本文選題：PLGA + 阿奇霉素�。� 參考：《天津醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:牙周炎是一種發(fā)病率高且常見的慢性病,對(duì)牙齒支持組織有著廣泛的影響,臨床表現(xiàn)為牙齦的炎癥和出血、牙周袋的形成、牙槽骨吸收,和牙齒的松動(dòng)、移位,是成年人失牙的主要原因。炎癥反應(yīng)是免疫細(xì)胞、免疫分子、炎癥介質(zhì)共同參與的結(jié)果。在牙周微生物和宿主的相互作用中,宿主的反應(yīng)決定了牙周炎的進(jìn)程。炎癥微環(huán)境是造成牙周組織喪失和再生困難的主要原因,尋找能夠調(diào)控牙周炎癥微環(huán)境的方法是牙周組織再生的關(guān)鍵。阿奇霉素作為臨床上治療牙周炎常用的大環(huán)內(nèi)酯類抗生素,對(duì)炎性細(xì)胞因子具有下調(diào)作用,對(duì)破骨細(xì)胞的成熟分化具有抑制作用,臨床上直接應(yīng)用于牙周炎治療的有效性已經(jīng)得到了充分的肯定,但是長(zhǎng)期使用易產(chǎn)生耐藥性,易發(fā)生不良反應(yīng);口腔環(huán)境的復(fù)雜性及其特殊的解剖結(jié)構(gòu),使局部用藥作用時(shí)間受限,有必要研發(fā)一種局部藥物緩釋體系促進(jìn)阿奇霉素在牙周炎治療中的應(yīng)用。聚乳酸羥基乙酸共聚物(PLGA)具有良好的生物相容性和生物可降解性,在藥物遞送系統(tǒng)和組織修復(fù)領(lǐng)域得到了深入研究。但由于PLGA表面具備疏水性,不易吸附黏膜,利用天然高分子材料絲素蛋白修飾載阿奇霉素PLGA微球,不僅可以改善表面親疏水性,增強(qiáng)對(duì)粘膜的親附力,也可中和PLGA降解的酸性產(chǎn)物,維持口腔正常生理PH值,同時(shí)使阿奇霉素緩慢釋放,從而達(dá)到治療牙周炎的目的。方法:1.制備載阿奇霉素PLGA微球并進(jìn)行體外釋藥性檢測(cè)采用乳液-溶劑揮發(fā)法制備載阿奇霉素的PLGA微球,通過掃描電鏡及透射電鏡觀察其表面形貌及結(jié)構(gòu),優(yōu)化實(shí)驗(yàn)條件,獲得合理的載藥量和包封率。2.聚(丙烯胺鹽酸鹽)(PAH)及絲素蛋白對(duì)載阿奇霉素PLGA微球的改性修飾并進(jìn)行體外釋藥性檢測(cè)以層層自組裝法將PAH及絲素蛋白沉積在載阿奇霉素PLGA微球表面,通過Zeta電位和微球表面形態(tài)變化證實(shí)殼層材料的成功沉積。計(jì)算殼層材料修飾后的載阿奇霉素PLGA微球的載藥量及包封率;繪制殼層材料修飾后的載阿奇霉素PLGA微球的體外累積釋藥曲線。結(jié)果:1.在掃描電子顯微鏡下可見,不同攪拌速度制備的微球表面形態(tài)、粒徑大小均存在顯著性差異。攪拌速度越快(8000rpm),微球粒徑越小,表面形態(tài)較光滑;攪拌速度越慢(800rpm)微球粒徑越大,表面形態(tài)較粗糙呈點(diǎn)狀凹坑樣。通過測(cè)定不同質(zhì)量比的載阿奇霉素PLGA微球的藥物釋放,發(fā)現(xiàn)初始釋藥階段呈明顯的“突釋”,后續(xù)的釋放過程比較平穩(wěn),隨著PLGA的降解,阿奇霉素可以持續(xù)緩慢釋放。2.在掃描電鏡下觀察經(jīng)修飾后的載阿奇霉素PLGA微球,可以發(fā)現(xiàn)微球表面被覆有殼層材料,微球周圍可見析出的絲絡(luò)樣修飾材料,經(jīng)Zeta電位檢測(cè)證實(shí)了PAH及絲素蛋白的成功沉積。通過測(cè)定修飾后載阿奇霉素的PLGA微球的藥物釋放,可以發(fā)現(xiàn)經(jīng)修飾后載藥微球中的阿奇霉素釋放量明顯減少,阿奇霉素釋放速率得到調(diào)控。結(jié)論:1、以PLGA為載體材料阿奇霉素為加載藥物的藥物緩釋體系的攪拌速率不同制備的載藥微球形態(tài)及性質(zhì)不同,可根據(jù)所需藥物緩釋體系進(jìn)行制備方式的設(shè)計(jì)。2、提高投藥比例,載藥微球的載藥量及包封率上升,當(dāng)投藥量達(dá)到峰值時(shí),包封率明顯下降。3、經(jīng)過聚(丙烯胺鹽酸鹽)及絲素的成功改性,載藥微球的藥物釋放速率可以被調(diào)控。4、本實(shí)驗(yàn)為阿奇霉素的緩慢釋放提供了體外研究證據(jù),從而為后續(xù)體內(nèi)實(shí)驗(yàn)奠定了基礎(chǔ)。
[Abstract]:Objective: Periodontitis is a chronic disease with high incidence and common, the teeth support has a broad impact, the clinical manifestations of gingival inflammation and bleeding, periodontal pocket formation, alveolar bone resorption, and teeth loosening, displacement, is a major cause of tooth loss in adults. The inflammatory reaction is immune cells and immune molecules and inflammatory mediators involved in the interaction. In periodontal microorganisms and the host, the host reaction determines the periodontitis process. The inflammatory microenvironment is mainly caused by the loss and difficult regeneration of periodontal tissues, find the method can control inflammation microenvironment is critical for periodontal tissue regeneration azithromycin. As the clinical treatment of periodontitis of macrolide antibiotics commonly used, with a reduced role of inflammatory cytokines, inhibits the differentiation of osteoclasts, directly applied to clinical periodontal The effectiveness of anti-inflammatory treatment has been fully confirmed, but the long-term use is easy to produce drug resistance, prone to adverse reactions; the complexity of oral environment and its special anatomical structure, so that the local drug action time is limited, it is necessary to develop a drug delivery system promotes the application of azithromycin in the treatment of periodontitis. PLGA the copolymer (PLGA) has good compatibility and biodegradability of the organisms, is being studied in the field of drug delivery systems and tissue repair. But with the hydrophobic PLGA surface, is not easy to absorb the mucosa, natural polymer modified silk fibroin microspheres containing azithromycin PLGA, can not only improve the surface hydrophobicity, enhancement of mucous membrane the attachment force can neutralize PLGA degradation of acidic products, maintain normal oral physiological pH, and the slow release to azithromycin. The treatment of periodontitis. Methods: 1. preparation containing azithromycin PLGA microspheres and PLGA microspheres in vitro release test preparation containing azithromycin by emulsion solvent evaporation method, observe the surface morphology and structure by scanning electron microscopy and transmission electron microscopy, optimizing the experimental conditions, reasonable loading and encapsulation rate of.2. poly (propylene amine hydrochloride) (PAH) and silk fibroin on PLGA microspheres containing azithromycin modification and drug release in vitro detection by layer self-assembly method and PAH silk fibroin deposited on the surface of PLGA microspheres containing azithromycin, the Zeta potential and the surface morphology of the microspheres confirmed the successful deposition changes of shell materials. Calculation of shell materials after modification the PLGA containing azithromycin microspheres loading and encapsulation rate; drawing shell materials of modified PLGA containing azithromycin microspheres in vitro cumulative drug release curve. Results: 1. in scanning electron microscopy Microscopically, different stirring speed, the surface morphology of microspheres prepared by particle size were significantly different. The faster stirring speed (8000rpm), the smaller particle size of microspheres, the surface morphology is smooth; the stirring speed is slower (800rpm) microspheres with larger particle size, surface morphology of coarse punctate pits. The release of PLGA microspheres containing azithromycin drug determination of different mass ratio, it is found that the initial release stage showed a burst release and subsequent release process is relatively stable, with the degradation of PLGA, azithromycin sustained release of.2. can be observed by modified PLGA microspheres containing azithromycin can be found under the scanning electron microscope, surface coated microspheres shell material, microspheres precipitated wire winding around like modified materials by Zeta potentiometric detection confirmed the successful deposition of PAH and silk fibroin. PLGA microspheres modified by determination of drug release carrier of azithromycin Can be found, azithromycin modified microspheres release in significantly reduced, the release rate of azithromycin control. Conclusion: 1. Using PLGA as carrier materials for drug delivery system of azithromycin drug loaded the stirring rate of different preparation of microspheres morphology and properties of different, according to the required drug delivery system the design of.2 preparation methods, improve the dosage proportion of microspheres loading and encapsulation rate increased when the dosage reached the peak, the encapsulation rate was significantly decreased after.3, poly (allylamine hydrochloride) and silk fibroin modified release rate can be regulated.4 drug loaded microspheres this experiment provides evidence for the slow release of azithromycin in vitro, which lays the foundation for the subsequent in vivo experiments.

【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R781.4

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