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β-環(huán)糊精載藥納米纖維的制備及其緩釋行為研究

發(fā)布時(shí)間:2018-12-29 09:11
【摘要】:β-環(huán)糊精(β-CD),一種生物相容性極好的超分子材料,由于其特殊的幾何結(jié)構(gòu),具有親水的外圍和疏水的內(nèi)腔,可以與大多數(shù)尺寸合適的分子形成主客體包合結(jié)構(gòu),贏得了極大關(guān)注。β-環(huán)糊精能夠改善包合物的化學(xué)和物理性質(zhì),包括防止客體分子受到外界條件的破壞、提升溶解性以及提高客體分子穩(wěn)定性的特點(diǎn),為制備復(fù)合材料提供了良好的屬性,近年來被廣泛應(yīng)用于藥物輔料。本文以β-環(huán)糊精為添加物,以生物相容性良好的有機(jī)物作為基材,制得了三種復(fù)合載藥納米纖維,再對(duì)其性能和應(yīng)用進(jìn)行了研究,主要內(nèi)容如下:(1)采用玉米醇溶蛋白(Zein)與β-CD在乙酸體系中通過靜電紡絲得到Zein/β-CD復(fù)合納米材料。DSC表明,通過加入β-CD,Zein的玻璃化轉(zhuǎn)變溫度遷移到了更高的溫度。之后,抗真菌藥物灰黃霉素(GSV)與β-CD形成包合結(jié)構(gòu),從而加載到復(fù)合材料中,制成載藥納米纖維,其熱學(xué)性能隨著差示掃描量熱法(DSC)進(jìn)行了研究,結(jié)果證實(shí)了包合結(jié)構(gòu)的存在。紫外光譜分析表明,載藥納米纖維最終的累積釋藥百分率超過60%,并且前期(8 h-48 h)的藥物釋放行為有一定的緩釋效果。(2)為了提高基材醋酸纖維素(CA)的可紡性,通過在N,N-二甲基乙酰胺(DMAc)中加入β-環(huán)糊精(β-CD),成功制備了不同配比的CA/β-CD復(fù)合納米纖維。之后,抗真菌藥物灰黃霉素(GSV)加載到復(fù)合基材中,制成載藥納米膜,DSC結(jié)果表明,β-CD包合了藥物GSV,使其具有較高的熱穩(wěn)定性。紫外光譜分析表明,載藥納米纖維最終的累積釋藥百分率超過75%,包合結(jié)構(gòu)的存在使載藥納米纖維在藥物釋放的前期有有一定的緩釋效果。(3)生物相容性良好的聚乙烯醇-苯乙烯吡啶(PVA-SbQ)被用作基礎(chǔ)聚合物交聯(lián)劑,結(jié)合了β-環(huán)糊精(β-CD)通過靜電紡制備了納米復(fù)合材料。FTIR證實(shí)β-CD的存在。復(fù)合納米材料的形貌和平均纖維直徑也通過SEM進(jìn)行了分析。此外,TGA分析得知PVA-SbQ/β-CD復(fù)合納米纖維的熱學(xué)性能得到了改善。而且發(fā)現(xiàn)交聯(lián)后的復(fù)合納米材料具有明顯的高拉伸強(qiáng)度(TS)以及更大的斷裂伸長(zhǎng)率(EB)。最終,抗真菌藥物灰黃霉素(GSV)在水溶液中與β-CD形成包合結(jié)構(gòu),從而加載到復(fù)合納米纖維中。紫外光譜分析表明,載藥納米纖維最終的累積釋藥百分率超過90%,表現(xiàn)出一定的緩釋效果。
[Abstract]:尾-cyclodextrin (尾-CD),) is a supermolecular material with excellent biocompatibility. Because of its special geometric structure, 尾-cyclodextrin has hydrophilic periphery and hydrophobic inner cavity, which can form a host and guest inclusion structure with most molecules of suitable size. 尾 -cyclodextrin can improve the chemical and physical properties of inclusion compounds, including the characteristics of preventing guest molecules from being destroyed by external conditions, enhancing solubility and enhancing the stability of guest molecules. It provides good properties for the preparation of composite materials and has been widely used in pharmaceutical excipients in recent years. In this paper, three kinds of composite drug-loaded nanofibers were prepared by using 尾 -cyclodextrin as additive and organic compounds with good biocompatibility as substrate, and their properties and applications were studied. The main contents are as follows: (1) Zein/ 尾-CD composite nanomaterials were prepared by electrostatic spinning of Zein (Zein) and 尾-CD in acetic acid system. DSC showed that 尾-CD, was added to the composite nanomaterials. The glass transition temperature of Zein migrated to a higher temperature. After that, the antifungal drug Grysoflavin (GSV) and 尾-CD formed inclusion structure, and then loaded into the composite to make drug-loaded nanofibers. Its thermal properties were studied with differential scanning calorimetry (DSC). The results confirm the existence of inclusion structure. UV spectrum analysis shows that the final cumulative drug release percentage of drug-loaded nanofibers exceeds 60%. In order to improve the spinnability of cellulose acetate (CA), the drug release behavior in the early stage (8 h-48 h) was controlled. 尾 -cyclodextrin (尾 -cyclodextrin) was added into N-dimethylacetamide (DMAc) to prepare CA/ 尾-CD nanofibers with different ratios. After that, the antifungal drug, Grysoflavin (GSV), was loaded into the composite substrate to make the drug-loaded nano-film. The DSC results showed that 尾-CD encapsulated the drug GSV, and made it have higher thermal stability. UV spectrum analysis showed that the final cumulative drug release percentage of the drug-loaded nanofibers was more than 75%. Due to the existence of inclusion structure, the drug-loaded nanofibers have a slow release effect in the early stage of drug release. (3) Polyvinyl alcohol and styrene pyridine (PVA-SbQ), which has good biocompatibility, is used as the basic polymer crosslinking agent. Nanocomposites were prepared by electrospinning with 尾-cyclodextrin (尾-CD). The presence of 尾-CD was confirmed by FTIR. The morphology and average fiber diameter of the nanocomposites were also analyzed by SEM. In addition, TGA analysis showed that the thermal properties of PVA-SbQ/ 尾-CD nanofibers were improved. It was also found that the crosslinked composite nanocomposites had obvious high tensile strength (TS) and greater elongation at break (EB). Finally, the antifungal drug Grysoflavin (GSV) formed inclusion structure with 尾-CD in aqueous solution, and then loaded into composite nanofibers. UV spectrum analysis showed that the final cumulative drug release percentage of drug-loaded nanofibers exceeded 90%, showing a certain sustained release effect.
【學(xué)位授予單位】:江南大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:TQ342.8

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