论文部分内容阅读
目的考察亲水性多肽类药物神经毒素自组装核壳型纳米粒(self-assembled neurotoxin-loaded nanoparticles of core-shelltype,NT-SAN)大鼠鼻黏膜给药后脑内药动学特征。方法以异硫氰酸荧光素标记NT(FITC-NT),采用聚乙二醇-g-聚氰基丙烯酸乙酯嵌段共聚物(PEG-g-PECA)为载体,乳化聚合法制备FITC-NT-SAN。采用大鼠脑微透析技术及荧光分光光度法,以FITC-NT-SAN和FITC-NT溶液肌内注射给药为对照,连续测定FITC-NT-SAN经鼻黏膜给药后FITC-NT在大鼠中脑导水管周围灰质(periaqueductal gray,PAG)部位浓度的经时变化。结果 FITC-NT-SAN呈圆形或类圆形,大小均匀,平均粒径为(89.6±8.9)nm,包封率为(58.43±0.62)%。FITC-NT-SAN经鼻黏膜给药后在PAG的FITC-NT浓度均明显高于FITC-NT-SAN和FITC-NT溶液的肌内注射给药(P<0.01),ρmax、tmax和AUC0-∞分别为(89.26±7.58)ng.mL-1、120.00 min和(26 320.88±1 007.74)ng.min.mL-1,相对生物利用度为137.28%。结论以PEG-g-PECA为载体的FITC-NT-SAN经鼻黏膜给药有助于提高NT的脑内浓度及生物利用度,该结果为研究适宜蛋白质多肽类等大分子药物经鼻黏膜给药的脑靶向新剂型提供参考。
Objective To investigate the intracranial pharmacokinetics of self-assembled neurotoxin-loaded nanoparticles of core-shell type (NT-SAN) in rats after nasal mucosa administration. Methods FITC-NT was labeled with fluorescein isothiocyanate (FITC-NT). PEG-g-PECA was used as a carrier to prepare FITC- NT-SAN. The intracranial injection of FITC-NT-SAN and FITC-NT solution was used as a control, using rat brain microdialysis technology and fluorescence spectrophotometry. FITC-NT was continuously measured after nasal mucosa administration of FITC-NT-SAN Time-dependent changes in the concentration of periaqueductal gray (PAG) in rat midbrain. Results The FITC-NT-SAN was round or round and uniform in size. The mean particle size was (89.6 ± 8.9) nm and the entrapment efficiency was (58.43 ± 0.62)%. The concentrations of FITC-NT in PAG after nasal mucosa administration in FITC-NT-SAN group were significantly higher than those in FITC-NT-SAN and FITC-NT group (P <0.01), while pmax, tmax and AUC0- ∞ were (89.26 ± 7.58) ng.mL-1,120.00 min and (26 320.88 ± 1 007.74) ng.min.mL-1, respectively. The relative bioavailability was 137.28%. Conclusions Administration of FITC-NT-SAN via nasal mucosa with PEG-g-PECA as a carrier may improve brain concentration and bioavailability of NT. This study was conducted to investigate the effect of nasal mucosa on macrophages such as protein peptides Drug targeting brain new formulations provide a reference.