本文選題：聚乳酸　切入點(diǎn)：熱致相分離　出處：《河北大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：載藥微球是一種新型藥物制劑,可以通過調(diào)節(jié)和控制藥物的釋放速率實(shí)現(xiàn)長(zhǎng)效緩釋。本文采用反相微乳液結(jié)合相分離的方法制備具有多孔結(jié)構(gòu)的微球,將其用作藥物載體,研究其載藥性能。本文主要分為兩部分:第一部分:采用反相微乳液結(jié)合相分離的方法制備具有多孔結(jié)構(gòu)的微球,探究了不同濃度、轉(zhuǎn)速、聚乳酸(PLLA)分子量、相分離溫度和溶劑對(duì)微球大小、結(jié)構(gòu)和形貌的影響,并探究了不同結(jié)構(gòu)的PLLA微球在藥物緩釋方面的應(yīng)用。通過掃描電子顯微鏡(SEM)和Nano Measurer粒度分析軟件對(duì)微球的形貌和粒徑大小進(jìn)行分析,結(jié)果顯示,通過控制不同的反應(yīng)條件可以制備出不同形貌和大小的PLLA多孔微球。二氧六環(huán)溶劑體系制備的D-PLLA微球表面是納米 珊瑚狀‖的結(jié)構(gòu),內(nèi)部有很多相分離產(chǎn)生的小孔(1-2μm)。由THF溶劑體系制備的T-PLLA微球具有納米纖維狀的結(jié)構(gòu)(50-500nm)。使用兩者的混合溶劑時(shí)微球的結(jié)構(gòu)介于 珊瑚狀‖和纖維狀之間。微球的細(xì)胞實(shí)驗(yàn)表明制備出的多孔微球具有良好的生物活性。微球的藥物緩釋實(shí)驗(yàn)顯示D-PLLA微球和T-PLLA微球的載藥量分別為7.2%和10.6%,體外緩釋平穩(wěn),8h時(shí)累計(jì)釋放量分別為41.2%和75.3%,是較好的藥物載體。相對(duì)而言,T-PLLA微球的載藥量相對(duì)較大,體外緩釋時(shí)存在一定突釋。第二部分:采用模擬體液(SBF)法,將第一部分制備的PLLA微球在1.5倍的SBF中浸泡不同時(shí)間,制備了聚乳酸/羥基磷灰石(PLLA/HA)復(fù)合微球,并對(duì)其進(jìn)行載藥實(shí)驗(yàn)。采用SEM表征了微球表面HA沉積層形貌、覆蓋程度及HA晶粒晶型及尺寸。透射電鏡(TEM)結(jié)果表明HA晶體呈薄片狀;透射電鏡能譜(TEM-EDS)測(cè)得HA層Ca/P原子比為1.40,接近真實(shí)比;TEM高分辨檢測(cè)到HA的(110)和(002)晶面。X射線衍射(XRD)檢測(cè)到HA層的(002),(211),(300)和(222)晶面處的特征衍射峰。FTIR圖譜顯示PLLA/HA復(fù)合微球既具有PLLA的特征吸收峰,同時(shí)也具有HA的特征吸收峰載藥實(shí)驗(yàn)表明D-PLLA/HA載藥微球的載藥量為6.1%,體外緩釋曲線較好,24h時(shí)累計(jì)釋放89.7%,是一種較好的藥物載體。T-PLLA/HA載藥微球的載藥量為8.1%,24h時(shí)累計(jì)釋放93.9%,存在一定的突釋。
[Abstract]:Drug-loaded microspheres are a new drug preparation, which can achieve long-term sustained release by regulating and controlling the drug release rate. In this paper, microspheres with porous structure were prepared by reverse microemulsion combined phase separation method and used as drug carriers. This paper mainly includes two parts: the first part: the microspheres with porous structure were prepared by reverse microemulsion combined phase separation method, and the molecular weight of PLLA was investigated at different concentration, rotational speed and polylactic acid (PLLA). Effects of phase separation temperature and solvent on the size, structure and morphology of microspheres, The application of PLLA microspheres with different structures in drug delivery was investigated. The morphology and particle size of PLLA microspheres were analyzed by scanning electron microscope (SEM) and Nano Measurer. PLLA porous microspheres with different morphology and size can be prepared by controlling different reaction conditions. The surface of D-PLLA microspheres prepared by dioxane solvent system is the structure of coral-like nanocrystalline. The T-PLLA microspheres prepared by THF solvent system have a nano-fibrous structure of 50-500 nm. The structure of the microspheres is between coral-like and fibrous when the mixed solvents of both are used. The structure of T-PLLA microspheres is between coral-like and fibrous. The structure of T-PLLA microspheres prepared by THF solvent system is between coral-like and fibrous, and the structure of T-PLLA microspheres is between coral-like and fibrous. Cell experiments showed that the porous microspheres had good bioactivity, and the drug release experiments showed that the drug loading of D-PLLA microspheres and T-PLLA microspheres were 7.2% and 10.6, respectively, and the accumulative release amounts of D-PLLA microspheres and T-PLLA microspheres were 41.2% and 10.6 respectively at 8 h of steady release in vitro. 75.3% is a good drug carrier. The drug load of T-PLLA microspheres is relatively large. In the second part, the PLLA microspheres prepared in the first part were soaked in 1.5 times of SBF for different time to prepare polylactic acid / hydroxyapatite / PLLA / HA composite microspheres. SEM was used to characterize the morphology of HA deposit layer on the surface of the microspheres, the coverage degree, the crystal structure and size of HA. The results of transmission electron microscopy (TEM) showed that the HA crystal was flaky. The Ca/P atomic ratio of HA layer measured by TEM energy dispersive electron microscopy (TEM) is 1.40, which is close to the real ratio. Tem high resolution detection of HA is 110) and the X ray diffraction (XRD)) of HA layer. X-ray diffraction (XRD) is used to detect the characteristic diffraction peak of PLLA/HA composite microsphere at the crystal plane of HA layer. Both have characteristic absorption peaks of PLLA, At the same time, the characteristic absorption peak drug loading experiment of HA also showed that D-PLLA / HA microspheres were loaded with 6.1and the accumulative release was 89.7at 24 hours after a better sustained release curve in vitro. It was a better drug carrier. T-PLLA-HA microspheres were loaded with 8.1and 24h cumulative release. 93.9, there is a certain sudden release.
【學(xué)位授予單位】：河北大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：O633.14;TQ460.4

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