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首页> 外文会议>Annual Conference of the Chinese Society of Micro-Nano Technology >Pretreatment with Huperzine A-loaclecl poly(lactide-co-glycolide) nanoparticles protects against lethal effects of Soman-induceci in mice
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Pretreatment with Huperzine A-loaclecl poly(lactide-co-glycolide) nanoparticles protects against lethal effects of Soman-induceci in mice

机译：Huperzine A-LOACLECL Poly（丙交酯 - 共乙酰基）纳米颗粒预处理可防止小鼠索曼 - Induceci的致命作用

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Huperzine A (HupA), an alkaloid isolated from the Chinese club moss, is a reversible inhibitor of cholinesterases which cross the blood-brain barrier and show high specificity for acetylcholinesterase (AChE). However, HupA induces unwanted side effects in an effective dose against nerve agent poisoning. In the present study, HupA-loaded poly(lactide-co-glycolide) nanoparticles (HupA-PLGA-NP) were prepared using the O/W emulsion solvent evaporation method. The results of SEM demonstrated that HupA-PLGA-NP had an spherical shape and a smooth surface without pores. It's mean diameter and PDI were 208.5±3.6nm and 0.09±0.01 respectively. The Zeta potential was -35.3±1.8mV and the drug loading was 2.86±0.6%. In vitro drug release studies showed that HupA-PLGA-NP had a sustained-release behavior in phosphate buffer solution, The accumulated amount of HupA was about 72.1% at 48h with a low burst release within 30min. The LD_(50) values of HupA and HupA-PLGA-NP were 1.40 and 4.85mg/kg respectively, showing that the toxicity of HupA was reduced by 3.5 times. We evaluated the protective efficacy for different doses of HupA or HupA-PLGA-NP against 1.0×LD_(95) (143.0μg/kg) soman toxicity. The results confirmed that HupA (0.3~0.5mg/kg) or HupA-PLGA-NP (0.5 ~ 1.5mg/kg) could ensure animals survive. However, about 10% of the animals injected with HupA (0.8mg/kg) died, while no animals died when injected with HupA-PLGA-NP (1.5mg/kg). Aim to 100% survival rate, the effective protective time (12h) of HupA-PLGA-NP (0.5mg/kg,iv) against 1.0×LD_(95) soman toxicity in mice was significantly prolonged compared with that of HupA (4h). The study of AChE activity showed that whole-blood and supernatant of brain diluted by 80-fold and 10-fold respectively were optimum in this study. AChE inhibition after administration of HupA and HupA-PLGA-NP (0.5mg/kg,iv) was recorded and analyzed, The peak values of AChE inhibition in whole-blood and brain by HupA-PLGA-NP (17.6% and 21.8%) were lower than those by HupA (33.7% and 31.9%) and AChE inhibition time by HupA-PLGA-NP was longer than that by HupA. These data confirmed that HupA-PLGA-NP had less toxic and more longer time than HupA against 1.0×LD_(95) soman poisoning and warrant further development as a potent medical countermeasure against chemical warfare nerve agents (CWNAs) poisoning.
机译：Huperzine A（Hupa）是从中国俱乐部苔藓中分离的生物碱，是一种可逆抑制胆碱酶的胆碱酶，其越过血脑屏障，并为乙酰胆碱酯酶（ACHE）表示高特异性。然而，HUPA在抗神经剂中毒的有效剂量中诱导不必要的副作用。在本研究中，使用O / W乳液溶剂蒸发方法制备HUPA负载的聚（丙交酯 - 共乙酰胺）纳米颗粒（HuPA-PLGA-NP）。 SEM的结果证明Hupa-PLGA-NP具有球形形状和光滑的表面，无孔。它的平均直径和PDI分别为208.5±3.6nm和0.09±0.01。 Zeta电位为-35.3±1.8mV，药物载荷为2.86±0.6％。体外药物释放研究表明，Hupa-PLGA-NP在磷酸盐缓冲溶液中具有持续释放的行为，HuPa的累积量在48h的48小时内为约72.1％，在30min内爆发的低爆发释放。 HUPA和HuPa-PLGA-NP的LD_（50）值分别为1.40和4.85mg / kg，表明HUPA的毒性降低了3.5倍。我们评估了针对1.0×LD_（95）（143.0μg/ kg）索曼毒性为1.0×ld_（95）的不同剂量的Hupa或Hupa-plga-np的保护效果。结果证实，HUPA（0.3〜0.5mg / kg）或hupa-plga-np（0.5〜1.5mg / kg）可以确保动物存活。然而，约10％的动物注射了HUPA（0.8mg / kg）死亡，而在注射Hupa-PLGA-NP（1.5mg / kg）时没有动物死亡。目的是100％存活率，与Hupa（4h）相比，Hupa-PLGA-NP（0.5mg / kg，iv）的有效保护时间（12h）对小鼠的1.0×LD_（95）小鼠的毒性显着延长了。 ACHE活性的研究表明，在本研究中，分别在80倍和10倍稀释的脑中血液和上清液是最佳的。记录并分析施用HuPA和Hupa-PLGA-NP（0.5mg / kg，IV）后的疼痛抑制，Hupa-Plga-np患者疼痛抑制的峰值值（17.6％和21.8％）低于Hupa（33.7％和31.9％），Hupa-Plga-np的疼痛抑制时间比Hupa更长。这些数据证实，Hupa-PLGA-NP比Hupa对1.0×LD_（95）索曼中毒的毒性和更长的时间较小，并且需要进一步发展作为针对化学战神神经药物（CWNA）中毒的有效医疗对策。

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