School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China.
Int J Pharm. 2010 Feb 15;386(1-2):249-55. doi: 10.1016/j.ijpharm.2009.11.002. Epub 2009 Nov 10.
Anti-neuroexcitation peptide (ANEP) is a promising candidate for the treatment of neuroexcitation-associated diseases. N-Trimethyl chitosan (TMC) with different degrees of quaternization was synthesized, characterized and evaluated as a brain-targeting delivery vehicle for ANEP. ANEP-loaded TMC nanoparticles were prepared by ionic crosslinking of TMC with tripolyphosphate (TPP). The optimized formulation of nanoparticles consisted of TMC with a degree of quaternization (DQ) of 36.1% and TPP solution with a concentration of 0.6 mg/mL. The mean encapsulation efficiency and loading capacity of the optimum formulation was 80.63% and 185.4 microg/mL, respectively, while the mean particle size, zeta potential, and pH value were 255 nm, 32.0 mV and 6.61, respectively. ANEP was labeled with FITC for in vivo tissue distribution experiments. The results showed that the targetability of ANEP to brain was significantly increased by TMC nanoparticles. Absorptive-mediated transcytosis was believed to be the main pathway for the brain-targeting of FITC-ANEP-TMC/NPs. These findings demonstrate that TMC nanoparticles are potentially useful brain-targeting delivery systems for ANEP.
抗神经兴奋肽（ANEP）是治疗神经兴奋相关疾病的有前途的候选药物。合成了不同季铵化程度的 N-三甲基壳聚糖（TMC），并将其作为 ANEP 的脑靶向递药载体进行了表征和评价。通过 TMC 与三聚磷酸（TPP）的离子交联制备了载有 ANEP 的 TMC 纳米粒。纳米粒的最佳配方由季铵化度（DQ）为 36.1%的 TMC 和浓度为 0.6mg/mL 的 TPP 溶液组成。最佳配方的平均包封效率和载药量分别为 80.63%和 185.4μg/mL，而平均粒径、Zeta 电位和 pH 值分别为 255nm、32.0mV 和 6.61。用 FITC 标记 ANEP 进行体内组织分布实验。结果表明，TMC 纳米粒显著增加了 ANEP 向脑的靶向性。吸收介导的转胞吞作用被认为是 FITC-ANEP-TMC/NPs 脑靶向的主要途径。这些发现表明 TMC 纳米粒是 ANEP 潜在有用的脑靶向递药系统。
