本文關(guān)鍵詞：層層組裝膜負(fù)載緩釋抗生素和抗腫瘤雙藥物的研究　出處：《太原理工大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 層層組裝聚合物膜 雙藥物負(fù)載 抗生素 抗腫瘤藥物

【摘要】：近年來,隨著納米技術(shù)的快速發(fā)展,納米尺度藥物傳送載體因在醫(yī)學(xué)領(lǐng)域具有很高的應(yīng)用價值而成為了載藥納米材料方面的研究熱點之一,其中單藥物載體的研究已經(jīng)相對成熟,關(guān)于雙藥物及多藥物傳送體系的研究便受到了研究工作者廣泛的關(guān)注。層層組裝聚合物膜是運用層層組裝技術(shù),讓帶異種電荷的聚電解質(zhì)利用雙方間非共價弱作用力而交替沉積的一種納米多層膜。它制備條件溫和、操作簡易,而且可以把不同性質(zhì)、不同種類的藥物分子以不同的方式實現(xiàn)在膜上的負(fù)載,基于以上所述,本文旨在通過層層組裝技術(shù),以無毒、生物相容并可降解的聚電解質(zhì)作為膜的基元,制備出了兩組可以共同負(fù)載抗生素與抗腫瘤藥物的雙藥物緩釋層層組裝膜,本研究為新的雙藥物傳送體系提供了實驗依據(jù)。首先,制備了可以負(fù)載緩釋兩種正電荷藥物鹽酸萬古霉素(VAN)和鹽酸柔紅霉素的(DNR)的多層膜。以復(fù)合物聚天冬氨酸-鹽酸萬古霉素(PASP-VAN)與殼聚糖季銨鹽(HTCC)作為構(gòu)筑基元,運用層層組裝技術(shù),制備了聚合物復(fù)合物膜(PASP-VAN/HTCC)*10,完成了VAN的層層組裝負(fù)載,并通過改變PASP-VAN和HTCC的p H值,研究了構(gòu)膜基元的p H值對VAN負(fù)載量的影響,得到成膜最佳p H條件為(PASP-VAN_(4.0)/HTCC_(8.0))*10,緩釋實驗表明,層層組裝負(fù)載的VAN緩釋時間為1650min。然后以最佳p H條件的聚合物復(fù)合物膜(PASP-VAN_(4.0)/HTCC_(8.0))*10為基礎(chǔ),讓第二種藥物DNR以擴散的方式完成后負(fù)載,實現(xiàn)兩種正電荷藥物在同一層層組裝聚合物膜的共同負(fù)載,記作DNR-(PASP-VAN_(4.0)/HTCC_(8.0))*10。雙藥物體系體外釋放結(jié)果顯示:DNR與VAN的釋放時間分別為540min與720min;運用原子力顯微鏡(AFM)得知:未組裝膜的基底、單藥物的膜(PASP-VAN_(4.0)/HTCC_(8.0))*10、雙藥物的膜DNR-(PASP-VAN4.0/HTCC_(8.0))*10三者的膜表面粗糙度依次增加。其次,研究了阻隔層對藥物緩釋效果的影響。為了延緩抗腫瘤藥物DNR的釋放速率,將雙藥物體系與阻隔層相結(jié)合。先制備聚合物膜(PASP_(4.0)/HTCC_(8.0))*20,讓DNR以擴散的方式先進行負(fù)載,再分別采用噴涂層層組裝法與浸泡層層組裝法在該聚合物膜表面組裝阻隔層(PASP/PAH)*n(n表示周期數(shù)),最后讓VAN以復(fù)合物PASP-VAN的形式與HTCC層層組裝到膜中,從而實現(xiàn)DNR與VAN的共同負(fù)載。實驗比較分析了噴涂層層組裝與浸泡層層組裝兩種方式下,10T阻隔層的組裝效果,并進一步探討了噴涂層層組裝方式下阻隔層的周期數(shù)對DNR釋放效果的影響,結(jié)果表明:阻隔層可以延緩DNR的釋放速率,兩種方式下制備的10T阻隔層,阻隔效果相差不大,但噴涂組裝比浸泡層層組裝效率高;噴涂層層組裝方式下20T阻隔層與10T阻隔層分別使DNR的釋放時間延長2310min和420min;雙藥物釋放顯示:VAN與DNR的釋放時間分別持續(xù)1680min和2700min,通過調(diào)節(jié)阻隔層的周期數(shù)可以實現(xiàn)對藥物的控釋。最后,制備了可以負(fù)載異種電荷藥物頭孢曲松鈉(CTX)和DNR的膜雙藥物緩釋體系。先將陽離子型復(fù)合物(PAH-CTX)與透明質(zhì)酸鈉(HA)作為膜材料,利用兩者間的靜電作用層層組裝制備膜(HA_(4.0)/PAH-CTX7.5)*6,再在此膜的表面繼續(xù)層層組裝空白膜(PASP_(4.0)/PDDA)*20,將藥物DNR以浸泡的方式后負(fù)載于空白膜上,并噴涂20T阻隔層來減緩DNR的釋放速率。釋放實驗表明,CTX釋放時間為9h,DNR的釋放時間持續(xù)81h,抗生素CTX的快速釋放有助于及時殺滅細(xì)菌以防感染,DNR長效釋放有助于減少抗腫瘤藥物的服用次數(shù),進而減弱DNR的毒副作用。
[Abstract]:In recent years, with the rapid development of nanotechnology, nano scale drug delivery carrier because it has a high application value in the medical field and has become one of the hot research of drug loaded nano materials, the study of single drug carrier has been relatively mature, research on double drug and drug delivery system has been studied extensively attention is the use of the polymer film layer by layer by layer by layer technique, let the oppositely charged polyelectrolyte by non covalent weak interactions between the two sides of a nano multilayer film and deposition. It is mild preparation conditions, simple operation, and can have different properties, different types of drug molecules in different ways to achieve load at the film, based on the above, this paper aims to self-assembly technology, with non-toxic, biocompatible and biodegradable polymer electrolyte membrane as basic element, prepared Two groups of double drug release of antibiotics and anticancer drugs common load LbL assembly films, this study provides experimental basis for the dual drug delivery system. Firstly, the preparation can load two positive charge drug release of vancomycin hydrochloride (VAN) and daunorubicin hydrochloride (DNR) with composite multilayer film. Poly aspartic acid (PASP-VAN) and vancomycin hydrochloride chitosan quaternary ammonium salt (HTCC) used as building blocks, using layers of assembly technology, polymer composite membrane was prepared (PASP-VAN/HTCC) *10, completed the LBL VAN load, and by changing the PASP-VAN and HTCC P H, of the P configuration H membrane element values of the load effect on the VAN film P H, get the best conditions for (PASP-VAN_ (4) /HTCC_ (8)) *10 release experiment showed that the release time of layer by layer VAN load for 1650min. and then to the polymer composite film the best conditions (PA P H SP-VAN_ (4) /HTCC_ (8)) *10, completed second drugs DNR the way to spread after the load, two kinds of positive charge drugs loads at the same layer by layer of polymer film, denoted as DNR- (PASP-VAN_ (4) /HTCC_ (8)) *10. double drug release system objects the results showed that the release time DNR and VAN were 540min and 720min; the use of atomic force microscope (AFM) that the unassembled membrane substrate, single drug membrane (PASP-VAN_ (4) /HTCC_ (8)) *10, DNR- double membrane drugs (PASP-VAN4.0/HTCC_ (8)) *10 three film rough surface the degree of increase in turn. Secondly, study the influence of barrier layer drug release effect. In order to delay the release rate of antitumor drug DNR, the dual drug system and the combination of the first barrier layer. The preparation of polymer film (PASP_ (4) /HTCC_ (8)) *20, let DNR the way to spread the first load. Then use the spraying layer group Charging method and immersion method to assemble the barrier layer by layer assembly layer on the surface of the polymer membrane (PASP/PAH) *n (N cycle number), finally let VAN and HTCC in the form of complex PASP-VAN self-assembly into the membrane, so as to realize the common load of DNR and VAN. The comparative analysis of a spray assembly and soaking the assembly layers in two ways, assembling effect of 10T barrier layer, and further discusses the influence of spraying layer by layer, number of cycles of barrier layer under the release effect of DNR results showed that the release rate of barrier layer can delay DNR, two kinds of methods for preparation of 10T barrier layer, the barrier effect is similar, but the spray assembly the assembly of high efficiency than soaking; spraying layer by layer mode 20T barrier layer and 10T layer respectively. The release time of DNR prolonged 2310min and 420min; double drug release showed that the release time of VAN and DNR respectively for 1680min and 2700min, The number of cycles regulating barrier layer can be achieved on the drug release control. Finally, the preparation can load different charges of ceftriaxone sodium drug (CTX) and DNR double membrane drug delivery system. The cationic complexes (PAH-CTX) and sodium hyaluronate (HA) as a membrane material, layer by layer assembly system the film prepared by the electrostatic interaction between the two (HA_ (4) /PAH-CTX7.5) *6, then the surface of this film to the assembly of blank membrane (PASP_ (4) /PDDA) *20, the drug DNR to soak after loaded on the blank film, release rate and spraying 20T barrier to slow release experiment of DNR. CTX showed that the release time was 9h, the release time DNR 81h sustained, rapid release of antibiotic CTX helps to kill bacteria to prevent infection, have helped to reduce the frequency of use of antitumor drugs DNR and DNR long-acting release, reduced toxicity.

【學(xué)位授予單位】：太原理工大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：TQ460.1

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