本文選題：10-羥基喜樹堿 + 聚乙二醇-聚丙交酯-乙交酯　； 參考：《吉林大學(xué)》2014年碩士論文

【摘要】：藥物制劑的傳遞可以通過使用藥物傳遞系統(tǒng)來改善，包括脂質(zhì)體，膠束和聚合物納米粒子。另外，考慮到安全性，這些藥物傳遞系統(tǒng)必須具備高的載藥量，并在病灶部位具有長(zhǎng)效循環(huán)和累積效果。相比于其它的載體系統(tǒng)，，聚合物納米粒子有很多優(yōu)點(diǎn)。其可控的藥物釋放行為，穩(wěn)定性以及較好的生物相容性。盡管其唯一的缺點(diǎn)是使用對(duì)組織有一定毒性的有機(jī)溶劑，但是價(jià)格便宜，制備過程簡(jiǎn)單可以用于大規(guī)模工業(yè)生產(chǎn)。用于可控的聚合物納米粒子中生物可降解性和生物兼容性良好的PLGA已經(jīng)被研究作為生物活性分子治療劑的傳遞載體。且已經(jīng)被廣泛應(yīng)用很多年，并通過美國食品藥品監(jiān)督管理局批準(zhǔn)用于人類疾病治療。 PEG由于其不帶電荷，親水和無免疫原性等特點(diǎn)，是一種作為納米粒子表面修飾的最佳材料，可以減少調(diào)理素作用。 PLGA-PEG納米粒子可以避免腎臟清除，以延長(zhǎng)其血漿半衰期。而且，這些長(zhǎng)效循環(huán)納米粒子通過增強(qiáng)的滲透和保留效應(yīng)（EPR）優(yōu)先地累積在腫瘤組織和炎癥部位。PEG的這種能力也依賴于一些參數(shù)，例如分子重量、密度、PEG鏈的構(gòu)象和靈活性。另外，PLGA的生物分散特性也受粒子大小，PEG損失率等條件的影響。與其他長(zhǎng)效循環(huán)系統(tǒng)相比，PEG納米粒子的主要優(yōu)勢(shì)在于它的殼穩(wěn)定性以及其控釋能力。 本文主旨是通過四種不同分子量比例的MPEG-PLGA包裹抗腫瘤藥物10-羥基喜樹堿（10-HCPT）形成納米藥物載體。并對(duì)其膠束載體進(jìn)行流體動(dòng)力學(xué)（DLS）、紅外（FITR）表征，對(duì)其載藥量、包封率進(jìn)行測(cè)定，體外藥物釋放情況和體外降解情況進(jìn)行研究，最后對(duì)其抗腫瘤效果也進(jìn)行了研究。初步觀察、分析在雙親性嵌段共聚物形成的納米藥物載體中，分子大小以及親水嵌段與疏水嵌段比例對(duì)以上性質(zhì)的影響。 我們首先成功合成了MEPG(5k)-PLGA(3k)、 MPEG(5k)-PLGA(9k)、MPEG(5k)-PLGA(11k)、MPEG(5k)-PLGA(16k)四種不同的嵌段共聚物，通過透析法成功裝載10-HCPT。其中，MPEG(5k)-PLGA(9k)形成膠束的載藥量最高，MPEG(5k)-PLGA(11k)次之。且各組具有均一的粒徑，良好的分散性。體外釋放行為中，MPEG-PLGA(5k/11k)為藥物釋放動(dòng)力學(xué)實(shí)驗(yàn)中最優(yōu)組。其第一階段的突釋最不明顯，直到36h總釋放量達(dá)到89.13％，而后持續(xù)釋放到第72h，最終藥物的釋放量為91.06％。在緩釋行為和累積釋放量上都是四組中最好的。另外在體外釋放過程中，親水嵌段MPEG的比例越大，PBS介質(zhì)中pH下降越多。而在此過程中，各分子量的納米藥物膠束載體的大小基本未發(fā)生明顯變化，只是在納米藥物載體表面出現(xiàn)了裂隙。在降解過程中MPEG(5k)-PLGA(16k)降解為小片段的速度應(yīng)該是最慢的，且MPEG的比例越小，材料降解的越慢。納米藥物載體在釋放過程中的質(zhì)量變化與其親水嵌段和疏水嵌段組成的比例不同有關(guān)。并且隨著MPEG比例的減少，這種質(zhì)量損失的速度在下降，且總的質(zhì)量損失量減小。四種載體的體外抗腫瘤效果也有差異，其中MPEG(5k)-PLGA(9k)形成的膠束表現(xiàn)出較強(qiáng)的腫瘤殺傷能力，MPEG(5k)-PLGA(11k)僅次之。
[Abstract]:Drug delivery can through the use of a drug delivery system to improve, including liposomes, polymer micelles and nanoparticles. In addition, taking into account the safety of the drug delivery system must have high drug loading, and has long cycle and cumulative effect on the focus. Compared to other vector systems, polymer nanoparticles have many advantages. The release behavior of the drug control, stability and good biocompatibility. Although its only drawback is the use of organic solvents have a certain toxicity to the organization, but the price is cheap, simple preparation process can be used for large-scale industrial production. For polymer nanoparticles in controllable biodegradability and good biological compatibility has been studied as a PLGA delivery of biologically active molecules. The treatment agent and has been widely used for many years, and by the U.S. Food and drug supervision and management It was approved for use in human disease treatment.
PEG due to its uncharged, hydrophilic and non immunogenic characteristics, is one of the best materials for the surface modification of the nanoparticles, can reduce opsonization. PLGA-PEG nanoparticles can prevent renal clearance, to prolong the half-life of plasma. Moreover, the long-acting circulation nanometer particles through enhanced permeability and retention effect (EPR) the ability of.PEG preferentially accumulated in tumor tissue and inflammatory sites also depends on some parameters, such as molecular weight, density, PEG chain conformation and flexibility. In addition, PLGA is also affected by the dispersion characteristics of biological particle size and influence conditions of PEG loss rate. Compared with other long-acting circulation system, the main advantage of PEG nanoparticles it is the shell stability and its controlled release ability.
The purpose of this paper is the antitumor drug 10- hydroxycamptothecin through four different molecular weight ratio of the MPEG-PLGA package (10-HCPT). The formation of nano drug carrier and fluid dynamics on the micelle carrier (DLS), infrared (FITR) characterization, the drug loading, encapsulation efficiency was determined to study the in vitro drug release and in vitro degradation, finally the anti-tumor effect was also studied. Preliminary observation, analysis of amphiphilic block copolymer nano drug carrier formation, molecular size and hydrophilic block ratio on properties of the above effects of block and hydrophobic.
鎴戜滑棣栧厛鎴愬姛鍚堟垚浜?jiǎn)MEPG(5k)-PLGA(3k), MPEG(5k)-PLGA(9k),MPEG(5k)-PLGA(11k),MPEG(5k)-PLGA(16k)鍥涚涓嶅悓鐨勫祵孌靛叡鑱氱墿,閫氳繃閫忔瀽娉曟垚鍔熻杞

本文編號(hào)：1760492