载异烟肼利福平聚乳酸纳米粒的制备及体外释药

背景:微载体药物因具有靶向性、控释性、稳定性、更好的安全性备受关注.目的:观察载异烟肼利福平两种抗结核药于同一聚乳酸纳米粒的给药系统及体外释放特性.方法:采用改良的自乳化二元溶剂扩散法制备载异烟肼和利福平纳米粒,亚微粒径分析仪测定纳米粒粒径及分布,透射电镜观察其形态;高效液相色谱仪建立测定异烟肼、利福平的载药量和包封率;以磷酸盐缓冲液为释放介质,观察载异烟肼和利福平纳米粒的体外释药特性.结果与结论:载利福平和异烟肼纳米粒表面完整光滑,无明显粘连现象,纳米粒均匀度好.亚微粒径分析仪测定纳米粒平均粒径80.4 nm.异烟肼载药量为(15.95±1.34)%,包封率为(5.01±0.17)%;利福平载药量为(4.66±0.97)%,包封率为(4.05±0.18)%.体外释药结果显示纳米粒的体外释药过程较平稳.突释期纳米粒中异烟肼释放度为15.22%,到3 d累积释放度可达95.6%;利福平释放度为9.26%,到3 d累积释放度可达90.3%.提示采用改良的自乳化二元溶剂扩散法制备载异烟肼和利福平纳米粒,所得载药纳米粒的粒径小且较均匀.纳米粒体外释药过程较平稳,无明显突释现象.     

鬼臼毒素-固体脂质纳米粒的皮肤毒理学实验

目的:考察鬼臼毒素-固体脂质纳米粒经皮肤用药的安全性。方法:实验于2005-12/2006-11在南方医科大学药学部实验室完成。选择Wistar大鼠140只,Fmmu豚鼠78只。采用改良的乳化蒸发-低温固化法制备5,50mg/L鬼臼毒素-固体脂质纳米粒及空白固体脂质纳米粒。①取豚鼠48只,按随机数字表法分成5,50mg/L鬼臼毒素-固体脂质纳米粒及空白固体脂质纳米粒完整皮肤组和破损皮肤组,每组4只,分别进行单次和多次给药皮肤刺激试验。单次给药方法:豚鼠背部两侧对称脱毛后用手术刀片作#字划痕,以渗血为度。采用同体左右侧自身对照法,左侧为受试区,分别取5,50mg/L鬼臼毒素-固体脂质纳米粒及空白固体脂质纳米粒混悬液0.1mL均匀涂布于受试区,右侧为空白对照区,再以自制单层塑料薄膜和双层纱布封包受试区。分别于去除敷料和清洗受试物后1,24,48h观察涂药部位有无红斑和水肿等情况,以及上述变化的恢复情况与时间。多次给药方法:皮肤处理方法、观察指标及评价指标同上,每日给药1次,连续给药14d。②取大鼠140只,按随机数字表法分成5,50mg/L鬼臼毒素-固体脂质纳米粒及空白固体脂质纳米粒完整皮肤组和破损皮肤组、正常对照组,每组10只,分别进行急性和长期皮肤毒性试验。急性毒性试验方法:脱毛后,分别取5,50mg/L鬼臼毒素-固体脂质纳米粒及空白固体脂质纳米粒混悬液1mL均匀涂布于受试区,连续观察14d,每日观察大鼠体质量、进食量、皮肤、呼吸、体态、眼、中枢神经系统、四肢活动、粪便性状及死亡情况。长期毒性实验方法:皮肤处理方法及观察指标同上,每日给药1次,药量均为0.1mL,连续给药30d,末次给药后24h麻醉后处死动物,取血3￣4mL进行血液学、血液生化学及皮肤病理检查。③取豚鼠30只,按随机数字表法分成50mg/L鬼臼毒素-固体脂质纳米粒组、阴性对照组及阳性对照组,每组10只,进行皮肤变态反应试验。方法:脱毛后,3组左侧脱毛区分别涂50mg/L鬼臼毒素-固体脂质纳米粒混悬液、空白固体脂质纳米粒混悬液及10g/L二四二硝基氯苯0.1mL,涂药后以自制单层塑料薄膜和双层纱布封包受试区,6h后去除敷料和清洗受试物。第7天和第14天,以同样方法各重复1次,共3次。于末次给受试物致敏后14d,将受试物0.1mL涂于豚鼠背部右侧脱毛区,6h后去掉受试物,即刻观察皮肤变态反应情况,之后于24,48,72h再次观察皮肤反应。结果:纳入大鼠140只,豚鼠78只,均进入结果分析。①单次和多次给予鬼臼毒素-固体脂质纳米粒对豚鼠完整和破损皮肤均无刺激作用。②单次大剂量给予5mg/L鬼臼毒素-固体脂质纳米粒及空白固体脂质纳米粒,未见对大鼠有急性毒性反应。给予50mg/L鬼臼毒素-固体脂质纳米粒组大鼠分别于给药后的前3,8d出现体质量减轻、食欲下降等全身中毒症状,尤以皮肤破损组表现较明显,以后逐渐恢复;每日小剂量给予5mg/L鬼臼毒素-固体脂质纳米粒及空白固体脂质纳米粒,未见对大鼠有明显长期毒性反应。③给予50mg/L鬼臼毒素-固体脂质纳米粒组大鼠于给药后的18￣25d,均出现轻度的皮肤红斑、水肿、糜烂和结痂等炎症反应,于停药后1周内消退,皮肤组织病理学检查可见以表皮为主的急性炎症反应;鬼臼毒素-固体脂质纳米粒对豚鼠皮肤无致敏性。结论:在有效观察时间和一定质量浓度范围内,鬼臼毒素-固体脂质纳米粒对豚鼠皮肤无刺激性及致敏性,对破损皮肤大鼠应用50mg/L鬼臼毒素-固体脂质纳米粒大剂量时易出现全身急性中毒反应而完整皮肤及5mg/L鬼臼毒素-固体脂质纳米粒应用则较安全,小剂量长期应用鬼臼毒素-固体脂质纳米粒对大鼠比较安全无系统吸收毒性,但应用50mg/L鬼臼毒素-固体脂质纳米粒时可以出现轻度的皮肤炎症反应。     

舒芬太尼固体脂质纳米粒的制备

目的 分析影响舒芬太尼脂质纳米粒制备的主要因素.方法 利用改良的乳化蒸发-低温固化技术,制备舒芬太尼固体脂质纳米粒混悬液,以单因素分析法筛选处方和工艺,并对该制剂表征进行考察.结果 制备的SUFSLN混悬液呈外观均一、稳定的半透明胶体状分散体系,略带淡蓝色乳光.平均粒径为(115.4±1.6)nm,Zeta电位为(-27.3±1.4)mv、包封率为(80.21±2.44)％.结论 改良的乳化蒸发-低温固化技术,可以用于制备舒芬太尼固体脂质纳米粒混悬液.     

阿克拉霉素A固体脂质纳米粒制备工艺研究

目的为促进固体脂质纳米粒的发展,拓宽阿克拉霉素A(ACM-A)制剂学研究内容。方法采用单因素试验初选阿克拉霉素A固体脂质纳米粒(ACM-SLN)的制备条件,并以正交设计优化了ACM-SLN的处方和制备工艺。结果得到的ACM-SLN的平均粒径为63 nm,平均载药量为(4.47±0.05)%,平均包封率为(89.32±0.91)%。结论以卵磷脂为载体材料制备ACM-SLN工艺简便,重现性好。     

鬼臼毒素-固体脂质纳米粒的制备及质量考察

目的:探讨鬼臼毒素-固体脂质纳米粒的制备方法及其质量。方法:实验于2005-12/2006-08在南方医科大学药学部实验室完成。在制备工艺研究上进行单因素考察和正交实验设计优化处方,以鬼臼毒素-固体脂质纳米粒粒径大小和Zeta电位、形态学、包封率、pH值作为样本质量考察指标,最终确定以改良的乳化蒸发-低温固化法制备鬼臼毒素-固体脂质纳米粒。实验评估:①用透射电镜考察纳米粒的形态。②用粒径分析仪检测纳米粒粒径大小和Zeta电位。③用高效液相色谱法测定纳米粒中鬼臼毒素的包封率。④用pH计测定鬼臼毒素-固体脂质纳米粒混悬液的pH值。结果:①鬼臼毒素-固体脂质纳米粒形态:基本呈圆形或椭圆形。②粒径大小和Zeta电位:分别为(75.3±26.2)nm,(23.2±3.1)mV。③包封率:86.4%。④pH值:4.66±0.18。结论:鬼臼毒素-固体脂质纳米粒制备工艺简单,考察制剂质量较理想。     

乳酸-羟基乙酸共聚物载药纳米粒的制备及体外释药性

背景:医用纳米粒作为药物传递的新型载体,目前已经成为医药领域研究的重点。目的:构建以生物可降解材料乳酸-羟基乙酸共聚物为载体,负载抗肿瘤药物5-氟尿嘧啶的载药纳米粒。方法:利用复乳-溶剂挥发法制备乳酸-羟基乙酸共聚物载药纳米粒。场发射扫描电子显微镜观察纳米粒表面形态;激光粒度分析仪测定粒径分布并计算成球率;紫外分光光度计测定5-氟尿嘧啶载药量、包封率,并对体外释药进行评估。结果与结论:纳米粒呈球性,平均粒径为(186±14)nm,成球率、载药量和包封率分别为70.8%、6.6%、28.1%,体外释药有突释现象,24h内5-氟尿嘧啶累积释药量达36.2%,10d达83.6%。提示成功制备乳酸-羟基乙酸共聚物载药纳米粒,其具有缓释效应。     

乳酸-羟基乙酸共聚物载药纳米粒的制备及体外释药性

背景：医用纳米粒作为药物传递的新型载体,目前已经成为医药领域研究的重点。目的：构建以生物可降解材料乳酸-羟基乙酸共聚物为载体,负载抗肿瘤药物5-氟尿嘧啶的载药纳米粒。方法：利用复乳-溶剂挥发法制备乳酸-羟基乙酸共聚物载药纳米粒。场发射扫描电子显微镜观察纳米粒表面形态;激光粒度分析仪测定粒径分布并计算成球率;紫外分光光度计测定5-氟尿嘧啶载药量、包封率,并对体外释药进行评估。结果与结论：纳米粒呈球性,平均粒径为（186±14）nm,成球率、载药量和包封率分别为70.8%、6.6%、28.1%,体外释药有突释现象,24h内5-氟尿嘧啶累积释药量达36.2%,10d达83.6%。提示成功制备乳酸-羟基乙酸共聚物载药纳米粒,其具有缓释效应。     

布洛芬磁性固体脂质纳米粒的制备

背景：布洛芬因溶解度和溶血问题,目前仍无注射给药剂型上市。目的：将自制的磁流体载入固体脂质纳米粒中,制备布洛芬磁性固体脂质纳米粒。方法：以包封率为指标,用正交设计确定布洛芬固体脂质纳米粒的最优处方。以共沉淀法制备Fe3O4磁流体作为磁性材料,采用乳化分散-超声法,按照最优处方制备布洛芬磁性固体脂质纳米粒。观察其表面形态、粒径大小、分布和Zeta电位、饱和磁化强度、包封率及体外释放特征。结果与结论：通过正交实验得最优处方为布洛芬0.05g、F-680.2g、吐温800.05g、卵磷脂0.1g、单硬脂酸甘油酯0.05g、磁流体2.5mL。用该工艺和处方制备的布洛芬磁性固体脂质纳米粒粒子呈均匀球形;平均粒径、zeta电位为（122±16）nm和（-13.3±6.94）mV;药物包封率和Fe3O4铁包封率分别为84.15%和83.19%;布洛芬在给定介质中36h释放较完全,符合制剂学性质要求。     

布洛芬磁性固体脂质纳米粒的制备

背景:布洛芬因溶解度和溶血问题,目前仍无注射给药剂型上市.目的:将自制的磁流体载入固体脂质纳米粒中,制备布洛芬磁性固体脂质纳米粒.方法:以包封率为指标,用正交设计确定布洛芬固体脂质纳米粒的最优处方.以共沉淀法制备Fe3O4磁流体作为磁性材料,采用乳化分散-超声法,按照最优处方制备布洛芬磁性固体脂质纳米粒.观察其表面形态、粒径大小、分布和Zeta电位、饱和磁化强度、包封率及体外释放特征.结果与结论:通过正交实验得最优处方为布洛芬0.05 g、F-68 0.2 g、吐温80 0.05 g、卵磷脂0.1 g、单硬脂酸甘油酯0.05 g、磁流体2.5 mL.用该工艺和处方制备的布洛芬磁性固体脂质纳米粒粒子呈均匀球形;平均粒径、zeta电位为(122±16) nm和(-13.3±6.94) mV;药物包封率和Fe3O4铁包封率分别为84.15%和83.19%;布洛芬在给定介质中36 h释放较完全,符合制剂学性质要求.     

鬼臼毒素固体脂质纳米粒冻干粉的制备及理化性质考察

目的:制备含有不同冻干保护剂的鬼臼毒素固体脂质纳米粒(POD-SLN)冻干粉,并考察其理化性质,筛选出最佳配方.方法:实验于2006-12/2007-11在南方医科大学药学部实验室完成.冻干配方为15%海藻糖、15%甘露醇和二者联用各取5%,冷冻干燥制作冻干粉制剂.扫描电镜下观察冻干粉复溶后粒子形态,Image-Pro Plus 6.0软件计算粒径大小,高效液相考察固体脂质纳米粒的药物包封率,并考察冻干粉的外观、复溶和4 ℃保存对其影响,评价不同辅料对冻干品的影响.结果:①外观和复溶情况:海藻糖冻干粉、海藻精联用甘露醇冻干粉表面均松脆多孔,疏松,复溶较快,约需20 s,甘露醇冻干粉表面较光滑,结构致密,饼状,复溶较慢,需借助外力.冻干粉样品4 ℃冰箱放置24h、1,3,6个月其外观和复溶均无明显变化.②电镜下粒子形态:呈圆形或椭圆形,分布较均匀,冻干前后无明显差异.③粒径:未加冻干保护剂时为(82.65±18.43) nm,加入海藻糖、海藻糖联用甘露醇、甘露醇后分别为(94.78±21.94), (109.26±16.15),(114.63±21.42) nm.④包封率:未加冻干保护剂时为87.4%,加入海藻糖、海藻糖联用甘露醇、甘露醇后分别为86.2%,80.3%,79.6%.结论:以15%海藻糖为冻干保护剂制备的鬼臼毒素固体脂质纳米粒冻干粉粒径较小,包封率高,稳定性好,其制备工艺合理可行.     

Improved tumor targeting and antitumor activity of camptothecin loaded solid lipid nanoparticles by preinjection of blank solid lipid nanoparticles

This study aimed to enhance the in vivo antitumor effects of camptothecin (CPT), a strong antitumor agent whose delivery is limited by poor aqueous solubility and instability of the active lactone form. CPT was loaded into sterically stabilized, solid lipid nanoparticles (CPT-SLNs) formulated for intravenous administration. The influence of preinjected blank SLNs on the tumor targeting, pharmacokinetics and antitumor activity of CPT-SLNs was investigated. The CPT-SLNs composed of trilaurin-based lipid matrix containing poloxamer188 and pegylated phospholipid as stabilizers were prepared by hot homogenization method and evaluated for in vitro characteristics and in vivo performance. The CPT-SLNs showed an in vitro long-term sustained release pattern and effectively protected the CPT lactone form from hydrolysis under physiological conditions. Notable tumor targeting and tumor growth inhibition were observed after intravenous administration of CPT-SLNs to mice with subcutaneous transplants of CT26 carcinoma cells. In pharmacokinetic studies in rats, CPT-SLNs markedly elevated plasma CPT level and prolonged blood circulation compared to free CPT. Nonetheless, high uptake of CPT-SLNs by reticuloendothelial system (RES)-rich tissues resulted in limited tumor targeting of CPT-SLNs and plasma CPT levels. Preinjection of blank SLNs before administration of CPT-SLNs to tumor-bearing mice substantially reduced the accumulation of CPT-SLNs in RES organs. This led to significantly enhanced tumor targeting, improved pharmacokinetic parameters and increased antitumor efficacy of CPT-SLNs. These results suggested that the in vivo antitumor effects of CPT-SLNs could be further enhanced by preinjection of blank SLNs. Therefore, CPT-SLNs with preinjected blank SLNs could be a potential approach for stable and effective CPT-based cancer therapy.     

Molecular interactions, internal structure and drug release kinetics of rationally developed polymer–lipid hybrid nanoparticles

This paper presents the first study of molecular interactions of ingredients and internal nanostructure in relation to drug loading and release mechanisms/kinetics of rationally designed solid polymer–lipid hybrid nanoparticles (PLN). The PLN were prepared by using a rationally selected composition that was found in our previous work to provide optimized interactions of verapamil hydrochloride (VRP) with dextran sulfate sodium (DS) and then the VRP–DS complex with dodecanoic acid (DA). The solid-state properties of the components, their molecular interactions and the morphology, particle size and internal structure of PLN were determined by use of differential scanning calorimetry, powder X-ray diffraction, ¹³C nuclear magnetic resonance, Fourier transform infrared spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering. The distribution of VRP in PLN was examined by TEM imaging using a cationic gold tracer. Drug release studies were conducted in various media. Drug loading as high as 36% and loading efficiencies up to 99% were achieved in the rationally formulated PLN. Hydrogen bonding between drug, polymer and lipid and a uniform distribution of amorphous VRP within the solid lipid matrix were evident. Sustained drug release from the PLN was mainly controlled by ion exchange and diffusion processes. The results demonstrated that strong molecular interactions among the drug, the polymer and the lipid in the optimized formulation were responsible for the improved drug loading and release performance of the PLN.     

Etoposide loaded solid lipid nanoparticles for curtailing B16F10 melanoma colonization in lung

Poor solubility of etoposide and associated poor bioavailability of the drug was circumvented by developing solid lipid nanocarrier system. The objective of the research work was to prepare etoposide loaded solid lipid nanoparticles (SLN) for improved efficacy and therapy of metastasized cancers. Entrapment of drug into nanoparticulate system modifies the pharmacokinetic and biodistribution profile of the drug with improved therapeutic efficacy. Solid lipid nanoparticles of various triglycerides were prepared using hot homogenization technique. Further, the process and formulation parameters viz. homogenization cycle and pressure, type of lipid were optimized. Developed nanoparticles were characterised for particle size, in vitro dissolution studies, DSC thermogram, surface morphology and cytotoxicity assay. Pharmacokinetic and biodistribution study were performed to assess the distribution of the drug in vivo. Modulation of the therapeutic activity of the drug was studied by performing antimetastatic activity on a B16F10 melanoma mouse model. The obtained results exhibited suitability of trimysristin for fabrication of nanoparticles. Characterisation of nanoparticles depicted formation of homogenous, spherical particles entrapping approximately 50% of the drug. The results for the performed MTT assay suggested that the developed nanoparticles exhibited cytotoxicity in a time- and concentration-dependent fashion. These findings concord with the results of the in vitro dissolution profile. Pharmacokinetic parameters demonstrated increase in area under curve (AUC), t_1/2 and mean residence time (MRT) for drug in plasma. Further there is enhancement in the ratio of the drug that reaches to the highly perfused organs (upon encapsulation into solid lipid nanoparticles). Generally, cancer cells metastasized through the blood or lymphatic system. Accumulation of the drug in the highly perfused organ suggests suitability of the developed nanoparticles for targeting metastasized tumors. This was proved by the findings of the in vivo B16F10 mouse melanoma model. Improvement in the tumoricidal activity and survival rate of the animals substantiates the application of nanoparticles for improved therapeutic activity of etoposide.     

Preparation, characterization and in vitro release kinetics of clozapine solid lipid nanoparticles.

Clozapine, a lipophilic antipsychotic drug, has very poor oral bioavailability (<27%) due to first pass effect. Solid lipid nanoparticle (SLN) delivery systems of clozapine have been developed using various triglycerides (trimyristin, tripalmitin and tristearin), soylecithin 95%, poloxamer 188 and charge modifier stearylamine. Hot homogenization of melted lipids and aqueous phase followed by ultrasonication at temperature above the melting point of lipid was used to prepare SLN dispersions. Particle size and zeta potential were measured by photon correlation spectroscopy (PCS) using Malvern Zetasizer. Process and formulation variables have been studied and optimized. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies were performed to characterize state of drug and lipid modification. In vitro release studies were performed in 0.1 N HCl, double-distilled water and phosphate buffer, pH 7.4, using modified Franz diffusion cell. Stable SLN formulations of clozapine having mean size range of 60-380 nm and zeta potential range of -23 to +33 mV were developed. More than 90% clozapine was entrapped in SLN. DSC and PXRD analysis showed that clozapine is dispersed in SLN in an amorphous state. The release pattern of drug is analyzed and found to follow Weibull and Higuchi equations.     

盐酸哌甲酯缓释微丸胶囊剂的研制与体外释放

目的制备一种盐酸哌甲酯（MPH）缓释微丸胶囊剂,并与进口控释片专注达。体外释放情况进行比较研究。方法利用流化床包衣技术制备一种含有3种不同释药速率微丸的MPH缓释微丸胶囊剂：将部分载药微丸包保护层后制成速释微丸;以乙基纤维素（Surelease。）为缓释材料制备单层缓释微丸;通过内包溶胀层（欧巴代-7006,主成分为低黏度羟丙基甲基纤维素（HPMC）,外加控释层制备具有时滞的双层择时缓释微丸。在模拟胃肠道pH值介质中比较自制胶囊剂与控释片的体外释药情况。结果载药微丸实际载药量6．85％。单层缓释微丸包衣增重14％;双层择时缓释微丸溶胀层包衣增重16％,控释层包衣增重22％,时滞约3．5h。3种微丸按以下比例混合后装胶囊：速释微丸含MPH22％,单层缓释微丸含MPH39％,双层择时缓释微丸含MPH39％。该胶囊剂1h释放可达25％,4h释放约50％,12h释放〉95％。两制剂在模拟胃肠道介质中的释放曲线相似。结论制备出一种由3种微丸组成的,能连续12h释药的MPH缓释微丸胶囊剂,其工艺简单,与进口控释片专注达。有相同的体外释放效果。     

人胎关节软骨细胞体外培养的生物学特性

目的:研究软骨组织工程中传代软骨细胞与原代的差异。方法:用5个月人胎关节软骨分离培养细胞,观察细胞存活率、贴壁率、生长曲线和组织形态学的改变。结果:(1)软骨块在4℃下,3d 内细胞存活率可达 93.4％～97.6％。(2)原代细胞为圆形或三角形;第4代有一半转变成梭形,到第6代全部变为长梭形。(3)传代细胞贴壁时间(2～3h)短于原代(4～7h)。玻璃瓶内贴壁率传代细胞为78.7％～85.5％,原代8.8％。(4)生长曲线表明,从原代到第4代都有高增殖力;到第8代时增殖降低;到第12代几乎丧失细胞增殖。结论:软骨块4℃冷藏,3d内对细胞存活率无明显影响。第4代细胞贴壁快、增殖快,适于作为组织工程用细胞。第8代以后不适合。     

去炎松-A固体脂质纳米颗粒透皮吸收在瘢痕治疗中的效应

目的:为克服目前瘢痕非手术治疗中糖皮质激素治疗的副作用,尝试应用去炎松-A固体脂质纳米颗粒经透皮吸收技术治疗瘢痕,观察其效果.方法: 实验于2007-04/08在解放军兰州军区总医院动物实验中心实验室进行.①造模:选用新西兰白兔16只,每个兔耳上将全层皮肤切除,形成1 cm×1 cm上、下两个创面,术后30 d上皮化生逐渐形成病理性瘢痕.②分组干预:造模成功后随机分为对照组和实验组,每组8只.对照组不干预,实验组于术后30 d起应用含有去炎松-A 1 mg/cm2 的固体脂质纳米颗粒卡波姆凝胶覆于已形成的瘢痕上透皮吸收.③观察指标:分别于模型形成后第30,60,90和120天时依次取每只大白兔左耳上、下,右耳上、下的病理性瘢痕作为标本来源进行组织病理学观察,同时采用免疫组化检测组织中的ki-67表达和羟脯氨酸含量,并抽静脉血测血中皮质醇浓度.结果:16只白兔均进入结果分析.①实验组做模型后第30天时ki-67表达及羟脯氨酸含量与对照组比较无明显差异(P > 0.05),但第60,90和120天实验组瘢痕组织中表达及羟脯氨酸含量较对照组明显减少(P < 0.01).②实验组及对照组各时段血中的皮质醇浓度比较无明显差异(P > 0.05).③实验组造模后120 d病理性瘢痕中成纤维细胞的数量少于对照组.结论:含有去炎松-A 1 mg/cm2 的固体脂质纳米颗粒卡波姆凝胶透皮吸收对瘢痕有治疗作用,且长期应用血液中的皮质醇浓度不升高,能预防糖皮质激素治疗瘢痕的副作用.     

聚乳酸-羟基乙酸包载眼镜蛇毒细胞毒素缓释微球的表征及体外释放行为

背景:眼镜蛇毒细胞毒素具有强烈的细胞毒活性,但缺乏特异性,全身用药可导致严重毒副作用,而采用缓释载体包载进行间质化疗可达到提高肿瘤局部治疗效应,并且减轻全身毒性.目的:制备眼镜蛇毒细胞毒素一聚乳酸-羟基乙酸微球,观察其一般性质和体外释约特性.设计、时间及地点:观察性实验,于2007-12/2008-05在福建医科大学医药生物工程中心完成.材料:聚乳酸-羟基乙酸、聚乙烯醇由中国科学院成都有机化学有限公司提供,广东产中华眼镜蛇毒.方法:采用分子筛、离子交换分离,反相疏水高效液相色谱方法纯化细胞毒素,MTT法榆测细胞毒活性,复乳-溶剂挥发法制备载药微球.主要观察指标:扫描电镜观察载药微球的表面形态,激光粒径仪测微球粒径,计算包封率、载药量、体外释放周期.结果:纯化的眼镜蛇细胞毒素具有明显的细胞毒作用,对HepG2细胞12,24 h的IC50分别为1.43,1.12 mg/L.复乳法制备微球表面光滑圆整,粒径2～8 μ m,包封率和载药率分别为(74.10±9.92)%和(0.72±0.09)%,21 d药物累积释放63.3%,释放细胞毒素保持较好的生物学活性.结论:采用复乳一溶剂挥发法可制备具有较高包封率、良好缓释效果、保持完整生物学活性的眼镜蛇毒细胞毒素-聚乳酸-羟基乙酸微球.     

碘化油在离体子宫肌瘤声学显影特性的实验研究

目的 探讨碘化油在离体子宫肌瘤组织内的显影效果及弥散规律,为碘化油联合高强度聚焦超声（HIFU）治疗子宫肌瘤提供理论依据和实验数据.方法 将40枚离体子宫肌瘤随机均分为实验组和对照组,实验组瘤体中心注入碘化油1 ml,记录注入后即刻,10 、20 、30 、40 、70 、110 min瘤体中碘化油形成的团状强回声的超声灰度值和灰度面积;对照组以生理盐水代替碘化油,除不测定B型超声灰度面积外,余同实验组.结果 实验组碘化油注入即刻,B型超声灰度值最大（75.1±7.7）dB,然后逐渐下降、消失.对照组注入生理盐水后灰度未见明显增加,也未表现出随时间变化的规律性.实验组B型超声灰度面积在碘化油注入后呈类似同心圆增大,至30 min达最大值,后逐渐变小、消失.结论 碘化油在离体子宫肌瘤组织中具有明显的声学显影作用和缓慢的弥散性,该特性可用于碘化油联合HIFU治疗子宫肌瘤的实际临床应用中.