CN115119948A - 一种可控自组装淀粉纳米胶束及其制备方法与应用 - Google Patents
一种可控自组装淀粉纳米胶束及其制备方法与应用 Download PDFInfo
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- CN115119948A CN115119948A CN202210655665.0A CN202210655665A CN115119948A CN 115119948 A CN115119948 A CN 115119948A CN 202210655665 A CN202210655665 A CN 202210655665A CN 115119948 A CN115119948 A CN 115119948A
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- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
本发明公开了一种可控自组装淀粉纳米胶束及其制备方法与应用。该制备方法是将酸解或酶解淀粉加入DMSO溶液中加热至淀粉完全溶解;搅拌状态下,将磷酸钠加入淀粉溶液中;向反应体系加入辛烯基琥珀酸酐,进行酯化反应;反应结束后,使用无水乙醇沉淀淀粉,洗涤,干燥、粉碎过筛后,得到酯化改性淀粉;将酯化改性淀粉溶解在水中获得酯化改性淀粉溶液;将酯化改性淀粉溶液搅拌下调节pH,得酯化淀粉纳米胶束溶液,其粒径为100nm~200nm,该酯化淀粉纳米胶束对于疏水性功能因子具有良好的包埋作用,以姜黄素为例,胶束的包封率为29%~43%,载药量为35μg/mg~52μg/mg,胶束化过程耗时短,粒径均匀可控,性质稳定。
Description
技术领域
本发明涉及一种淀粉纳米胶束,特别是涉及一种可控自组装酯化淀粉纳米胶束及其制备方法与应用,是一种可控自组装辛烯基琥珀酸酐改性淀粉纳米胶束及其制备方法与负载功能性疏水客体的应用方法;属于纳米复合材料领域。
背景技术
随着纳米技术的发展,各种形式的纳米递送载体被用于递送疏水性功能客体。中国发明专利201810867543.1公开了一种姜黄素纳米微胶囊的制备方法,以酯化改性蜡质玉米淀粉为壁材,以姜黄素为芯材,以二聚甘油二油酸酯为乳化剂,通过均质处理获得负载姜黄素乳液,并通过喷雾干燥获得尺寸为30-40μm的淀粉微胶囊。但该技术所得淀粉微胶囊尺寸过大,不具备纳米载体独有的高吸收率和高生物利用率的特性,不利于姜黄素在体内的吸收利用;同时经过淀粉改性、乳化和喷雾干燥处理,制备工艺复杂,能耗高。
目前用于制备胶束的材料主要为人工合成聚合物,其缺陷是不可生物降解和潜在的免疫原性。相比之下,天然聚合物良好的生物相容性、无致敏性和无毒性使其成为理想的胶束制备材料。因此,基于天然聚合物的纳米胶束递送系统引起了人们极大的兴趣。
聚合物的双亲性是制备双亲型聚合物胶束的前提。淀粉作为一种绿色可再生的天然聚合物材料,因含有大量的活性羟基,可通过化学改性的方法引入疏水性基团赋予淀粉双亲的性质。经过疏水改性后的淀粉在水溶液中能够通过疏水作力、静电作用力作用下自组装形成具有亲水性外壳和疏水性内核的球形淀粉胶束。辛烯基琥珀酸酐改性淀粉自组装为胶束的前提是较高的取代度,常规的水相合成法即使经优化后取代度仍远小于自组装的最低取代度要求。制备高取代度辛烯基琥珀酸酐改性淀粉常用吡啶法,因吡啶不仅能作为淀粉和OSA的共同溶剂,还能作为催化剂促进酯化反应的进行(Gu Feng,etal.2015.Preparation of starch nanospheres through hydrophobic modificationfollowed by initial water dialysis.Carbohydrate Polymers[J],115:605-612)。但是吡啶的高毒性限制了酯化改性淀粉的应用;此外,通过吡啶法获得淀粉羧基完全质子化,导致制备的胶束缺少电荷,在溶液中容易聚集沉淀,且胶束的自组装过程难以精确控制。通过反溶剂或透析法制备获得淀粉纳米胶束耗时长,制备速度较慢,难以大规模生产。这些缺陷限制了辛烯基琥珀酸酐改性淀粉胶束的应用及大规模工业化制备。因此,提供新型淀粉改性技术和胶束制备技术是工业化应用辛烯基琥珀酸酐淀粉胶束亟待解决的技术难题。
发明内容
本发明目的在于提供一种安全环保的,能够快速合成并精确控制淀粉胶束的形成和粒径分布,淀粉纳米胶束粒径为100~200nm,同时胶束具有强负电性,能够长期稳定的在于溶液中可控自组装辛烯基琥珀酸酐改性淀粉纳米胶束的制备方法。
本发明另一目的在于提供有良好的负载能力,胶束的包封率达到29%~43%,载药量为达到35~52μg/mg(如疏水客体姜黄素)的可控自组装辛烯基琥珀酸酐改性淀粉纳米胶束负载功能性疏水客体的应用方法。
本发明目的通过如下技术方案实现:
1.一种可控自组装酯化淀粉纳米胶束的制备方法,其特征在于包括以下步骤:
步骤1:将酸解或酶解淀粉加入DMSO溶液中加热至淀粉完全溶解;
步骤2:搅拌状态下,将磷酸钠加入步骤1中得到的淀粉溶液中;
步骤3:向步骤2中的反应体系加入辛烯基琥珀酸酐,进行酯化反应;
步骤4:酯化反应结束后,使用无水乙醇沉淀淀粉,洗涤,干燥、粉碎过筛后,得到酯化改性淀粉;
步骤5:将酯化改性淀粉溶解在水中获得酯化改性淀粉溶液;
步骤6:空白淀粉胶束的自组装:将酯化改性淀粉溶液搅拌状态下调节pH为5.5~4.5,获得可控自组装酯化淀粉纳米胶束溶液。
2.根据权利要求1所述的可控自组装酯化淀粉纳米胶束的制备方法,其特征在于,步骤1中,所述的淀粉为普通玉米淀粉、蜡质玉米淀粉、木薯淀粉、马铃薯淀粉或小麦淀粉的一种;所述的酶解淀粉为经普鲁兰酶酶解制得的淀粉;经酸水解或普鲁兰酶脱支制备成短直链淀粉;酸解或酶解淀粉在DMSO溶液中的质量浓度为10%~20%。
3.根据权利要求1所述的可控自组装酯化淀粉纳米胶束的制备方法,其特征在于,按淀粉干基计,步骤2中磷酸钠与淀粉质量比例为1:1~1:5。
4.根据权利要求1所述的可控自组装酯化淀粉纳米胶束的制备方法,其特征在于,步骤3中,淀粉干基与辛烯基琥珀酸酐质量体积比1:1~1:5,其中质量单位为克,体积单位为毫升;酯化反应温度为45℃~85℃,反应时间为2h~8h。
5.根据权利要求1所述的可控自组装酯化淀粉纳米胶束的制备方法,其特征在于,步骤4中,所述的洗涤是用90-95%乙醇洗涤淀粉3~4次;步骤5中,所述的酯化改性淀粉溶液的浓度为1mg/L~20mg/mL。
6.一种可控自组装酯化淀粉纳米胶束,其特征在于其由权利要求1-5任一项所述的制备方法制得。
7.权利要求6所述的可控自组装酯化淀粉纳米胶束在负载功能性疏水客体的应用,其特征在于,将疏水性功能因子加入可控自组装酯化淀粉纳米胶束溶液中充分溶解;搅拌状态下,调节pH为5.5~4.5,离心除去未溶解部分,获得载疏水性功能因子的淀粉胶束溶液。
8.根据权利要求7所述的可控自组装酯化淀粉纳米胶束在负载功能性疏水客体的应用,其特征在于,所述的疏水性功能因子为姜黄素、β-胡萝卜素、芦丁或槲皮素。
9.根据权利要求7所述的可控自组装酯化淀粉纳米胶束在负载功能性疏水客体的应用,其特征在于,所述的疏水性功能因子与干基淀粉的质量比为1:50~1:10。
10.根据权利要求7所述的可控自组装酯化淀粉纳米胶束在负载功能性疏水客体的应用,其特征在于,所述的调节pH是通过加入盐酸溶液调节;盐酸溶液的浓度为0.2~0.8mol/L。所述的离心转速为3000-3500rpm,离心时间2-8min。
与现有技术相比,本发明具有以下特点:
(1)本发明在淀粉的制备过程中使用磷酸钠代替吡啶合成高取代度辛烯基琥珀酸酐改性淀粉,克服了现有技术普遍使用吡啶,带来的高毒性问题,并进而限制了酯化改性淀粉的应用。
(2)本发明通过质子化诱导技术快速形成淀粉纳米胶束,所得淀粉纳米胶束粒径为100~200nm,同时胶束具有强负电性,能够长期稳定的在于溶液中,克服了类似中国发明专利201810867543.1纳米微胶囊粒径达到30微米以上的大尺寸的问题。
(3)本发明通过疏水内核搭载疏水性客体、并因其亲水性外壳而具有较长的体内循环时间、较好的稳定性、修饰性较强且生物利用率高等优点;并能通过自组装过程自行形成胶束,制备工艺简单,能耗极低。
(4)本发明采用了质子化诱导技术,能够快速合成并精确控制淀粉胶束的形成和粒径分布,并具有良好的负载能力,以疏水客体姜黄素为例,胶束的包封率为29%~43%,载药量为35~52μg/mg。
(5)本发明的制备和胶束化方法操作简单,工艺稳定,有利于大规模工业化生产。
附图说明:
图1为辛烯基琥珀酸酐改性酸解淀粉的红外光谱图。NS:酸解24h蜡质玉米淀粉;NA:酸解24h普通玉米淀粉;A1:取代度0.52的辛烯基琥珀酸酐改性酸解24h木薯淀粉;A2:取代度0.63的辛烯基琥珀酸酐改性酸解24h马铃薯淀粉;A3:取代度0.76的辛烯基琥珀酸酐改性酸解24h小麦淀粉。
图2为取代度0.52的辛烯基琥珀酸酐改性酸解24h木薯淀粉空白胶束的粒径分布图。
图3为辛烯基琥珀酸酐改性酸解淀粉的1H NMR图谱。NS:酸解24h蜡质玉米淀粉;NA:酸解24h普通玉米淀粉;A1:取代度0.52的辛烯基琥珀酸酐改性酸解24h木薯淀粉;A2:取代度0.63的辛烯基琥珀酸酐改性酸解24h马铃薯淀粉;A3:取代度0.76的辛烯基琥珀酸酐改性酸解24h小麦淀粉。
图4为取代度0.76的辛烯基琥珀酸酐改性酸解24h小麦淀粉空白胶束的TEM图。
图5为取代度0.76的辛烯基琥珀酸酐改性酸解24h小麦淀粉载姜黄素胶束的TEM图。
图6为取代度0.52酸解24h马铃薯改性淀粉溶液在不同质子化程度下的外观变化,10%代表OSA淀粉的质子化程度为10%,20%-99%以此类推。
具体实施方式:
为更好地理解本发明,以下结合实施例和附图对本发明进行进一步说明,而不是限定本发明范围。
为实现本发明目的,本发明发现,磷酸钠作为一种常见的无机碱,不仅能够代替高毒性的吡啶用于制备高取代度酯化淀粉,且相比氢氧化钠、碳酸钠、三乙胺等无机或有机碱,具有碱性适中、反应效率高、易分离等优点,不仅能够活化淀粉上的羟基,促进亲电加成反应的进行;更重要的是,磷酸钠能够将羧基去质子化,从而使改性淀粉具有强负电性和高溶解性,不仅能够赋予淀粉胶束具有较强的稳定性,而且为自组装过程的精确控制提供基础。质子化诱导技术通过控制羧基的质子化程度精确控制胶束的自组装过程并调节胶束尺寸。相比反溶剂或透析法,质子化诱导技术制备淀粉胶束所需时间极短,所得胶束尺寸均匀,粒径可控,性质稳定。因此本发明中的DMSO-磷酸钠反应体系和质子化诱导技术为淀粉胶束的工业化应用提供了技术基础。
本发明实施例中有关测试方法说明如下:
淀粉红外图谱的测定方法:采用KBr压片法测定,取10mg淀粉与150mgKBr混合后研磨并压片,用红外图谱仪(型号:Nicolet IS50,美国Thermo)对薄片进行测定。
淀粉1H核磁图谱的测定方法:取3mg淀粉样品加入0.6mL氘代DMSO,充分溶解后用核磁共振仪(型号:AVANCE III HD 600MHz,德国布鲁克)进行测定,并通过峰面积计算改性淀粉的取代度。
胶束的透射电镜观察方法:将浓度1mg/mL的胶束溶液滴在150目碳支持膜上,干燥后采用透射电子显微镜(型号:JEM 2100F,日本岛津)进行观察。
粒径和电位的测定方法:将获得的空白胶束或负载姜黄素的胶束稀释为浓度1mg/mL的溶液,后使用纳米激光粒度仪器(型号:Malvern-2000,美国马尔文)进行粒径,电位和PDI的测定。
实施例1:酸解时间对酸解蜡质玉米淀粉分子量的影响
(1)使用95%的乙醇溶液将蜡质玉米淀粉溶液调浓度为20%(W/W)。
(2)搅拌状态下,加入11.3mL的盐酸,控制反应温度65℃,反应时间分别为1、3、6、12、24h。
(3)经过步骤(2)后,分别向不同反应时间的反应体系中加入1mol/L的碳酸钠溶液调节pH为7,10000rpm离心5min获得酸解淀粉。
(4)经步骤(3)获得的淀粉经水洗涤,过滤后,50℃干燥24h,粉碎、过100目筛后得到酸解短直链淀粉,其测试情况如表1所示。
表1酸解时间对酸解蜡质玉米淀粉分子量的影响
注:WM-1h:酸解蜡质玉米淀粉1小时,WM-3h:酸解蜡质玉米淀粉3小时,以此类推。
根据表1可知,酸解处理可以极大的降低淀粉的分子量。随着酸解时间的增加,淀粉的数均分子量,重均分子量和分散系数降低,说明酸解降低了蜡质玉米淀粉的分子量,有利于后期的辛烯基琥珀酸酐改性。
实施例2:普鲁兰酶解普通玉米淀粉制备酶解淀粉
(1)将普通玉米淀粉加入0.1mol/L,pH为4.6的乙酸缓冲溶液中,形成浓度为20%(W/W)淀粉乳。
(2)沸水浴充分糊化后降温并保持至58℃,搅拌状态下加入3mL普鲁兰酶(酶活1498npun/g),酶解24h后。趁热3500rpm离心,保留上清液。
(3)将步骤(2)中获得的上清液沸水加热30min灭酶后3500rpm离心保留上清液。
(4)将步骤(3)中获得的上清液中加入3倍体积的无水乙醇沉淀30min,10000rpm离心5min获得酶解淀粉,将淀粉水洗3次后,50℃下干燥24h,经粉碎、过100目筛后得到酶解短直链淀粉。
经测试,酶解淀粉的数均分子量为2092,重均分子量为3238,分散系数为1.55。
实施例3:辛烯基琥珀酸酐改性淀粉的制备
以木薯淀粉为原料,分别依照实施例1和实施例2中的方法对木薯淀粉进行酸解和酶解处理,获得酸解木薯淀粉和酶解木薯淀粉。
(1)分别称取1g酸解和酶解淀粉(干基)加入10mL的DMSO中,85℃加热使淀粉完全溶解。
(2)在搅拌状态下,向步骤(1)获得的淀粉溶液中加入磷酸钠和辛烯基琥珀酸酐,其中磷酸钠与淀粉质量比为1:1,淀粉(干基)与辛烯基琥珀酸酐的质量体积比为1:5(质量和体积的单位分别是克和毫升),85℃条件下反应8h。
(3)向步骤(2)中获得的反应体系中加入3倍体积的无水乙醇沉淀,10000rpm离心5min获得辛烯基琥珀酸酐改性淀粉。
(4)将步骤(3)中获得的淀粉经95%乙醇洗涤3~4次,50℃下干燥24h,经粉碎、过100目筛后得到辛烯基琥珀酸酐改性淀粉。
磷酸钠和辛烯基琥珀酸酐的添加量对改性酸解和酶解木薯淀粉取代度的影响如表2所示,淀粉的红外和1H NMR图谱见图1和图3。
表2
注:A1代表辛烯基琥珀酸酐改性酸解淀粉,E1代表辛烯基琥珀酸酐改性酶解淀粉。
图1中改性淀粉在2960cm-1、2860cm-1、1733cm-1、1577cm-1以及图3中从0.85-2ppm处的特征峰表明OSA基团成功的接枝到淀粉链上。经1H NMR图谱计算可知A1和E1的取代度分别为0.76和0.75,属于高取代度淀粉,且酯化改性酸解淀粉和酯化改性酶解淀粉的取代度接近。
实施例4:辛烯基琥珀酸酐改性淀粉的制备
以马铃薯淀粉为原料,分别依照实施例1和实施例2中的方法对马铃薯淀粉进行酸解和酶解处理,获得酸解马铃薯淀粉和酶解马铃薯淀粉。
(1)分别称取1g酸解和酶解淀粉(干基)加入10mL的DMSO中,85℃加热使淀粉完全溶解。
(2)在搅拌状态下,向(1)步骤获得的淀粉溶液中加入磷酸钠和辛烯基琥珀酸酐,其中磷酸钠:淀粉质量比为1:5,淀粉(干基)与辛烯基琥珀酸酐的质量体积比为1:1(质量和体积的单位分别是克和毫升),45℃条件下反应2h。
(3)向(2)步骤中获得的反应体系中加入3倍体积的无水乙醇沉淀,10000rpm离心5min获得辛烯基琥珀酸酐改性淀粉。
(4)将(3)步骤中获得的淀粉经95%乙醇洗涤3~4次,50℃下干燥24h,经粉碎、过100目筛后得到辛烯基琥珀酸酐改性淀粉。磷酸钠和辛烯基琥珀酸酐的添加量对改性酸解和酶解马铃薯淀粉取代度的影响如表3所示,淀粉的红外和1H NMR图谱见图1和图3。
表3
注:A2代表辛烯基琥珀酸酐改性酸解淀粉,E2代表辛烯基琥珀酸酐改性酶解淀粉
图1中改性淀粉在2960cm-1、2860cm-1、1733cm-1、1577cm-1以及图3中从0.85-2ppm处的特征峰表明OSA基团成功的接枝到淀粉链上。经1H NMR图谱计算可知A2和E2的取代度分别为0.52和0.51,属于高取代度淀粉,且酯化改性酸解淀粉和酯化改性酶解淀粉的取代度接近。图2为取代度0.52的辛烯基琥珀酸酐改性酸解24h木薯淀粉空白胶束的粒径分布图。从图2可见,本实施例所得取代度0.52的辛烯基琥珀酸酐改性酸解24h木薯淀粉空白胶束的粒径主要集中在100-300纳米。
实施例5:辛烯基琥珀酸酐改性淀粉的制备
以小麦淀粉为原料,分别依照实施例1和实施例2中的方法对小麦淀粉进行酸解和酶解处理,获得酸解小麦淀粉和酶解小麦淀粉。
(1)分别称取1g酸解和酶解淀粉(干基)加入10mL的DMSO中,85℃加热使淀粉完全溶解。
(2)在搅拌状态下,向(1)步骤获得的淀粉溶液中加入磷酸钠和辛烯基琥珀酸酐,其中磷酸钠:淀粉质量比为1:5,淀粉(干基)与辛烯基琥珀酸酐的质量体积比例为1:5(质量和体积的单位分别是克和毫升),85℃条件下反应8h。
(3)向(2)步骤中获得的反应体系中加入3倍体积的无水乙醇沉淀,10000rpm离心5min获得辛烯基琥珀酸酐改性淀粉。
(4)将(3)步骤中获得的淀粉经95%乙醇洗涤3~4次,50℃下干燥24h,经粉碎、过100目筛后得到辛烯基琥珀酸酐改性淀粉。磷酸钠和辛烯基琥珀酸酐的添加量对改性酸解和酶解小麦淀粉取代度的影响如表4所示,淀粉的红外和1H NMR图谱见图1和图3。
图1中改性淀粉在2960cm-1、2860cm-1、1733cm-1、1577cm-1以及图3中从0.85-2ppm处的特征峰表明OSA基团成功的接枝到淀粉链上。经1H NMR图谱计算可知A3和E3的取代度分别为0.63和0.61,属于高取代度淀粉,且酯化改性酸解淀粉和酯化改性酶解淀粉的取代度接近。
表4
注:A3代表辛烯基琥珀酸酐改性酸解淀粉,E3代表辛烯基琥珀酸酐改性酶解淀粉
实施例6:质子化诱导淀粉胶束的可控自组装
(1)将实施例4中获得的A2样品加入水中制备浓度为1mg/mL的改性淀粉溶液。
(2)在搅拌状态下,将0.1mol/L的盐酸缓慢滴加至(1)步骤中的淀粉溶液中,通过调节pH值控制淀粉的质子化程度,从而精准控制胶束的自组装过程。质子化程度诱导胶束自组装的粒径和电位变化如表5所示,所得淀粉胶束溶液的外观浊度见图6。
由表5可知,胶束的粒径和电位在质子化程度60%时发生突变,粒径从20.66nm增加至129.34nm,电位从-14.4mV增加值-36.3mV。图6中胶束溶液的外观由澄清透明变为含有乳光的均一溶液,可以判断淀粉已成功自组装为淀粉胶束,且质子化程度小于60%时淀粉无法自组装。浊度和粒径结果表明调节淀粉的质子化程度能够控制淀粉的自组装行为,电位结果表明自组装获得的胶束溶液性质稳定(电位绝对值大于30mV)。相比传统透析法(透析时间24小时及以上)制备淀粉纳米胶束工艺(Gu Feng,et al.2015.Preparation ofstarch nanospheres through hydrophobic modification followed by initial waterdialysis.Carbohydrate Polymers[J],115:605-612),本发明通过质子化诱导制备纳米淀粉胶束仅需2-5分钟,制备时间大大缩短,且避免了高毒性吡啶试剂的使用,工艺简单,无需使用透析设备,不产生透析废水,适合大规模工业化生产。
表5
实施例7:空白淀粉胶束的制备
(1)将实施例3中获得的改性木薯淀粉加入水中制备浓度为1mg/mL的改性淀粉溶液。
(2)在搅拌状态下,将0.1mol/L的盐酸缓慢滴加至(1)步骤中的淀粉溶液中,缓慢调节pH以获得空白淀粉胶束溶液。利用酸解和酶解木薯改性淀粉制得的空白淀粉胶束的粒径、电位和分散系数测试情况如表6所示,空白淀粉的胶束(A1样品)形貌见图4。
相比传统透析法和溶剂法(耗时约12-48h),质子化诱导法制备胶束耗时极短(耗时约5-10min)。图4的结果表明,经质子化诱导后,辛烯基琥珀酸酐改性淀粉在水中形成了表面光滑的球形胶束,说明胶束自组装成功。由表6可知,相比酸解改性淀粉,酶解改性淀粉经自组装形成的淀粉胶束粒径更小,电位更高,PDI更小,说明淀粉胶束粒径分布更加均匀,稳定性更强。
表6
注:A1代表辛烯基琥珀酸酐改性酸解淀粉,E1代表辛烯基琥珀酸酐改性酶解淀粉
实施例8:质子化诱导淀粉胶束粒径的精确控制
(1)将实施例3中获得的E1样品加入水中制备浓度为1mg/mL的改性淀粉溶液。
(2)在搅拌状态下,将0.1mol/L的盐酸缓慢滴加至(1)步骤中的淀粉溶液中,通过调节pH值控制淀粉的质子化程度,从而精准控制胶束的粒径大小。最终形成淀粉胶束的粒径和电位见表。
表7
由表7可知,胶束的粒径和电位在随着质子化程度的增加逐渐增大,质子化程度由60%增加至90%时,胶束的粒径由90nm增加至157nm,表明淀粉的质子化程度能够精确控制胶束的粒径大小。
实施例9:载姜黄素淀粉胶束的制备
(1)将实施例5中获得的改性小麦淀粉加入水中制备浓度为1mg/mL的改性淀粉溶液。
(2)搅拌状态下,将疏水性功能因子姜黄素加入步骤(1)获得的淀粉溶液中,姜黄素与改性淀粉的质量比为1:10(淀粉质量以干基计)。
(3)在搅拌状态下,将0.5mol/L的盐酸缓慢滴加至(2)步骤中的淀粉溶液中,缓慢调节pH以获得载姜黄素淀粉胶束。溶液的最终pH、胶束的包埋率和载药量见表8,负载姜黄素的胶束形貌见图5。
表8
注:A3代表辛烯基琥珀酸酐改性酸解淀粉,E3代表辛烯基琥珀酸酐改性酶解淀粉。
对比图4和图5,包埋姜黄素后胶束的粒径显著增加,说明姜黄素被成功的包埋在胶束核中。根据表8可知,酶解淀粉自组装胶束的包埋率和载药量大于酸解淀粉胶束。相比中国发明专利201810867543.1中制备获得的负载姜黄素纳米微胶囊,本专利制备获得的载姜黄素纳米淀粉胶束粒径为300nm,远小于淀粉微胶囊的尺寸(粒径30~40μm),具备纳米载体独有的高吸收率和高生物利用率的特性,更利于姜黄素在体内的吸收利用;且制备工艺简单,无需乳化、喷雾干燥处理,制备成本低。
Claims (10)
1.一种可控自组装酯化淀粉纳米胶束的制备方法,其特征在于包括以下步骤:
步骤1:将酸解或酶解淀粉加入DMSO溶液中加热至淀粉完全溶解;
步骤2:搅拌状态下,将磷酸钠加入步骤1中得到的淀粉溶液中;
步骤3:向步骤2中的反应体系加入辛烯基琥珀酸酐,进行酯化反应;
步骤4:酯化反应结束后,使用无水乙醇沉淀淀粉,洗涤,干燥、粉碎过筛后,得到酯化改性淀粉;
步骤5:将酯化改性淀粉溶解在水中获得酯化改性淀粉溶液;
步骤6:将酯化改性淀粉溶液搅拌状态下调节pH为5.5~4.5,获得可控自组装酯化淀粉纳米胶束溶液。
2.根据权利要求1所述的可控自组装酯化淀粉纳米胶束的制备方法,其特征在于,步骤1中,所述的淀粉为普通玉米淀粉、蜡质玉米淀粉、木薯淀粉、马铃薯淀粉或小麦淀粉的一种;所述的酶解淀粉为经普鲁兰酶酶解制得的淀粉;经酸水解或普鲁兰酶脱支制备成短直链淀粉;酸解或酶解淀粉在DMSO溶液中的质量浓度为10%~20%。
3.根据权利要求1所述的可控自组装酯化淀粉纳米胶束的制备方法,其特征在于,按淀粉干基计,步骤2中磷酸钠与淀粉质量比例为1:1~1:5。
4.根据权利要求1所述的可控自组装酯化淀粉纳米胶束的制备方法,其特征在于,步骤3中,淀粉干基与辛烯基琥珀酸酐质量体积比1:1~1:5,其中质量单位为克,体积单位为毫升;酯化反应温度为45℃~85℃,反应时间为2h~8h。
5.根据权利要求1所述的可控自组装酯化淀粉纳米胶束的制备方法,其特征在于,步骤4中,所述的洗涤是用90-95%乙醇洗涤淀粉3~4次;步骤5中,所述的酯化改性淀粉溶液的浓度为1mg/L~20mg/mL。
6.一种可控自组装酯化淀粉纳米胶束,其特征在于其由权利要求1-5任一项所述的制备方法制得。
7.权利要求6所述的可控自组装酯化淀粉纳米胶束在负载功能性疏水客体的应用,其特征在于,将疏水性功能因子加入可控自组装酯化淀粉纳米胶束溶液中充分溶解;搅拌状态下,调节pH为5.5~4.5,离心除去未溶解部分,获得载疏水性功能因子的淀粉胶束溶液。
8.根据权利要求7所述的可控自组装酯化淀粉纳米胶束在负载功能性疏水客体的应用,其特征在于,所述的疏水性功能因子为姜黄素、β-胡萝卜素、芦丁或槲皮素。
9.根据权利要求7所述的可控自组装酯化淀粉纳米胶束在负载功能性疏水客体的应用,其特征在于,所述的疏水性功能因子与干基淀粉的质量比为1:50~1:10。
10.根据权利要求7所述的可控自组装酯化淀粉纳米胶束在负载功能性疏水客体的应用,其特征在于,所述的调节pH是通过加入盐酸溶液调节;盐酸溶液的浓度为0.2~0.8mol/L。
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