CN110227167B - 壳聚糖接枝脂质纳米囊包载大黄素在抑制病原菌生物被膜中的用途 - Google Patents
壳聚糖接枝脂质纳米囊包载大黄素在抑制病原菌生物被膜中的用途 Download PDFInfo
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Abstract
本发明公开了大黄素纳米囊在抑制病原菌生物被膜药物中的用途,属于大黄素纳米囊新的医药用途领域。本发明首先制备了壳聚糖接枝脂质纳米囊包载大黄素,简称大黄素纳米囊,通过激光共聚焦显微镜观察,发现大黄素纳米囊对病原菌生物被膜形成有抑制作用。荧光定量PCR检测结果发现,壳聚糖接枝脂质体包载大黄素纳米囊对大肠杆菌的群体感应相关基因luxS、lasK及lasR的表达呈剂量依赖关系。因此,壳聚糖接枝脂质纳米囊包载大黄素对于抑制病原菌生物被膜的形成效果明确,能够应用于制备抑制或干预病原菌生物被膜的药物,本发明为大黄素纳米囊在临床的应用提供了一种新的应用领域。
Description
技术领域
本发明涉及大黄素纳米囊新的医药用途,具体的说是一种壳聚糖接枝脂质纳米囊包载大黄素在抑制病原菌生物被膜中的用途。
背景技术
细菌生物被膜是指附着于生命或无生命物体表面被细菌胞外大分子包裹的有组织的细菌群体,是大部分病原菌的生长方式[O'Toole G.A.,Kaplan H.B.,Kolter R.,Biofilm formation as microbial development,Annual Review of Microbiology,2000,54:49-79;Costerton J.W.,Lewandowski Z.,Caldwell D.E.,Korber D.R.,Lappin-Scott H.M.,Microbial biofilms,Annual Review of Microbiology,1995,49:711-745.]。研究证实,被膜内细菌对抗生素耐药性提高了1000倍以上,是反复感染的重要原因之一,并保护病原菌抵御宿主的免疫应答[Jesaitis AJ,Franklin MJ,Berglund D,et al,Compromised host defense on Pseudomonas aeruginosa biofilms:characterizationof neutrophil and biofilminteractions,J.Immunol,2003,171(8):4329-4339;Costerton JW,Stewart PS,Greenberg EP.Bacterial biofilms:a common cause ofpersistent infections,Science,1999,284:1318-1322.];临床上对病原菌感染的治疗仍以抗生素应用为主。但由此引发的细菌耐药性问题同样不能忽视。已经证明,细菌生物被膜的形成受微生物群体感应系统调控。因此,发明或发现新的群体感应抑制剂或生物被膜抑制剂对临床上控制病原菌反复感染、避免耐药菌产生具有重要临床和现实意义。
目前,群体感应抑制剂主要采用化学合成、植物中提取及可实现长效释放的载体制备。然而,无论是合成亦或天然抑制剂,其抑制效果、体内稳定性及生物安全性均有待进一步研究。
我国中草药资源十分丰富。中药应用于临床包括感染性疾病的治疗具有悠久历史。本课题组前期对中药大黄的抗炎症反应等作用研究多年。但中药成分复杂,作用机制呈现多靶点。而大黄素是中药大黄的主要有效单体,药理作用与大黄相似。大黄素抗菌作用已经明确。可以尝试作为群体感应抑制剂。但大黄素水溶性差,限制其临床应用。因此,本发明设计并制备了大黄素纳米囊,以提高大黄素水溶性及生物利用度,达到更广谱的抑制生物被膜形成的作用。
发明内容
针对上述问题,本发明目的在于一种壳聚糖接枝脂质纳米囊包载大黄素在抑制病原菌生物被膜中的用途。
为实现上述目的,本发明采用技术方案为:
一种壳聚糖接枝脂质纳米囊包载大黄素在抑制病原菌生物被膜中的用途,所述包载大黄素壳聚糖接枝脂质纳米囊(简称大黄素纳米囊)在作为抑制病原菌生物的被膜中的应用。
所述包载大黄素壳聚糖接枝脂质纳米囊为将大黄素、油相、表面活性剂和壳聚糖按质量比为1-100:100-200:50-85:100-200混合,采用相反转法制备获得包载大黄素壳聚糖接枝脂质纳米囊。
所述油相为中链甘油三酯(MCT);表面活性为聚乙二醇15羟硬脂酸酯(HS15)。
所述病原菌为大肠埃希菌(Escherich coli)、金黄色葡萄球菌(Staphylococcusaureus)、铜绿假单胞菌(Pseudomonas aeruginosa)、沙门氏菌(Salmonella)或单增李斯特菌(Listeria monocytogenes)。
本发明与现有技术相比,具有如下优点和效果:
1.本发明将水溶性差的大黄素进行处理得到大黄素纳米囊,进而显著提高大黄素水溶性,对临床上剂量控制、应用等提供了理论依据,并且大黄素纳米囊对生物被膜抑制作用显著。
2针对生物被膜难控制的现状,本发明应用大黄素纳米囊进行治疗可以避免病原菌抗生素耐药性的产生。降低了大黄素的临床使用浓度,减少药物毒性及副作用,扩大了大黄素的临床应用范围。
3.本发明产品的制备过程条件温和。对病原菌生物被膜的抑制作用方式简单、可操作性强。
4.本发明大黄素纳米囊制备过程为绿色无毒,壳聚糖接枝脂质体包载大黄素纳米囊制备工艺简便,安全性高、成本较低,可实现高通量大规模制备。
附图说明
图1为本发明是实施例提供的大黄素纳米囊电镜下形态及粒径分布图;
图2为本发明是实施例提供的大肠杆菌生物被膜经大黄素纳米囊处理后随时间变化的激光共聚焦显微镜图;
图3为本发明是实施例提供的亚MIC浓度的大黄素及大黄素纳米囊对生物被膜形成抑制作用差异图。
图4为本发明是实施例提供的不同浓度大黄素及大黄素纳米囊对生物被膜内细菌抑制作用差异。
图5为本发明是实施例提供的不同孵育时间内大黄素及大黄素纳米囊对生物被膜形成抑制作用差异。
图6为本发明是实施例提供的大黄素及大黄素纳米囊对大肠埃希氏菌群体感应相关基因的抑制作用考察。
具体实施方式
以下结合附图和实施例对本发明做进一步说明。
本发明首先制备了壳聚糖接枝脂质纳米囊包载大黄素,通过激光共聚焦显微镜观察,发现大黄素纳米囊对病原菌生物被膜形成有抑制作用。荧光定量PCR检测结果发现,壳聚糖接枝脂质体包载大黄素纳米囊对大肠杆菌的群体感应相关基因luxS、lasK及lasR的表达呈剂量依赖关系。因此,壳聚糖接枝脂质纳米囊包载大黄素对于抑制病原菌生物被膜的形成效果明确,能够应用于制备抑制或干预病原菌生物被膜的药物,本发明为大黄素纳米囊在临床的应用提供了一种新的应用领域。
实施例1
包载大黄素壳聚糖接枝脂质纳米囊的制备:
采用相反转法制备脂质纳米囊,精密称取1.000g中链甘油三脂(MCT),0.940g聚乙二醇15羟硬脂酸酯(HS15)表面活性剂,0.060g卵磷脂于50mL圆底烧瓶,加入转子后固定到已预热的磁力搅拌水浴锅中(60℃),搅拌混匀后加入3%的NaCl溶液3.000mL,持续搅拌并加热到90℃以后以每分钟4℃的速率降温到60℃,重复加热到90℃之后降温到60℃,再进行一次升温-降温过程,而后加入10.0mg大黄素,继续搅拌10min后,将圆底烧瓶转移到磁力搅拌器上并迅速加入至15.00mL(0℃)的壳聚糖溶液中分散,最后定容到20.00mL,即获得包载大黄素壳聚糖接枝脂质纳米囊(参见图1);同时以不添加药物作为空白基质组;并且以不添加壳聚糖和药物作为对比。而后对上述所得各产物进行测定(参见表1)。
表1壳聚糖接枝脂质纳米囊包载大黄素粒径及zata电位分布
LNC:空白脂质纳米囊
CS-LNC:壳聚糖接枝脂质纳米囊
LNC-Emodin:大黄素纳米囊
CS-LNC-Emodin:壳聚糖接枝脂质纳米囊包载大黄素
由表1可见包载药物对纳米囊整体粒径无显著影响。壳聚糖的接枝会显著增加纳米囊粒径。本实施例中壳聚糖接枝脂质纳米囊包载大黄素粒径约为75nm,并且由于壳聚糖的接枝,纳米囊表面为负电性。此类特点的纳米囊具备以下优点:①粒径小于100nm的纳米囊更易于被细胞吞噬而发挥作用;②菌体表面为正电荷,负电性的纳米囊更易于与菌体发生相互吸引引起相互作用。③壳聚糖本身具备的抑菌作用会增加纳米囊的抑菌效果。
实施例2
对上述获得包载大黄素壳聚糖接枝脂质纳米囊以及大黄素裸药进行最小抑菌浓度(MIC)的测定:
⑴按照被比稀释法,分别制备浓度为200、150、100、50、25、20、10、5、2.5、1.25、0.65、0.35、0.15、0μg/mL的大黄素纳米囊和大黄素裸药。与灭菌后冷却至55℃的LB琼脂培养基混合均匀。待培养基冷却后即制备得到不同药物浓度的固体平板培养基。
⑵用镊子夹取牛津杯放入制备好的平板培养基内,并在培养皿外延做好标记。吸取150μl上述浓度的大黄素纳米囊和大黄素裸药样品注入到相应的牛津杯内,同时以不添加壳聚糖和药物的空白纳米囊做为对照。
⑶将培养皿移入37℃培养箱培养。在接下来的6-12h内观察菌体的生长情况及抑菌效果。
经测定大黄素裸药和包载大黄素壳聚糖接枝脂质纳米囊的最小抑菌浓度(MIC)分别为10μg/mL和2.5μg/mL。空白纳米囊不具备抑菌效果,说明该纳米囊载体绿色、安全。同时,该结果直接说明大黄素纳米囊具备更强的抑菌效果,可见其在临床上的可以采用更低的用药量,降低耐药菌的出现。
实施例3
对上述获得包载大黄素壳聚糖接枝脂质纳米囊以及大黄素裸药进行抑制效果测定:
将过夜活化的大肠杆菌K12MG1655培养液(活化过程按照现有技术进行)按1:100的体积比例接种于放有盖玻片的六孔板中,同时分别加入亚MIC(1/2、1/4、1/8、1/16)浓度的大黄素裸药及包载大黄素壳聚糖接枝脂质纳米囊,37℃静置培养48h,采用TCP法测定大黄素裸药及大黄素纳米囊处理对生物被膜内细菌数量的影响进而反应对生物被膜的的抑制作用(参见图3)。
结果表明,大黄素裸药及大黄素纳米囊对生物被膜形成均具有抑制作用,但大黄素纳米囊抑制作用更强。其可见相对于大黄素裸药,大黄素纳米囊可以更显著的抑制病原菌生物被膜的形成,表现出更强的生物被膜抑制作用。
实施例4
对上述获得包载大黄素壳聚糖接枝脂质纳米囊以及大黄素裸药进行对生物膜内细菌的活率及作用48h内活率进行考察,进一步评价大黄素纳米囊及大黄素裸药对生物被膜的抑制作用以及抑制持效性:
抑制作用:
⑴将过夜活化的大肠杆菌K12MG1655培养液(活化过程按照现有技术进行)按1:100的体积比例接种于放有盖玻片的六孔板中,静置培养48h形成生物被膜。
⑵加入2MIC、4MIC和8MIC浓度的大黄素裸药及包载大黄素壳聚糖接枝脂质纳米囊,共孵育4h后取生物被膜内细菌,稀释涂平板法测定不同药物剂型对生物被膜内细菌活性的影响,并按下面公式计算抑制率。(参见图4)
持效性:分别选择2MIC浓度的大黄素裸药及大黄素纳米囊,加入形成的生物被膜中,分别孵育4h、8h、12h和24h,孵育结束,稀释涂平板法测定不同药物剂型对生物被膜内细菌活性的影响,计算抑制率。(参见图5)
由图4、图5可见,伴随大黄素浓度的增加,对生物被膜内细菌活性及对生物被膜的抑制作用并没有显著上升。分析原因,认为大黄素这种水不溶性药物的作用浓度是固定的,并不会随药物浓度的增加而增强作用效果。而大黄素纳米囊的作用效果呈现明显的浓度依赖性。表明大黄素纳米囊的使用显著增加了大黄素的溶解度,使得有更多的药物分子进入菌体内发挥作用,表现为随大黄素纳米囊浓度的增加,对生物被膜的抑制率也显著增加。
结果表明,大黄素纳米囊具备更强的杀菌效果,同时,由于纳米囊的缓释效果,纳米囊抑菌效果维持时间较裸药延长。其可见大黄素纳米囊不但可以在亚MIC浓度下抑制病原菌生物被膜的形成,同时增加药物浓度至几倍MIC浓度时,可以产生杀菌作用,直接减少了生物被膜的形成。
实施例5
对上述获得包载大黄素壳聚糖接枝脂质纳米囊以及大黄素裸药进行对大肠杆菌群体感应相关基因的表达测定:
同时通过荧光定量PCR方法进一步考察大黄素裸药及纳米囊对大肠杆菌群体感应相关基因的表达。
a.细菌总RNA提取(Trizol法)
(1)取约2-3mL菌液,4℃,10000rpm离心5min,弃上清,收集细胞。
(2)加入1mL Trizol试剂,注射器反复吹打破碎细胞,室温静置5min,使核酸蛋白复合物充分裂解,-70℃保存。
(3)加入200μL氯仿,剧烈震荡30s,室温静置10min。4℃,12000rpm离心15min,此时溶液分为三层,RNA位于上层的无色水相中,中间层为白色蛋白层,下层为红色的苯酚-氯仿有机层。
(4)轻轻吸取水相层400μL,转移至新的Eppendorf管中,加入等体积的异丙醇,轻轻颠倒混匀,室温静置10min,4℃,12000rpm离心10min,弃上清。
(5)加入75%乙醇充分洗涤沉淀,4℃,8000rpm离心5min,弃上清。
(6)将Eppendorf管小心的倒扣在洁净的滤纸上,使乙醇快速挥发后,加入适量的(20-50μL)DEPC水,冰上充分溶解RNA。
(7)提取的总RNA用Nano Photometer微量紫外分光光度计测定浓度和纯炖,A260/A280比值在1.8-2.0之间,视为纯度良好。
b.引物设计
根据NCBI的基因库中大肠杆菌的基因序列数据,利用BLAST功能进行引物设计与比对,引物序列见表2,以16sRNA基因作为内参基因。引物合成由大连宝生物公司完成。
表2壳聚糖接枝脂质纳米囊包载大黄素粒径及zata电位分布
c.反转录(合成cDNA)
反应条件:
42℃2min(或者室温5-30min)Hold 4℃
反转录反应条件:
37℃15min;85℃5s;Hold 4℃
d.Real Time PCR
反应条件:
预变性:95℃30s
PCR反应:95℃5s;60℃20s;Repeat 40cycles
融解:95℃15s;60℃1min;95℃15s
Bio-Rad CFX Manager软件分析实验结果。
由图6可见,在相同药物浓度下,与大黄素裸药组相比,经壳聚糖纳米囊组处理的大肠杆菌,其群体感应相关的luxS、lsrK及lsrR基因均显著下降,尤其是与群体感应信号分子AI-2合成直接相关的luxS基因,下降极显著,并呈现剂量依赖趋势。分析原因认为,相同作用时间内,大黄素纳米囊会携带更多的药物分子进入菌体内部发挥作用,引起群体感应相关基因的表达下降。而且,由于大黄素纳米囊的逐渐释放作用,使得大黄素纳米囊对菌体基因表达的抑制作用持续一段时间,表现出图6所示的结果。
Claims (2)
1.一种壳聚糖接枝脂质纳米囊包载大黄素在制备抑制病原菌生物被膜药物中的用途,其特征在于:所述包载大黄素壳聚糖接枝脂质纳米囊在作为抑制病原菌生物的被膜中的应用;
所述包载大黄素壳聚糖接枝脂质纳米囊为将大黄素、油相、表面活性剂和壳聚糖按质量比为1-100:100-200:50-85:100-200混合,采用相反转法制备获得包载大黄素壳聚糖接枝脂质纳米囊;
所述油相为中链甘油三酯(MCT);表面活性剂为聚乙二醇15羟硬脂酸酯(HS15)。
2.按权利要求1所述的用途,其特征在于:所述病原菌为大肠埃希菌(Escherich coli)、金黄色葡萄球菌(Staphylococcus aureus)、铜绿假单胞菌(Pseudomonas aeruginosa)、沙门氏菌(Salmonella)或单增李斯特菌(Listeria monocytogenes)。
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---|
The effect of emodin on Staphylococcus aureus strains in planktonic form and biofilm formation in vitro;Xin Yan et al.;《Arch Microbiol》;20170614(第199期);1267–1275 * |
肉桂醛脂质体及其壳聚糖修饰物的制备与抑菌性研究;成方圆;《工程科技Ⅰ辑》;20181216;B024-546 * |
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