Yang Qian, Zhao Chuang, Zhao Jun, Ye Yong
Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, People's Republic of China.
Int J Nanomedicine. 2017 May 2;12:3463-3470. doi: 10.2147/IJN.S132510. eCollection 2017.
Cobra neurotoxin (CNT), a peptide isolated from snake venom of , shows central analgesic effects in our previous research. In order to help CNT pass through blood-brain barrier (BBB) and improve its central analgesic effects, a new kind of CNT nanocapsules were prepared by double emulsification with soybean lecithin and cholesterol as the shell, and pheophorbide as the photosensitizer added to make it photoresponsive. The analgesic effects were evaluated by hot plate test and acetic acid-induced writhing in mice. The CNT nanocapsules had an average particle size of 229.55 nm, zeta potential of -53.00 mV, encapsulation efficiency of 84.81% and drug loading of 2.98%, when the pheophorbide content was 1% of lecithin weight. Pheophorbide was mainly distributed in outer layer of the CNT nanocapsules and increased the release of the CNT nanocapsules after 650 nm illumination. The central analgesic effects were improved after intraperitoneal injection of CNT at 25 and 50 µg·kg under 650 nm irradiation for 30 min in the nasal cavity. Activation of pheophorbide by red light generated reactive oxygen species which opened the nanocapsules and BBB and helped the CNT enter the brain. This research provides a new drug delivery for treatment of central pain.
眼镜蛇神经毒素（CNT）是从眼镜蛇蛇毒中分离出的一种肽，在我们之前的研究中显示出中枢镇痛作用。为了帮助CNT穿过血脑屏障（BBB）并提高其中枢镇痛效果，制备了一种新型的CNT纳米胶囊，采用大豆卵磷脂和胆固醇作为外壳进行双乳化，并添加脱镁叶绿酸作为光敏剂使其具有光响应性。通过热板试验和醋酸诱导的小鼠扭体反应来评估镇痛效果。当脱镁叶绿酸含量为卵磷脂重量的1%时，CNT纳米胶囊的平均粒径为229.55 nm，ζ电位为-53.00 mV，包封率为84.81%，载药量为2.98%。脱镁叶绿酸主要分布在CNT纳米胶囊的外层，并在650 nm光照后增加了CNT纳米胶囊的释放。在鼻腔650 nm照射30分钟的情况下，腹腔注射25和50 μg·kg的CNT后，中枢镇痛效果得到改善。脱镁叶绿酸被红光激活产生活性氧，打开纳米胶囊和血脑屏障，帮助CNT进入大脑。本研究为中枢性疼痛的治疗提供了一种新的药物递送方式。
