙酸纳米粒(栀子苷PLGA-NPs)为对照,比较2种纳米粒大鼠鼻腔给药后各脑组织及血浆中的药物浓度。结果栀子苷CS-PLGA-NPs形态圆整,粒径(204.3±s 2.4)nm,Zeta电位(5.1±0.7)mV,在鼻洗液中稳定,无鼻纤毛毒性。大鼠鼻腔给予2种纳米粒后,栀子苷CS-PLGA-NPs在各脑组织的AUC0～360min为栀子苷PLGA-NPs的1.19～1.49倍,且各脑组织与血浆AUC的比值明显高于栀子苷PLGA-NPs(P<0.01)。结论 CS-PLGA-NPs能促进药物经鼻腔直接转运入脑,有望作为鼻腔给药的理想载体。

AIM To prepare chitosan-coated poly lacticoglycolic acid nanoparticles of geniposide（CS-PLGA-NPs of geniposide） and primarily evaluate the characteristics of nasal delivery for intracerebral targeting.METHODS CS-PLGA-NPs of geniposide was prepared by a double-emulsion evaporation technique and characterized in terms of size,zeta potential,stability and nasal ciliotoxicity.Taking another kind of nanoparticles of poly lactic acid-glycolic acid（PLGA-NPS） as the control,both of the mentioned preparations the nanoparticles were administered intranasally to rats,and then the concentrations in plasma and brain tissues were monitored and compared respectively.RESULTS CS-PLGA-NPs of geniposide was generally spherical in shape with a mean diameter of（204.3 ± s 2.4） nm,a positive surface charge（5.1 ± 0.7） mV and no ciliotoxicity.The intranasal administration of CS-PLGA-NPs of geniposide resulted in a 1.19-1.49 fold increase of AUC0-360 min in brain tissues,then that of PLGA-NPs of geniposide outcoming with the ratios of AUC in brain tissues and that in plasma of CS-PLGA-NPs of geniposide were significant higher than those of PLGA-NPs（P 0.01）.CONCLUSION CS-PLGA-NPs possess the potential for promoting the efficiency of direct trans nasal cavity cerebral administration of drug and thus be the indeal vehicle for cerebral targeting treatment.