Evaluation of neuropeptide loaded trimethyl chitosan nanoparticles for nose to brain delivery
Evaluation of neuropeptide loaded trimethyl chitosan nanoparticles for nose to brain delivery
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DOI：
10.1016/j.ijbiomac.2013.06.041
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发表时间：
2013-10-01
影响因子：
8.2
通讯作者：
Madan, Jitender
中科院分区：
文献类型：
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作者：
Kumar, Manoj;Pandey, Ravi Shankar;Madan, Jitender
亮氨酸脑啡肽（Leu-Enk）是痛觉传递中的一种神经递质或神经调质。由于这种肽的非成瘾性阿片类镇痛活性，它可能在疼痛管理中具有巨大的潜力。制备了负载Leu-Enk的N-三甲基壳聚糖（TMC）纳米粒，并作为经鼻途径的脑递送载体进行了评价。合成了TMC生物聚合物，并通过H-1 NMR谱进行了分析。采用离子凝胶法制备了TMC纳米粒子。平均肽包封效率和负载能力分别为78.28 +/- 3.8%和14 +/-1.3%。对于优化的制剂，发现平均粒度、多分散指数和zeta电位分别为443 +/- 23 nm、0.317 +/- 0.17和+15 +/- 2 mV。从纳米颗粒释放的Leu-Enk通过猪鼻粘膜的表观渗透系数（P-app）测定为7.45 +/- 0.30 x 10（-6）cm/s（-1）。与Leu-Enk溶液相比，从纳米颗粒释放的Leu-Enk对鼻粘膜的渗透性提高了35倍。小鼠脑切片的荧光显微镜检查显示，当通过TMC纳米颗粒鼻内给药时，荧光标记物NBD-F标记的Leu-Enk的累积更高，而观察到标记物溶液的脑摄取较低。此外，脑摄取的增强导致所观察到的Leu-Enk的抗伤害感受作用的显著改善，如通过热板和乙酸诱导的扭体试验所证明的。(C)2013爱思唯尔有限公司版权所有。
Leucine-enkephalin (Leu-Enk) is a neurotransmitter or neuromodulator in pain transmission. Due to non-addictive opioid analgesic activity of this peptide, it might have great potential in pain management. Leu-Enk loaded N-trimethyl chitosan (TMC) nanoparticles were prepared and evaluated as a brain delivery vehicle via nasal route. TMC biopolymer was synthesized and analyzed by H-1 NMR spectroscopy. TMC nanoparticles were prepared by ionic gelation method. Mean peptide encapsulation efficiency and loading capacity were 78.28 +/- 3.8% and 14 +/- 1.3%, respectively. Mean particle size, polydispersity index and zeta potential were found to be 443 +/- 23 nm, 0.317 +/- 0.17 and +15 +/- 2 mV respectively for optimized formulations. Apparent permeability coefficient (P-app) of Leu-Enk released from nanoparticles across the porcine nasal mucosa was determined to be 7.45 +/- 0.30 x 10(-6) cm s(-1). Permeability of Leu-Enk released from nanoparticles was 35 fold improved from the nasal mucosa as compared to Leu-Enk solution. Fluorescent microscopy of brain sections of mice showed higher accumulation of fluorescent marker NBD-F labelled Leu-Enk, when administered nasally by TMC nanoparticles, while low brain uptake of marker solution was observed. Furthermore, enhancement in brain uptake resulted into significant improvement in the observed antinociceptive effect of Leu-Enk as evidenced by hot plate and acetic acid induced writhing assay. (C) 2013 Elsevier B.V. All rights reserved.