Intranasal microemulsion for targeted nose to brain delivery in neurocysticercosis: Role of docosahexaenoic acid.
Intranasal microemulsion for targeted nose to brain delivery in neurocysticercosis: Role of docosahexaenoic acid.
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DOI：
10.1016/j.ejpb.2015.08.008
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发表时间：
2015-10
期刊：
影响因子：
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通讯作者：
Rajshree L. Shinde;G. Bharkad;P. Devarajan
中科院分区：
文献类型：
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作者：
Rajshree L. Shinde;G. Bharkad;P. Devarajan
报道了一种新型阿苯达唑亚砜(ABZ-SO)和姜黄素(Cur)的鼻腔微乳(MES)鼻内给药治疗脑囊虫病。用简单溶液法制备的MES颗粒大小为20 nm，Zeta电位为负，稳定性好。二十二碳六烯酸(DHA)微球显示药物通过绵羊鼻黏膜的透过率高，且速度快。与相同剂量的静脉注射DHA ME相比，鼻腔注射DHA ME可使脑内药物浓度升高10.76倍(ABZ-SO)和3.24倍(CUR)。两种药物的直接鼻到脑转运(DTP)均为95%。与Capmul ME和药物溶液(P<；)相比，DHA对大脑的高靶向效率(DTE)表明DHA在帮助鼻部到大脑递送方面的作用。组织病理学检查证实无明显变化。96小时碱性磷酸酶完全抑制和包囊崩解证实了ABZ-SO：CUR(100：10 ng/mL)DHA ME对猪带绦虫包囊的高效抑制作用。考虑到24小时的脑浓度分别为1400±160.1 ng/g(ABZ-SO)和120±35.2 ng/g(CUR)，药物浓度降低10倍时的体外疗效有力地支持了临床疗效的假设。DHA-ME鼻腔给药是一种很有前途的靶向鼻脑给药系统。
Intranasal Microemulsions (MEs) for nose to brain delivery of a novel combination of Albendazole sulfoxide (ABZ-SO) and Curcumin (CUR) for Neurocysticercosis (NCC), a brain infection are reported. MEs prepared by simple solution exhibited a globule size <20 nm, negative zeta potential and good stability. The docosahexaenoic acid (DHA) ME revealed high and rapid ex vivo permeation of drugs through sheep nasal mucosa. Intranasal DHA ME resulted in high brain concentrations and 10.76 (ABZ-SO) and 3.24 (CUR) fold enhancement in brain area-under-the-curve (AUC) compared to intravenous DHA MEs at the same dose. Direct nose to brain transport (DTP) of >95% was seen for both drugs. High drug targeting efficiency (DTE) to the brain compared to Capmul ME and drug solution (P< 0.05) suggested the role of DHA in aiding nose to brain delivery. Histopathology study confirmed no significant changes. High efficacy of ABZ-SO: CUR (100:10 ng/mL) DHA ME in vitro onTaenia soliumcysts was confirmed by complete ALP inhibition and disintegration of cysts at 96 h. Considering that the brain concentration at 24 h was 1400 ± 160.1 ng/g (ABZ-SO) and 120 ± 35.2 ng/g (CUR), the in vitro efficacy seen at a 10 fold lower concentration of the drugs strongly supports the assumption of clinical efficacy. The intranasal DHA ME is a promising delivery system for targeted nose to brain delivery.