本文選題：兩性霉素B　切入點：磁性脂質(zhì)體　出處：《河北科技大學(xué)》2014年碩士論文

【摘要】：本課題將抗真菌藥物兩性霉素B(Amphotericin B，AmB)制成磁性脂質(zhì)體，旨在對病變部位施加磁場的作用下提高藥物濃度，增強(qiáng)磁靶向性，從而降低毒副作用，并對制備的兩性霉素B磁性脂質(zhì)體(AmB magnetic liposomes，AmB-MLPs)進(jìn)行體內(nèi)外考察。實驗采用薄膜分散加超聲的方法制備AmB-MLPs，以粒徑和包封率為考察指標(biāo)，由單因素考察法確定了最優(yōu)處方和工藝，并對其物理性能進(jìn)行表征；分別以AmB注射液、AmB-MLPs肺部不加磁場及AmB-MLPs肺部加磁場三種方式經(jīng)尾靜脈注射，對KM小鼠體內(nèi)的藥代動力學(xué)、組織分布及肺部靶向性進(jìn)行考察；用以上三種方式經(jīng)頸動脈注射，在腦部設(shè)置磁場，對AmB進(jìn)入SD大鼠腦組織提高腦靶向性進(jìn)行研究。制備的AmB-MLPs的平均粒徑為250±12nm，平均包封率為78.02±2.05%，室溫下飽和磁化強(qiáng)度為32.54memu·g-1，有良好的體外磁場響應(yīng)性；KM小鼠藥動學(xué)結(jié)果顯示：AmB-MLPs加磁場組比AmB注射液組消除半衰期t1/2β明顯延長，清除率CL降低，平均滯留時間MRT延長，，藥時曲線下面積AUCt顯著增大，說明AmB-MLPs在磁場作用下延長了在血液中的循環(huán)時間；AmB-MLPs對肝和脾有一定的被動靶向作用，而在肺部設(shè)置磁場時，增強(qiáng)了肺部的磁靶向作用；經(jīng)頸動脈注射給藥，可以在一定程度上提高腦組織的藥物濃度，而在腦部施加固定磁場，可以進(jìn)一步增強(qiáng)藥物在腦部的濃集；大鼠腦組織切片普魯士藍(lán)染色結(jié)果顯示，腦部加磁場組比不加磁場組可見藍(lán)染顆粒密度大，進(jìn)一步說明AmB-MLPs經(jīng)頸動脈注射在磁場作用下，可以進(jìn)入腦組織，增強(qiáng)了對腦部的磁靶向作用�？傊�，制備的AmB-MLPs在磁場作用下，可以增強(qiáng)磁靶向性，降低毒副作用。
[Abstract]:In this paper, magnetic liposomes were made from amphotericin amphotericin B(Amphotericin amphotericin. The aim of this study was to increase the concentration of the drug and enhance the magnetic targeting ability under the action of magnetic field on the lesion, so as to reduce the toxicity and side effects.Amphotericin B magnetic liposome Amb magnetic liposome AmB-MLPswas prepared in vitro and in vivo.AmB-MLPswere prepared by thin-film dispersion and ultrasonic method. The particle size and entrapment efficiency were taken as the test indexes. The optimum formulation and process were determined by single-factor method, and the physical properties of the AmB-MLPswere characterized.The pharmacokinetics, tissue distribution and lung targeting of km mice were investigated by injecting AmB injection AmB-MLPs into the lung without magnetic field and AmB-MLPs by the tail vein respectively, and the three methods were injected into the carotid artery by the above three methods, the pharmacokinetics, tissue distribution and lung targeting of km mice were studied.A magnetic field was set up in the brain to study the effect of AmB on brain targeting of SD rats.鍒跺鐨凙mB-MLPs鐨勫鉤鍧囩矑寰勪負(fù)250鹵12nm,騫沖潎鍖呭皝鐜囦負(fù)78.02鹵2.05%,瀹ゆ俯涓嬮ケ鍜岀鍖栧己搴︿負(fù)32.54memu路g-1,鏈夎壇濂界殑浣撳紓佸満鍝嶅簲鎬

本文編號：1704640