自组装壳聚糖基纳米药用泡囊的研究
摘要
本文首次提出在醛与壳聚糖的反应体系中,加入相转移催化剂十二烷
基磺酸钠,获得双亲性 N,N-双十二烷基化壳聚糖材料。研究了壳聚糖的分
子量和反应条件如反应温度、反应时间、催化剂/醛用量比等因素对壳聚
糖的烷基化取代度的影响。同时还对 N,N- 双十二烷基化壳聚糖单分子膜
和 LB 膜的性质进行研究,并测得其单分子层厚为 1.74nm。
本文创新性地进行了 N,N-双十二烷基化壳聚糖自组装纳米药用泡囊
的制备研究,并成功获得含助成囊剂和不含助成囊剂的两种 N,N-双十二烷
基化壳聚糖自组装纳米药用泡囊。此外还研究了壳聚糖基材料的化学结
构、助成囊剂及制备条件对纳米药用泡囊自组装成型的影响。以维生素 B12
为模型药物、胰岛素为实用药物,对各种自组装泡囊的药物包埋率、泡囊
材料的载药量以及泡囊的药物释放行为进行比较研究。实验结果表明:
N,N-双十二烷基化壳聚糖可用于实用药物胰岛素自组装纳米泡囊的制备,
其包封率和载药量较高,持续释放时间较长。这些性质对胰岛素载药泡囊
的实际应用非常有利。
本文还研究了全酰化壳聚糖、N,N-二酰化壳聚糖和高取代度的 O-二酰
化壳聚糖的制备方法,并通过元素分析、红外光谱和核磁共振进行表征。
同时用热分析和 X 射线衍射等方法研究了上述三种酰化壳聚糖产物的性
质。本实验成功制备了 O-双十二酰化壳聚糖和 O-双十六酰化壳聚糖自组
装泡囊。并用模型药物维生素 B12研究泡囊的药物释放行为,考察了酰化壳
聚糖自组装泡囊的药物包封率和载药量。实验结果还表明 O-二酰化壳聚
糖自组装载药泡囊的药物释放行为基本符合二级药物释放。
In this paper the amphiphilic N, N-dilauryl chitosan has first been
prepared by the phase transfer catalysis. The effects of molecular weight of
chitosan and reaction conditions on the substitution degree of alkyl group have
been studied. The properties of LB film and monolayer of the products were
studied to order to find some fundamental data for making self-assembled
vesicles out of this kind of material. The thickness of N, N-dilauryl chitosan
monolayer was measured as 1.74 nm.
Two novel kinds of self-assembled nanovesicles have successfully been
prepared by using N, N-dilauryl chitosan with and without additives. The
effects of molecular weight of chitosan, additives and preparation conditions
such as pH value of buffer on making self-assembled vesicles have been
studied. Vitamine B12 as model drug and insulin as applicable drug were used
in our study. The experiments have been done to study the drug-encapsulation
efficiency, the drug-loaded content and drug release behavior of various
vesicles. The experimental results show that N, N-dilauryl chitosan
self-assembled vesicles can be applied for encapsulation of insulin for its
bigger drug-encapsulation efficiency and longer sustaining time of drug.
The products of full acylated chitosan, N-diacyl chitosan and O-diacyl
chitosan were prepared and characterized in this paper as well. XRD
measurements were made for above three products and chitosan to investigate
the crystallinity change caused by the acylation. DSC-TG measurements were
made to study their thermo behaviour as well. The O-dilauroyl and
O-dipalmitoyl chitosan self-assembled nanovesicles have successfully been
prepared in the study. The experimental results indicate that O-diacylatedl
chitosan self-assembled vesicles show two-order of drug release bahaviour
according to the Fick’s formula.
基磺酸钠,获得双亲性 N,N-双十二烷基化壳聚糖材料。研究了壳聚糖的分
子量和反应条件如反应温度、反应时间、催化剂/醛用量比等因素对壳聚
糖的烷基化取代度的影响。同时还对 N,N- 双十二烷基化壳聚糖单分子膜
和 LB 膜的性质进行研究,并测得其单分子层厚为 1.74nm。
本文创新性地进行了 N,N-双十二烷基化壳聚糖自组装纳米药用泡囊
的制备研究,并成功获得含助成囊剂和不含助成囊剂的两种 N,N-双十二烷
基化壳聚糖自组装纳米药用泡囊。此外还研究了壳聚糖基材料的化学结
构、助成囊剂及制备条件对纳米药用泡囊自组装成型的影响。以维生素 B12
为模型药物、胰岛素为实用药物,对各种自组装泡囊的药物包埋率、泡囊
材料的载药量以及泡囊的药物释放行为进行比较研究。实验结果表明:
N,N-双十二烷基化壳聚糖可用于实用药物胰岛素自组装纳米泡囊的制备,
其包封率和载药量较高,持续释放时间较长。这些性质对胰岛素载药泡囊
的实际应用非常有利。
本文还研究了全酰化壳聚糖、N,N-二酰化壳聚糖和高取代度的 O-二酰
化壳聚糖的制备方法,并通过元素分析、红外光谱和核磁共振进行表征。
同时用热分析和 X 射线衍射等方法研究了上述三种酰化壳聚糖产物的性
质。本实验成功制备了 O-双十二酰化壳聚糖和 O-双十六酰化壳聚糖自组
装泡囊。并用模型药物维生素 B12研究泡囊的药物释放行为,考察了酰化壳
聚糖自组装泡囊的药物包封率和载药量。实验结果还表明 O-二酰化壳聚
糖自组装载药泡囊的药物释放行为基本符合二级药物释放。
In this paper the amphiphilic N, N-dilauryl chitosan has first been
prepared by the phase transfer catalysis. The effects of molecular weight of
chitosan and reaction conditions on the substitution degree of alkyl group have
been studied. The properties of LB film and monolayer of the products were
studied to order to find some fundamental data for making self-assembled
vesicles out of this kind of material. The thickness of N, N-dilauryl chitosan
monolayer was measured as 1.74 nm.
Two novel kinds of self-assembled nanovesicles have successfully been
prepared by using N, N-dilauryl chitosan with and without additives. The
effects of molecular weight of chitosan, additives and preparation conditions
such as pH value of buffer on making self-assembled vesicles have been
studied. Vitamine B12 as model drug and insulin as applicable drug were used
in our study. The experiments have been done to study the drug-encapsulation
efficiency, the drug-loaded content and drug release behavior of various
vesicles. The experimental results show that N, N-dilauryl chitosan
self-assembled vesicles can be applied for encapsulation of insulin for its
bigger drug-encapsulation efficiency and longer sustaining time of drug.
The products of full acylated chitosan, N-diacyl chitosan and O-diacyl
chitosan were prepared and characterized in this paper as well. XRD
measurements were made for above three products and chitosan to investigate
the crystallinity change caused by the acylation. DSC-TG measurements were
made to study their thermo behaviour as well. The O-dilauroyl and
O-dipalmitoyl chitosan self-assembled nanovesicles have successfully been
prepared in the study. The experimental results indicate that O-diacylatedl
chitosan self-assembled vesicles show two-order of drug release bahaviour
according to the Fick’s formula.
引文
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