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光響應羧甲基殼聚糖納米囊的制備及研究

發(fā)布時間:2018-03-29 01:34

  本文選題:羧甲基殼聚糖 切入點:鄰硝基芐基 出處:《武漢理工大學》2014年碩士論文


【摘要】:刺激響應性高分子化合物是指在一定條件下,通過其自身物理或者化學性質(zhì)的改變,對溫度、pH等外部刺激作出敏銳應答的物質(zhì)。與傳統(tǒng)的外部刺激相比,光刺激具有其獨特的優(yōu)勢,因為外加光的時間、位置和角度都可以進行精確的控制,這樣就可以實現(xiàn)對控釋體的可控刺激。本文以丁二酸酐作為連接臂,在羧甲基殼聚糖的氨基上接枝具有光響應性的鄰硝基苯甲醇,制得光響應羧甲基殼聚糖衍生物,然后進一步制得光響應性的空心納米囊。主要研究工作和結論如下: 一、制備具有光響應性的羧甲基殼聚糖衍生物,確定其結構,研究其相關性質(zhì)。 采用丁二酸酐開環(huán)與光響應性的鄰硝基苯甲醇反應生成中間產(chǎn)物,然后通過中間產(chǎn)物上的羧基與羧甲基殼聚糖上的氨基反應生成酰胺鍵得到兩親性羧甲基殼聚糖衍生物,采用紅外與核磁手段表征衍生物的結構,通過TLC、UV、HPLC等技術手段考察和確定中間產(chǎn)物和羧甲基殼聚糖衍生物的光響應性。 二、以光響應羧甲基殼聚糖衍生物為原料制備空心納米囊,確定其穩(wěn)定性、光響應性和pH敏感性。 (1)將制備的羧甲基殼聚糖衍生物均勻分散到體系中,經(jīng)調(diào)節(jié)pH和超聲制得空心納米囊,然后再戊二醛的輔助交聯(lián)下得到穩(wěn)定性較好的空心納米囊,透射電鏡圖顯示,光響應性空心納米囊及戊二醛輔助交聯(lián)后的空心納米囊都具有很明顯的空心結構,并且形態(tài)規(guī)整,分布均勻,粒徑比較均一。與戊二醛輔助交聯(lián)前的空心納米囊相比,輔助交聯(lián)后的空心納米囊的殼結構更加緊密。 (2)動態(tài)光散射結果表明,結構經(jīng)過戊二醛輔助交聯(lián)鎖定的空心納米囊比未交聯(lián)的空心納米囊具有更好的穩(wěn)定性,并且平均粒徑明顯變小,分散更加均勻。 (3)光響應性空心納米囊及戊二醛輔助交聯(lián)后的空心納米囊都具有較好的光響應性。戊二醛輔助交聯(lián)的空心納米囊在光刺激條件下,結構中的光響應基團斷裂,殼骨架中的交聯(lián)網(wǎng)絡結構被破壞,,粒徑變大,分布變寬;未交聯(lián)的空心納米囊在光刺激條件下,結構中的光響應基團斷裂,親疏水比例發(fā)生改變,導致疏水作用力的減弱,最終空心納米囊破裂。 (4)戊二醛輔助交聯(lián)的空心納米囊顯示出明顯的pH敏感性。pH值在較低范圍時,其粒徑較小,而pH值在較高范圍時,其粒徑較大,但當pH值超過一定范圍時,粒徑又有變小的趨勢;納米囊中光響應基團的含量對空心納米囊的pH敏感性影響不大,這是輔助交聯(lián)劑戊二醛用量相同的原因;當pH<3.0時,空心納米囊會沉淀出來,但能夠重新分散在合適pH值的溶液中。 三、考察以滅草松作為藥物模型的載藥納米囊的藥物釋放釋放情況,為該納米模型在納米藥物載體領域的發(fā)展提供理論依據(jù)。 (1)以所制備的空心納米囊為載體,以滅草松為藥物模型,采用原位包載,得到載藥空心納米囊。投藥量影響空心納米囊的載藥量與包封率:隨著投藥量的增大,載藥量也不斷增大;但當投藥量的增大時,包封率先增大后減小,在一個臨界點時達到最大。 (2)光刺激環(huán)境影響納米囊的藥物釋放:在光刺激條件下,藥物有較快的釋放,而在無光刺激條件下,藥物的釋放相對緩慢。納米囊的組成影響納米囊的藥物釋放:在暗環(huán)境中,三種載藥納米囊的藥物釋放趨勢相同,都沒有或是極少量藥物釋放出來;在光刺激條件下,載藥納米囊中光響應基團的取代度越低,藥物釋放的速率越快。
[Abstract]:Stimuli responsive polymers is that under certain conditions, through its own physical or chemical properties change of temperature, pH and other external stimuli sensitive response of the material. Compared with the traditional external stimulation, light stimulation has its unique advantages, because the external light time, position and angle can be accurately control, which can be controlled to release to stimulate the body. In this paper, two Ding anhydride as linker in carboxymethyl chitosan grafted with amino light response 2 nitrobenzyl alcohol of the prepared light response of carboxymethyl chitosan derivatives, and then prepared light responsive hollow nano cystic. The research work and conclusions are as follows:
First, the derivatives of carboxymethyl chitosan with light responsiveness are prepared, their structures are determined and their related properties are studied.
The Ding two anhydride ring opening reaction of o-nitrobenzoic methanol formation of intermediate products and the light response, then the two amphiphilic carboxymethyl chitosan derivatives obtained by reaction of carboxyl and amino amide bond of Carboxymethyl Chitosan on the intermediate product, structure, using IR and NMR methods for the characterization of derivatives by TLC, UV, HPLC other technical means to examine and determine the intermediate product and carboxymethyl chitosan derivatives of the light response.
Two, the hollow nanoscale was prepared by light response to carboxymethyl chitosan derivative as raw material, and its stability, light responsiveness and pH sensitivity were determined.
(1) the preparation of carboxymethyl chitosan derivatives were dispersed into the system, by adjusting the pH and ultrasound prepared hollow nanocapsules, auxiliary crosslinking and then glutaraldehyde under hollow nanocapsules better stability, TEM micrographs showed that the optical response of hollow nanocapsules hollow nanocapsules and amyl aldehyde two auxiliary crosslinking after having a hollow structure obviously, and regular shape, uniform distribution of particle size is uniform. Compared with the hollow nanocapsules before the auxiliary crosslinking glutaraldehyde, shell hollow nanocapsules assisted after crosslinking more closely.
(2) the dynamic light scattering results show that the hollow nanocapsules constructed by glutaraldehyde cross-linking and locking are more stable than the uncrosslinked hollow nanocapsules, and the average particle size is smaller and the dispersion is more uniform.
(3) the optical response of hollow nano cystic hollow nano capsule and glutaraldehyde crosslinked auxiliary has better light response. Glutaraldehyde cross-linked hollow nanocapsules in auxiliary light stimulation conditions, structure of the light response group fracture, cross-linked network structure shell is destroyed and the particle size distribution. Wide; non crosslinked hollow nanocapsules in light stimulation conditions, structure of the light response group fracture, hydrophobic ratio change, weaken the hydrophobic force, the final hollow nano capsule rupture.
(4) hollow nanocapsules glutaraldehyde auxiliary crosslinking showed pH sensitivity of.PH obvious value in the lower range, the smaller particle size, and the value of pH in the high range, its larger size, but when the pH value exceeds a certain range, the particle size decreases; nanocapsules in light the response group content on hollow nanocapsules was pH sensitivity, which is why the same auxiliary glutaraldehyde dosage; when pH is less than 3, the hollow nanocapsules will precipitate out of solution, but can be re dispersed in an appropriate pH value.
Three, we investigated the release and release of drug loaded nanocapsules, which provided a theoretical basis for the development of nanocapsules in the field of nanomedicine carriers.
(1) using hollow nanocapsules prepared as the carrier, with bentazone as drug model, obtained by in situ loading, drug loaded nano hollow capsule. The dosage of drug loading and entrapment efficiency of hollow nanocapsules: with the increase of drug dosage, drug loading is increasing constantly; but with the increase of investment the dosage, encapsulation first increases and then decreases, reaches the maximum at a critical point.
(2) light stimulation drug environmental impact nanocapsules release: in light stimulus conditions, drug fast release, but in the absence of light stimulation conditions, the drug release is relatively slow. Effects of nano capsule drug nanocapsules release: in the dark environment, the three kinds of drug loaded nano capsule release the same trend, have no or very little drug release; in light stimulus conditions, the degree of substitution groups lower light response of the drug loaded nano capsule, the rate of drug release more quickly.

【學位授予單位】:武漢理工大學
【學位級別】:碩士
【學位授予年份】:2014
【分類號】:R943

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