本文選題：pH敏感性水凝膠微球　切入點：溶脹性能　出處：《河北科技大學》2014年碩士論文

【摘要】：pH敏感水凝膠作為一種新型的藥物載體，在人體內可以自動感應pH值的變化而進行收縮或溶脹，實現(xiàn)定點釋藥和智能給藥。本課題使用懸浮聚合法和反相懸浮聚合法分別制備了兩種pH敏感性水凝膠微球，在制備研究中考察了單體、交聯(lián)劑、引發(fā)劑、分散劑、分散介質等因素對pH敏感性水凝膠微球成球性、粒徑分布及溶脹率的影響，確定了最佳制備配方。通過傅里葉變換紅外光譜儀對其進行分析，驗證了聚合反應的完成；通過光學顯微鏡和掃描電子顯微鏡對水凝膠微球進行外部形態(tài)和內部結構的觀察，表明制得的水凝膠微球粒徑為微米級，內部為具有空隙的三維網(wǎng)格結構。以牛血清白蛋白(BSA)為模型藥物，對兩種pH敏感性水凝膠微球進行載藥及體外釋放初步研究中，均表現(xiàn)了明顯的pH敏感性，在酸性條件下(pH1.2)BSA釋放量小于20%，而在弱酸性條件下(pH6.8)的條件下快速達到釋放平衡，完成體外釋放試驗時釋放達到90%以上。隨后選擇載藥量較大的P(AA-g-PEGMA)水凝膠微球進行胰島素的載藥及體外釋放研究，在酸性條件下(pH1.2)胰島素的釋放量小于20%，而在弱酸性條件下(pH6.8)的條件下胰島素快速達到釋放平衡，釋放量達到90%以上。采用Caco-2細胞對水凝膠微球進行了細胞毒性試驗，不同濃度的水凝膠微球與細胞共同培養(yǎng)，最終的細胞存活率均接近100%，表明水凝膠微球對Caco-2細胞沒有毒性；培養(yǎng)在Transwell板上的Caco-2單層細胞用于模擬小腸上皮細胞，胰島素在Caco-2單層細胞的滲透性試驗表明水凝膠微球促進了胰島素的吸收，結果表明水凝膠微球適于作為胰島素的口服藥物載體。在體內動物試驗中選用Wistar雄性大鼠建立糖尿病模型，通過對比研究口服胰島素水凝膠微球與皮下注射胰島素、口服胰島素溶液等，顯示胰島素水凝膠微球具有降血糖療效，其釋放出來的胰島素被小腸吸收，，最終發(fā)揮了降血糖療效。以上這些結果都表明水凝膠微球作為大分子蛋白類藥物的口服給藥載體，具有潛在的研究價值和應用前景。
[Abstract]:As a new drug carrier, pH sensitive hydrogel can automatically contract or dilate in human body with the change of pH value, so as to realize fixed-point drug release and intelligent drug delivery.In this paper, two kinds of pH sensitive hydrogel microspheres were prepared by suspension polymerization and inverse suspension polymerization respectively. The monomer, crosslinking agent, initiator and dispersant were investigated.The influence of dispersing medium on the spheroidization, particle size distribution and swelling rate of pH sensitive hydrogel microspheres was studied.The polymerization was verified by Fourier transform infrared spectroscopy (FTIR), and the external morphology and internal structure of hydrogel microspheres were observed by optical microscope and scanning electron microscope.The results show that the size of the hydrogel microspheres is in the order of micron and the interior is a three-dimensional mesh structure with voids.Using bovine serum albumin (BSA) as a model drug, two kinds of pH sensitive hydrogel microspheres were loaded and released in vitro.The release amount of BSA was less than 20 in acidic condition, but in weak acid condition, the release balance was reached rapidly, and the release reached 90% when the release test was completed in vitro.Subsequently, the drug loading and in vitro release of insulin were studied by using the hydrogel microspheres of PnAA-g-PEGMA-loaded, and the release amount of insulin was less than 20 at acidic condition, but at pH 6.8 under weak acid condition.The amount released was more than 90%.Caco-2 cells were used to test the cytotoxicity of hydrogel microspheres. The cell survival rate of hydrogel microspheres with different concentrations of hydrogel microspheres was close to 100, indicating that hydrogel microspheres were not toxic to Caco-2 cells.Caco-2 monolayers cultured on Transwell plates were used to mimic small intestinal epithelial cells. The permeability test of insulin in Caco-2 monolayer cells showed that hydrogel microspheres promoted insulin absorption.The results showed that hydrogel microspheres were suitable for oral drug delivery of insulin.In vivo animal experiment, Wistar male rats were selected to establish diabetic model. By comparing the oral insulin hydrogel microspheres with subcutaneous insulin injection, oral insulin solution and so on, the results showed that insulin hydrogel microspheres had hypoglycemic effect.Its release of insulin is absorbed by the small intestine, and ultimately played a hypoglycemic effect.These results suggest that hydrogel microspheres as oral delivery carriers of macromolecular protein drugs have potential research value and application prospect.
【學位授予單位】：河北科技大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R943

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