納米類水滑石的可控制備、藥物傳遞及抗腫瘤性能
發(fā)布時(shí)間:2018-03-21 23:30
本文選題:類水滑石 切入點(diǎn):多孔支架 出處:《上海師范大學(xué)》2015年碩士論文 論文類型:學(xué)位論文
【摘要】:化療藥物甲氨蝶呤(MTX)在體內(nèi)不能夠長(zhǎng)時(shí)間維持有效藥物濃度,顯著降低了對(duì)骨腫瘤的治療效果。解決上述問題的有效途徑是構(gòu)建藥物傳遞系統(tǒng),使抗腫瘤藥物能夠在病灶部位進(jìn)行局部、持續(xù)、緩慢地釋放。類水滑石(LDHs)具有良好的生物相容性、低毒性和藥物傳遞性能,被廣泛地用于負(fù)載藥物。所以可以通過將MTX負(fù)載在類水滑石上,作為另一種治療骨肉瘤的方法。本文通過共沉淀法合成碳酸根型鎂鋁類水滑石(LDHs-C),通過焙燒還原法插入不同功能性陰離子,分別制備了硝酸根型、硅酸根型和磷酸根型鎂鋁類水滑石(LDHs-N、LDH-Si和LDH-P),借助SEM、TEM、XRD、FTIR、BET與ICP等分析手段表征類水滑石的表面形貌與物相結(jié)構(gòu)。四種類水滑石為層狀結(jié)構(gòu),具有六方片狀形貌,具有較大的比表面積(LDHs-C為107.407 m2/g,LDHs-N為205.22m2/g、LDH-Si為153.538 m2/g和LDH-P為34.634 m2/g),由于類水滑石納米片之間堆積產(chǎn)生了介孔結(jié)構(gòu)。不同的層間陰離子對(duì)類水滑石的穩(wěn)定性有一定影響,穩(wěn)定性順序?yàn)長(zhǎng)DH-SiLDH-PLDH-CLDH-N。不同類水滑石在去離子水中具有不同溶解度,可釋放出Mg2+和所對(duì)應(yīng)的陰離子。采用人骨髓間充質(zhì)干細(xì)胞(h BMSCs)體外培養(yǎng)實(shí)驗(yàn)初步探索了四種類水滑石的生物相容性能和骨誘導(dǎo)性;通過測(cè)定樣品中MTX的濃度,確定四種類水滑石的藥物負(fù)載和釋放性能;通過觀察人骨肉瘤細(xì)胞Saos-2接種于負(fù)載不同量MTX的LDHs上的生長(zhǎng)情況,探索四種類水滑石的抗骨肉瘤能力。四種類水滑石均為生物安全材料,表現(xiàn)出了良好的生物相容性,優(yōu)于Hap的MTX藥物負(fù)載率、藥物緩釋效果和抗骨肉瘤性能。LDHs-Si表現(xiàn)出了較好的骨誘導(dǎo)能力可以促進(jìn)成骨基因的表達(dá)。為了研究類水滑石材料的臨床可行性,通過浸漬-提拉和水熱轉(zhuǎn)化法構(gòu)建了類水滑石/殼聚糖/碳纖維多孔支架(LDHs/CS/CFs),并通過SEM、TEM、XRD、FTIR、XPS與TG-DTA等分析手段對(duì)其進(jìn)行表征。合成LDHs/CS/CFs的最佳堿性條件為p H=10,此時(shí)多孔支架復(fù)合材料具有最佳的形貌,LDHs/CS在碳纖維氈上均勻涂覆,LDHs納米片在碳纖維氈上垂直生長(zhǎng)。通過浸泡SBF溶液,初步探索其體外活性,結(jié)果表明,構(gòu)建的LDHs/CS/CFs具有較好的體外活性,可以促進(jìn)片狀類骨型磷灰石的形成。采用人骨髓間充質(zhì)干細(xì)胞(h BMSCs)體外培養(yǎng)實(shí)驗(yàn)初步探索了其生物相容性能,表明LDHs/CS/CFs具有較好的生物相容性,h BMSCs細(xì)胞在其表面具有較強(qiáng)的生長(zhǎng)能力與良好的鋪展性。
[Abstract]:The chemotherapeutic drug methotrexate (MTX) can not maintain the effective drug concentration for a long time in vivo, which significantly reduces the therapeutic effect on bone tumor. The effective way to solve the above problem is to construct a drug delivery system. So that antitumor drugs can be locally, continuously, slowly released at the site of the lesion. The hydrotalcite-like LDHs have good biocompatibility, low toxicity and drug delivery. Is widely used to load drugs. So you can load MTX on hydrotalcite-like rocks, As another method of treatment for osteosarcoma, LDHs-Con was synthesized by coprecipitation method. Different functional anions were inserted into the hydroxides by roasting reduction method, and nitrate type was prepared respectively. The surface morphology and phase structure of hydrotalcite-like hydrotalcite are characterized by SEMTEMT-XRDX FTIRBET and ICP. The four kinds of hydrotalcite are layered and have hexagonal flake morphology. LDHs-C = 107.407 m ~ (2) / g ~ (-1) LDHs-N = 205.22 m ~ 2 / g ~ (-1) LDH-Si = 153.538 m ~ (2 / g) and LDH-P = 34.634 m ~ (2 / g) 路g ~ (-1). Because of the accumulation of hydrotalcite-like nanocrystals, mesoporous structure was formed. Different interlayer anions have some influence on the stability of hydrotalcite. The order of stability is LDH-SiLDH-PLDH-CLDH-N.The different hydrotalcite have different solubility in deionized water. The biocompatibility and bone inductivity of four kinds of hydrotalcite were preliminarily investigated by using human bone marrow mesenchymal stem cells (hBMSCs) in vitro, and the concentration of MTX in the samples was determined. To determine the drug loading and release properties of four kinds of hydrotalcite, to observe the growth of human osteosarcoma cell line Saos-2 inoculated on LDHs loaded with different amount of MTX, To explore the ability of anti-osteosarcoma of four kinds of hydrotalcite. The four kinds of hydrotalcite are biosafety materials, which show good biocompatibility and are superior to the drug loading rate of MTX of Hap. In order to study the clinical feasibility of hydrotalcite-like materials, drug slow-release and anti-osteosarcoma .LDHs-Si showed good osteoinductive ability to promote the expression of osteogenic gene. The hydrotalcite / chitosan / carbon fiber porous scaffolds LDHs / CS / CFS / CFS / CFS were constructed by impregnation-Czochralski and hydrothermal transformation. The LDHs / CS / CFS / CFS were characterized by SEMTEMT-XRDX FTIR XPS and TG-DTA. The optimum basic conditions for the synthesis of LDHs/CS/CFs were pH10, and the porous scaffolds were obtained. The composite material has the best morphology and the LDHs / CS is evenly coated on the carbon fiber felt and grown vertically on the carbon fiber felt. By soaking the SBF solution, The results showed that the constructed LDHs/CS/CFs had good activity in vitro and could promote the formation of bone like apatite. The biocompatibility of the constructed LDHs/CS/CFs was preliminarily explored by using human bone marrow mesenchymal stem cells (BMSCs) in vitro culture. The results showed that LDHs/CS/CFs had good biocompatibility on the surface of BMSCs cells and had strong growth ability and good spreading ability.
【學(xué)位授予單位】:上海師范大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2015
【分類號(hào)】:TQ460.1;TB383.1
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