自组装N，N-双十二烷基壳聚糖纳米药用泡囊的研究
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摘要
N-烷基化壳聚糖是一类重要的壳聚糖衍生物，它可改变壳聚糖的亲疏水性，因而在医药、化妆品、环保、纺织等众多领域都有应用价值。为提高N-烷基化壳聚糖的取代度，本文首次提出在醛与壳聚糖反应体系中，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，并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的性质进行研究。
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B_(12)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研究打下坚实的理论和实验基础。
Chitosan and its derivatives are characterized by their biocompatibility, biodegradability, and drug-absorption enhancement. Their unique chemical and biological properties make it an attractive biomaterial for a variety of pharmaceutical applications. Chitosan with two long side chains of N-alkyl group is an important amphiphilic material, which has potential application in tissue engineering and drug delivery system. In this paper the amphiphilic N,N-dilauryl chitosan has been prepared by the phase transfer catalysis. The effect of molecular weight of chitosan and reaction conditions such as reaction temperature, reaction time and phasetransfer catalyst/aldehyde ratio on the substitution degree of alkyl group has been studied. And the -A isotherms of the products were measured in order to find some fundamental data for making self-assembled vesicles out of this kind of material.
Two kinds of self-assembled nanovesicles have first been prepared by using N, N-dilauryl chitosan with and without additives. The effect of molecular weight of chitosan, additives and preparation conditions such as pH value of buffer on making self-assembled vesicles has 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 of vesicle material, 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. This property is very important for its practical application.
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B_(12)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研究打下坚实的理论和实验基础。
Chitosan and its derivatives are characterized by their biocompatibility, biodegradability, and drug-absorption enhancement. Their unique chemical and biological properties make it an attractive biomaterial for a variety of pharmaceutical applications. Chitosan with two long side chains of N-alkyl group is an important amphiphilic material, which has potential application in tissue engineering and drug delivery system. In this paper the amphiphilic N,N-dilauryl chitosan has been prepared by the phase transfer catalysis. The effect of molecular weight of chitosan and reaction conditions such as reaction temperature, reaction time and phasetransfer catalyst/aldehyde ratio on the substitution degree of alkyl group has been studied. And the -A isotherms of the products were measured in order to find some fundamental data for making self-assembled vesicles out of this kind of material.
Two kinds of self-assembled nanovesicles have first been prepared by using N, N-dilauryl chitosan with and without additives. The effect of molecular weight of chitosan, additives and preparation conditions such as pH value of buffer on making self-assembled vesicles has 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 of vesicle material, 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. This property is very important for its practical application.
引文
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[3] 严俊．甲壳素的化学和应用．化学通报[J]，1984，10：26-31．
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[13] Dodne V, Amin Khan M, Merwin J R. Effect of chitosan on epithelval permeability and structure, Int J Pharm [J] 1999,182(1): 21-32.
[14] Madihally S V, Matthew H. Porous chitosan scaffolds for tissue engineering. Biomaterials [J], 1999,20(]2): 1133-1142.
[15] Nishimura S I, Kai H, Shinada K, et al. Regioselective synthesis of sulfated polysaccharides: specific anti- HIV - 1 activity of novel chitin and sulfates. Carbohydrate Res [J], 1998, 306(3): 427-433.
[16] Kurita K, Kojima T, Nishyama Y, et al. Synthesis and some properties of nonnatual polysaccharides: branched chitin and chitosan. Macromolecules [7],2000,33(13): 4711-4716.
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