背景:基于纳米技术发展起来的纳米载体介导的磁性载药系统,在外加磁场作用下,能实现位点特异性靶向给药的目的,有利于提高病灶部位的局部药物浓度,从而进一步提高治疗效果,减少全身毒副作用.目的:研究磁性聚乳酸-羟基乙酸氧化酚砷纳米微粒的制备工艺,评价纳米粒子特性.设计:首先选择几个可能影响纳米微粒特性的因素进行了单因素实验,然后再根据实验结果,结合统计学中的正交设计,获得了最佳优化处方.单位:解放军第二军医大学长海医院特诊科.材料:实验于2005-01/2006-03在解放军第二军医大学药学院药剂教研室完成.实验用氧化酚砷购自美国Sigma公司,聚乳酸-羟基乙酸由山东医疗器械研究所提供,纳米级四氧化三铁购自美国Sigma公司,聚乙烯醇购自北京有机化工厂,二氯甲烷等其他试剂均为分析纯,购于上海国药集团化学试剂有限公司.方法:运用超声乳化-溶剂挥发法制备磁性聚乳酸-羟基乙酸氧化酚砷纳米微粒,通过透射电镜观察微粒形态,振动样品磁强计确证纳米微粒磁性的存在,激光粒径仪测定纳米粒的粒径大小和分布,高效液相法测定氧化酚砷的载药量及包封率,并计算氧化酚砷体外释放百分率.主要观察指标:磁性聚乳酸-羟基乙酸氧化酚砷纳米微粒的形态、粒径、载药量、包封率、磁性及体外释放情况.结果:①微粒包封率和载药量:实验制备的纳米粒平均包封率为34.2%;5批纳米粒载药量分别为3.06%,3.15%,3.18%,3.21%,3.41%,平均载药量为3.20%,批间差异较小,说明工艺稳定性、重现性好.②微粒形态:纳米微粒呈圆形,表面光滑,分布均匀,不粘连,磁性微球中可见非均匀分散的黑色不透光区,为四氧化三铁微粒.③微粒粒径:分布范围窄(140～500 nm),平均290 nm.④微粒磁性:在不断改变外加磁场的大小与方向的情况下,微粒具有不同的磁化强度,说明氧化酚砷聚乳酸纳米微粒具有一定的磁响应性.⑤体外释放实验:氧化酚砷经过最初的快速释放后,进入缓慢控释阶段,于第8天时达到最终基本稳定的平台期.结论:实验获得了较满意的磁性聚乳酸-羟基乙酸氧化酚砷纳米微粒制备工艺;该纳米微粒在外加磁场的情况下有较好磁靶向性的作用,同时具备良好药物缓释作用.
揹景:基于納米技術髮展起來的納米載體介導的磁性載藥繫統,在外加磁場作用下,能實現位點特異性靶嚮給藥的目的,有利于提高病竈部位的跼部藥物濃度,從而進一步提高治療效果,減少全身毒副作用.目的:研究磁性聚乳痠-羥基乙痠氧化酚砷納米微粒的製備工藝,評價納米粒子特性.設計:首先選擇幾箇可能影響納米微粒特性的因素進行瞭單因素實驗,然後再根據實驗結果,結閤統計學中的正交設計,穫得瞭最佳優化處方.單位:解放軍第二軍醫大學長海醫院特診科.材料:實驗于2005-01/2006-03在解放軍第二軍醫大學藥學院藥劑教研室完成.實驗用氧化酚砷購自美國Sigma公司,聚乳痠-羥基乙痠由山東醫療器械研究所提供,納米級四氧化三鐵購自美國Sigma公司,聚乙烯醇購自北京有機化工廠,二氯甲烷等其他試劑均為分析純,購于上海國藥集糰化學試劑有限公司.方法:運用超聲乳化-溶劑揮髮法製備磁性聚乳痠-羥基乙痠氧化酚砷納米微粒,通過透射電鏡觀察微粒形態,振動樣品磁彊計確證納米微粒磁性的存在,激光粒徑儀測定納米粒的粒徑大小和分佈,高效液相法測定氧化酚砷的載藥量及包封率,併計算氧化酚砷體外釋放百分率.主要觀察指標:磁性聚乳痠-羥基乙痠氧化酚砷納米微粒的形態、粒徑、載藥量、包封率、磁性及體外釋放情況.結果:①微粒包封率和載藥量:實驗製備的納米粒平均包封率為34.2%;5批納米粒載藥量分彆為3.06%,3.15%,3.18%,3.21%,3.41%,平均載藥量為3.20%,批間差異較小,說明工藝穩定性、重現性好.②微粒形態:納米微粒呈圓形,錶麵光滑,分佈均勻,不粘連,磁性微毬中可見非均勻分散的黑色不透光區,為四氧化三鐵微粒.③微粒粒徑:分佈範圍窄(140～500 nm),平均290 nm.④微粒磁性:在不斷改變外加磁場的大小與方嚮的情況下,微粒具有不同的磁化彊度,說明氧化酚砷聚乳痠納米微粒具有一定的磁響應性.⑤體外釋放實驗:氧化酚砷經過最初的快速釋放後,進入緩慢控釋階段,于第8天時達到最終基本穩定的平檯期.結論:實驗穫得瞭較滿意的磁性聚乳痠-羥基乙痠氧化酚砷納米微粒製備工藝;該納米微粒在外加磁場的情況下有較好磁靶嚮性的作用,同時具備良好藥物緩釋作用.
배경:기우납미기술발전기래적납미재체개도적자성재약계통,재외가자장작용하,능실현위점특이성파향급약적목적,유리우제고병조부위적국부약물농도,종이진일보제고치료효과,감소전신독부작용.목적:연구자성취유산-간기을산양화분신납미미립적제비공예,평개납미입자특성.설계:수선선택궤개가능영향납미미립특성적인소진행료단인소실험,연후재근거실험결과,결합통계학중적정교설계,획득료최가우화처방.단위:해방군제이군의대학장해의원특진과.재료:실험우2005-01/2006-03재해방군제이군의대학약학원약제교연실완성.실험용양화분신구자미국Sigma공사,취유산-간기을산유산동의료기계연구소제공,납미급사양화삼철구자미국Sigma공사,취을희순구자북경유궤화공엄,이록갑완등기타시제균위분석순,구우상해국약집단화학시제유한공사.방법:운용초성유화-용제휘발법제비자성취유산-간기을산양화분신납미미립,통과투사전경관찰미립형태,진동양품자강계학증납미미립자성적존재,격광립경의측정납미립적립경대소화분포,고효액상법측정양화분신적재약량급포봉솔,병계산양화분신체외석방백분솔.주요관찰지표:자성취유산-간기을산양화분신납미미립적형태、립경、재약량、포봉솔、자성급체외석방정황.결과:①미립포봉솔화재약량:실험제비적납미립평균포봉솔위34.2%;5비납미립재약량분별위3.06%,3.15%,3.18%,3.21%,3.41%,평균재약량위3.20%,비간차이교소,설명공예은정성、중현성호.②미립형태:납미미립정원형,표면광활,분포균균,불점련,자성미구중가견비균균분산적흑색불투광구,위사양화삼철미립.③미립립경:분포범위착(140～500 nm),평균290 nm.④미립자성:재불단개변외가자장적대소여방향적정황하,미립구유불동적자화강도,설명양화분신취유산납미미립구유일정적자향응성.⑤체외석방실험:양화분신경과최초적쾌속석방후,진입완만공석계단,우제8천시체도최종기본은정적평태기.결론:실험획득료교만의적자성취유산-간기을산양화분신납미미립제비공예;해납미미립재외가자장적정황하유교호자파향성적작용,동시구비량호약물완석작용.
BACKGROUND: With the development of nanotechnology, a new system for the delivery of drugs by magnetic nanovectors has been proposed. Within a magnetic field, the system can implement site-specific drug administration, thereby raising drug concentration at the lesion focus, elevate therapeutic effects, and reduce side effects.OBJECTIVE: To study the preparation of magnetic poly D, L-lactide-co-glycolic acid phenylarsine oxide nanoparticles (M-PLGA-PAO-NPs) and to evaluate characteristics of the prepared nanoparticles.DESIGN: Several factors influencing nanoparticle characteristics were selected for single-factor tests. Then, according to experimental results, and in conjunction with orthogonally designed statistics, the optimized prescription was obtained. SETTING: Department of Special Diagnosis, Changhai Hospital, Second Military Medical University of Chinese PLA.MATERIALS: The study was performed at the Department of Pharmaceutics, School of Pharmacy, Second Military Medical University of Chinese PLA from January 2005 to March 2006. The reagents used were as follows: phenylarsine oxide (Sigma, USA), poly D, L-lactic-co-glycolic acid (Shandong Medical Apparatus Institute, China), ferroso-ferric oxide (nanometer, Sigma, USA), polyvinyl alcohol (PVA1788, Beijing Organic Chemical Industry Plant, China). Methylene dichloride and other agents were all analytical grade and purchased from Shanghai Sinopharm Chemical Reagent Co., Ltd, China.METHODS: M-PLGA-PAO-NPs were prepared through an emulsion-evaporation process. Nanoparticle shape was observed by transmission electron microscopy. Magnetism was determined by a vibrating sample magnetometer. The size and diametral distribution of nanoparticles were determined by a laser particle size analyzer. The encapsulation ratio and drug loading of phenylarsine were measured by high performance liquid chromatography (HPLC). The percentage of phenylarsine oxide release in vitro was calculated [the percentage of phenylarsine oxide release in vitro =(total dose of phenylarsine oxide-residual dose of phenylarsine oxide)/ total dose of phenylarsine oxide].MAIN OUTCOME MEASURES: The shape, size, drug loading, encapsulation ratio and release in vitro of M-PLGA-PAO-NPs.RESULTS: The prepared nanoparticles had an average encapsulation ratio of 34.2%. Drug loading of 5 batches of nanoparticles was 3.06%, 3.15%, 3.18%, 3.21%, and 3.41%, respectively, with an average drug loading of 3.20%. Drug loading difference was small between batches, indicating good stability and reproducibility of the technology. M-PLGA-PAO-NPs were spherical, smooth, evenly distributed and non-adhesive. Ferrosoferric oxide microparticles, which exhibited unevenly dispersed black opacities, were found in the magnetic microparticles. Nanoparticles were in a narrow size range, with an average diameter of 290 nm (range 140-500 nm). When the magnitude and the direction of the outside magnetic field were changed, nanoparticles showed different intensities of magnetization. This indicated that M-PLGA-PAO-NPs had a certain magnetic response. The in vitro nanoparticle-release curve indicated that drug release was initially fast followed by a slow controlled release, and on day 8, it was basically stable.CONCLUSION:The experiment acquires a satisfactory technique for preparation of M-PLGA-PAO-NPs. The prepared M-PLGA-PAO-NPs were well targeted and exhibited slowly controlled drug release effects.
