载药肿瘤微血管栓塞颗粒制备及其抗肿瘤作用初探

目的 制备加载化疗药物的纳米微粒,研究其性质及体外释药特点,探讨体外对人原代肝癌细胞的毒性作用,为用于临床肿瘤微血管介入栓塞提供理论依据.方法 以盐酸吉西他滨-复方甘草酸苷共聚物为药物载体,加载化疗药物多柔比星制备载药纳米微粒.扫描电镜观察微粒形态,纳米粒度电位仪检测微粒粒径分布及电位,高效液相色谱法计算载药率及包封率,透析袋扩散法作体外释放动力学试验,体外考察纳米药物稳定性及释药性能.CCK-8法检测纳米药物在体外对人原代肝癌细胞的毒性作用.结果 本法制备的载药纳米微粒外观呈圆球形,平均粒径(62.83±5.19) nm,平均电位-17.9 mV;载药率、包封率分别为3.16％、66.27％;有良好的缓释特性,对人原代肝癌细胞生长有明显抑制作用.结论 本法制备的载药纳米微粒具有较好的药物缓释性及抗肿瘤效应,是一种具有良好应用前景的抗肿瘤纳米药物.     

盐酸二甲双胍壳聚糖-海藻酸钠缓释微囊的制备及性能研究

目的 制备盐酸二甲双胍壳聚糖-海藻酸钠缓释微囊并探索其性能.方法 以壳聚糖和海藻酸钠为囊材,利用复凝聚法将盐酸二甲双胍微囊化.以微囊的药物包封率为制备工艺优化指标,用转篮法测定其体外溶出速率.结果 通过正交实验得出微囊的最佳制备工艺条件为:壳聚糖浓度0.2%,成囊pH 4.5,成囊温度45℃,搅拌速度200r/min.微囊的溶出释放性能实验显示,该载药微囊的累积释放速度远低于市售缓释片剂,在20h左右达到75%左右的最高累积释放值.结论 以最佳制备工艺条件制备含药微囊重现性好、工艺稳定、吸水溶胀性好,体外溶出实验显示具有较好的缓释作用.     

不同微型药物载体对扑热息痛体外经皮吸收的影响

 目的 考察微乳、微囊、脂质体不同微型药物载体对扑热息痛体外经皮渗透的影响.方法 使用Franz体外释药装置,采用紫外分光光度法检测接受液中扑热息痛的浓度并计算药物的经皮累积释放量.结果 在体外经皮释放试验中,扑热息痛经皮制剂的不同给药载体经皮吸收效果差异明显,不同给药载体经皮吸收试验的体外渗透参数表明,脂质体和微囊的经皮吸收效果明显优于微乳,差异有统计学意义(P<0.05).结论 微囊更适宜作为扑热息痛经皮制剂的给药载体.     

氟尿嘧啶纳米乳剂的制备与性质

目的研究氟尿嘧啶大豆油纳米乳剂的相图、稳定性、载药量及药物的体外释放特点。方法在三元相图的基础上优选出制备纳米乳剂的最佳处方,用透射电子显微镜观测纳米乳剂粒径的大小,HPLC法测定纳米乳剂中氟尿嘧啶的含量及体外释放性能。结果纳米乳剂颗粒为圆形或椭圆形,粒径范围20±10nm,药物包裹率85.06%,体外11h药物释放50%,50h缓释95%。结论本实验制备的纳米乳剂性质稳定,与游离的药物相比有明显的缓释性能。     

奥沙利铂长循环热敏脂质体的包封率测定及体外释放考察

目的:建立奥沙利铂脂质体的包封率和含量测定方法,并对其体外释放进行考察.方法:采用逆相蒸发法制备奥沙利铂脂质体,用葡聚糖凝胶G-50柱分离载药脂质体和游离药物,以水为洗脱液,RP-HPLC法测定包封率,采用透析法考察脂质体在37℃和41℃的体外释放规律.结果:柱层析分离方法的药物回收率为99.25%,柱加样回收率为100.37%;药物含量测定方法的工作曲线为A =3E 06c-3290.8(n=5),r=0.9999,线性范围0.0201～2.0100 mg/ml,方法回收率为100.70%;脂质体在41℃条件下的释放规律符合一级动力学过程.结论:本方法简便、灵敏、准确,可以用于测定奥沙利铂脂质体的含量和包封率,所制得的脂质体具有明显的热敏释放特征.     

阿霉素磷脂毫微粒复合体的制备及药剂学特征研究

目的　制备阿霉素磷脂毫微粒复合体。方法　采用均匀设计等方法筛选处方和工艺。先制备阿霉素聚氰基丙烯酸正丁酯毫微粒 ,再采用磷脂双分子层包裹 ,得到阿霉素磷脂毫微粒复合体。结果　制得的磷脂毫微粒复合体的平均包封率为(86 .6 5± 0 .97% ) ,平均粒径为 2 5 6 .2nm。稳定性较普通脂质体好 ,包封率比普通毫微粒高。结论　阿霉素磷脂毫微粒复合体达到设计要求 ,有可能成为一种新的药物靶向载体给药系统     

口服脉冲给药系统简介

脉冲给药系统被定义为按预定的模式迅速而短暂地释放定量的药物,并且能迅速停止释放的给药系统。脉冲释放与人体内激素的生理释放相似,如胰岛素等激素的释放,在基线释放中就包含了脉冲的、短暂的突释型的释放。对病情发作具有节律性,而不需长时间维持体内恒定药物浓度的疾病,如高血压、心绞痛、支气管哮喘、风湿、糖尿病等,脉冲给药不仅疗效很好,而且降低了药物的不良反应。口服脉冲给药系统通过控制释放时间还可达到定位释放的作用,临床应用前景良好。为此,笔者综述国内外的相关文献,供药学和医学专业的同道参考。     

载万古霉素硅溶胶涂层的制备及其体外抑菌作用观察

目的 制备载万古霉素硅溶胶(VCM-SOL)涂层,探讨其体外缓释、降解和抑菌性能.方法 采用正硅酸乙酯酸化水解法制备硅溶胶(SOL),以其作为药物载体负载万古霉素(VCM),制备VCM浓度分别为10、20、30mg/ml的VCM-SOL涂层.通过高效液相色谱方法测定VCM体外释放浓度,洗脱法观察涂层的体外降解行为,选用金黄色葡萄球菌作为试验菌,分别观察载有不同浓度药物的VCM-SOL钛钢片和载SOL钛钢片的体外抗菌效果.结果 载药浓度为20mg/ml的VCM-SOL具有良好的体外释放和降解效果,第14天时洗提液中VCM浓度为5.5±1.4μg/ml,仍高于金黄色葡萄球菌的最小抑菌浓度(1.56～3.12μg/ml),其失重率为84.72%,而第14天时载药浓度为10mg/ml及30mg/ml的VCM-SOL洗提液中VCM浓度分别为1.5±0.5和1.0±0.2μg/ml,失重率分别为77.39%和96.08%.抑菌试验显示,所有VCM-SOL钛钢片周围均有明显的抑菌圈,而载SOL钛钢片周围未见抑菌圈.结论 载VCM-SOL涂层的制备效果满意,具有明显的缓释和抑菌作用,其释放速度和降解率可通过改变载药浓度进行控制,有望为临床上预防及治疗开放性骨折和假体置换术后细菌感染提供新的途径.     

戊二醛对长春新碱载体红细胞生物学特性的影响

目的 探讨控制长春新碱(VCR)载体红细胞体外药物释放,增强载体红细胞稳定性的方法和条件.方法 采用改良的低渗预膨胀-等渗重封闭法制备VCR载体红细胞,分别用0.16%和0.25%戊二醛溶液进行处理,同时将载体红细胞悬液与药量PBS混匀作为对照组.通过4℃保存定时提取上清液,以高效液相色谱法测定VCR含量,比较不同处理方式对VCR载体红细胞载药释放的影响,通过观察上清液可见溶血和细胞渗透脆性检测,比较各种方式处理后VCR载体红细胞的贮存稳定性和渗透脆性,并观察处理后VCR载体红细胞的形态变化.结果 各组VCR载体红细胞的载药累积释放均随时间延长而逐渐增大.与对照组相比,.25%戊二醛溶液处理组载药累积释放下降了71.67%±4.20%,稳定贮存时间由5天延长至21天,差异有显著性(P＜0.01),渗透脆性和细胞形态无明显改变;0.16%戊二醛溶液处理组载药累积释放无明显变化,稳定贮存时间增加至7.5天,而渗透脆性有所增大.结论 0.25%戊二醛溶液对人源VCR载体红细胞具有较好的细胞膜封闭和稳定作用.     

胃内漂浮控释片简介

<正> 所有口服给药如不能在吸收部位滞留足够的时间,则它的应用是有限的。欲延长药物在消化道的滞留时间,则将药物制成在胃内能漂浮的制剂形式是较理想的。此种制剂是利用浮力使制剂于胃内漂浮,不受胃排空的影响,延长药物在胃内的滞留时间,延缓药物的释放,使释药速率低于药物进入组织、血液的最大速度,提高了药物的生物利用度。药物在胃内能够漂浮的缓释制剂形式通常称为胃内漂浮控释给药系统(Hydrodynamically Balanced System),简称HBS利用物理法(还有生理法及药理法)制备的HBS可分为:凝胶漂浮给药系统和漂浮装置控释给药系统两大类。后者又可分为漂浮室型和漂浮筏型控释给药系统两种。本文拟就凝胶漂浮给药系统做一简单介绍。     

PLGA微米与纳米载药颗粒用于药物携带与递送的比较研究

 

目的 通过评价聚乳酸-羟基乙酸共聚物(polylactic acid-glycolic acid copolymer,PLGA)微米颗粒(micron particle,MP)与纳米颗粒(nanoparticle,NP)的表面特征、载药能力、药物缓释能力及细胞吞噬能力等方面来比较阐述PLGA纳米与微米颗粒在细胞预处理与修饰中的合理应用。方法 分别制备PLGA纳米颗粒与微米颗粒,并进行表征;随后,比较其载药能力,并对药物的释放特征进行测定;最后,在不同时间点通过荧光强度评价两种颗粒与细胞结合或进入细胞的能力。结果 所制备的纳米粒与微米颗粒粒径分别分布在200~300 nm和2~4 μm;两种颗粒载药量相当,分别为14.3%和14.1%;在药物缓释方面,纳米颗粒存在显著的早期突释现象;微米颗粒释放缓慢,持续缓释可达一周左右;粒径相对小的纳米粒更容易进入或与细胞结合,共孵育12 h即达到最大值,微米颗粒相对较慢,最大值出现在共孵育24 h后。结论 PLGA纳米颗粒作为药物载体更适合于急性组织或细胞保护,微米颗粒更适合于慢性持续性保护。

     

盐酸表柔比星长循环热敏冻干脂质体的处方工艺研究与体外释药机制探讨

目的研究盐酸表柔比星长循环热敏冻干脂质体（EPI-LTSL）的处方工艺,并探讨其体外释药机制。方法pH梯度法制备EPI-LTSL并进行冷冻干燥,正交试验优化处方,单因素试验优化工艺。通过观察不同温度下EPI在不同介质中形成沉淀的性状,探索EPI-LTSL的体外释药机制。结果最佳处方及工艺为药脂比1∶10,DPPC/MSPC为82∶8,水化介质为250mmol/L柠檬酸盐（pH4.0）。空白脂质体经15000psi（103MPa）高压均质循环5～6次,100nm聚碳酸酯膜挤压过膜3次;调节脂质体外相pH后,35℃水浴20min载药。冻干脂质体内外相乳糖浓度为9%,采用中速预冻（-65℃）及缓慢的解吸干燥可以制备较好的冻干品。EPI与柠檬酸盐形成的沉淀在42℃可以完全溶解,而在25℃成絮状或片状沉淀。结论制备的EPI-LTSL载药量和包封率较高,粒径较小。冻干脂质体外观平整,内部疏松多孔,色泽鲜亮,复水迅速且粒径变化较小。以柠檬酸盐为水化介质制备的EPI-LTSL,在25℃时包载于脂质体内相的EPI以沉淀稳定存在,而在42℃时可完全溶解释放出来。     

Patterns of illicit drug use of prisoners in police custody in London, UK

AIMS AND METHODS: The aims of the study were to explore the current characteristics of drug misusers seen in police custody and identify trends or changes that have taken place in the last decade. A prospective, anonymised, structured questionnaire survey was undertaken of consenting consecutive, self-admitted illicit drug users seen by forensic physicians in police custody within the Metropolitan Police Service in London, UK in 2003. RESULTS: 30% of detainees were dependent on heroin or crack cocaine. Drug users (n=113) were studied in 2003. 95.4% completed the questionnaire. 82% were male, 18% female. Mean age was 28.5 y (range 18-49). 80% were unemployed; significant mental health issues (e.g., schizophrenia) were present in 18%; 15% had alcohol dependence; heroin was the most frequently used drug (93%); crack cocaine -- 87%; mean daily cost of drugs -- heroin GBP 76 (range 20-240), crack GBP 81 (range 20-300). >50% users inject crack and heroin simultaneously. 56% used the intravenous route; 25% had shared needles; 100% had accessible sources of clean needles; 6.4% were hepatitis B positive; 42% were aware of hepatitis prophylaxis; hepatitis C positive -- 20.2%; 3.6% were HIV positive. Mean length of time of drug use was 7.5 y (range 1 month -- 20 years); 82% had served a previous prison sentence; 54% had used drugs in prison; 11% had used needles in prison; 3% of users stated they had started using in prison. 38% had been on rehabilitation programs; 11% had been on Drug Treatment and Testing; Orders (DTTO); 32% had used the services of Drug Arrest Referral Teams in police stations; 10% were in contact with Drug Teams at the time of assessment. CONCLUSIONS: In the last decade, there appears to be a substantial increase in the prevalence of drug use in this population -- particularly of crack cocaine. Treatment interventions are either not readily available, or not followed through. In very general terms, the illicit drug use problem appears to have significantly worsened in the population seen in police custody in London, UK, in the last decade although there is evidence that health education and harm reduction messages appear to have had some positive effects.     

MR imaging of biodegradable polymeric microparticles: a potential method of monitoring local drug delivery.

Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) was encapsulated into biodegradable, bioadhesive polymeric microparticles to enable noninvasive monitoring of their local intravesical delivery with MRI. The microparticles were characterized by contrast agent encapsulation and release kinetics, T(1) relaxation rates, and contrast enhancement in vivo. The level of Gd-DTPA loading into microparticles was 14.3 +/- 0.6 mug/mg polymer. The measured T(1) relaxation rates of the microparticles showed a direct dependence on Gd-DPTA content. Both 1.5T and 4.7T MR scanners were used to image murine bladders instilled intravesically with Gd-DTPA-loaded particles in vivo. MR images showed ring-shaped regions of enhancement inscribing the bladder wall, which were attributed to the microparticles that were preferentially adherent to the mucosa lining the urothelium. The images of controls exhibited no such enhancement. The normalized signal intensities measured from post-instillation images were significantly greater (P < 0.05) than those in the pre-instillation images. Contrast enhancement was observed for at least 5 days after the initial instillation, although the enhancement decreased due to microparticle degradation or mucosa renewal. The localized distribution of biodegradable, bioadhesive microparticles encapsulating Gd-DTPA was successfully visualized with MRI in vivo, allowing particle-mediated delivery to be temporally and spatially monitored noninvasively.     

制片工艺对芦丁缓释骨架片释药机制影响研究

目的：考察制片工艺对芦丁缓释骨架片释药机制的影响情况。方法：以羟丙基甲基纤维素(HPMC)为骨架材料制备缓释骨架片，利用Peppas经验式释放指数n值，评价制片工艺对芦丁缓释骨架片体外释药机制的影响。结果：干法制片的释药比湿法快。结论：干法制片与湿法制片有相同的释药机制。     

In vitro echogenicity characterization of poly[lactide-coglycolide] (plga) microparticles and preliminary in vivo ultrasound enhancement study for ultrasound contrast agent application

OBJECTIVES: This work includes (1) the characterization of a reproducible poly[lactide-coglycolide] (PLGA) microparticle preparation with an optimial mean diameter and size distribution and (2) the preliminary in vivo ultrasonographic investigation of PLGA microparticles. METHODS: A first series of PLGA microparticle preparations (1 to 15 mum) was acoustically characterized on a hydrodynamic device to select the most appropriate for ultrasound contrast agent application. Preparations of 3-microm microparticles were selected, characterized at different doses, and then injected into 20 melanoma grafted mice for contrast-enhanced power Doppler ultrasonography evaluation. RESULTS: The 3-microm microparticles (3.26-microm mean diameter with 0.41-microm standard deviation) led to in vitro enhancement of 18.3 dB at 0.62 mg/mL. In vivo experiments showed 47% enhancement of intratumoral vascularization detection after PLGA injection, significantly correlated (P < 0.0001) with preinjection intravascularization and tumoral volume. No toxicity was histologically observed. CONCLUSION: The 3-microm PLGA microparticles provided significant enhancement in vitro and in vivo without any toxicity.     

瓜耳胶-g-异丙基丙烯酰胺水凝胶中盐酸青藤碱释放性质研究

目的研究接枝共聚物瓜耳胶-g-异丙基丙烯酰胺（GPNA）水凝胶中盐酸青藤碱释放特征。方法采用Franz-Chien扩散池进行凝胶中药物扩散实验。分别考察释放介质温度、离子强度、pH及交联剂含量对凝胶中药物释放的影响。结果温度、pH、交联剂含量、离子强度对药物的释放均有影响；凝胶中药物在0.1mol·L^-1HCl中释放速度明显快于在0.1mol·L^-1 pH 6.8 PBS中释放速率。温度低于聚合物LCST值时，药物释放没有显著性差异；温度高于聚合物的LCST值时，随着水凝聚的收缩，表面“皮层”逐渐形成，凝胶释药减慢。凝胶中药物药物释放随离子强度及交联剂含量的增加而减慢。结论GPNA水凝胶具有明显的温度及pH敏感性，可用作智能给药的药物载体。     

酮洛芬聚氰基丙烯酸正丁酯毫微粒制备工艺研究

目的：制备酮洛芬聚氰基丙烯酸正丁酯毫微粒（ KP-PBCA-NP）。方法：采用乳化聚合法制备空白PBCA—NP，以粒径为指标，应用L9（3^4）正交试验优化处方工艺；吸附法制备KP—PBCA—NP，以包封率、载药量为指标，应用U10（10^8）均匀法设计实验，进行条件优化。结果：制备PBCA—NP的优化条件为反应液pH2～3，Pluronic F68的含量为1．0％～1．5％，优化条件下制备PBCA—NP平均粒径为50nm；在制备KP-PBCA—NP时，当反应液的pH值为1，PBCA含量为0．5％，KP含量为0．8mg／ml时，可获得较高的包封率（平均为95．64％）和载药量（15．32％）。结论：控制工艺条件，可制备不同粒径的PBCA—NP作为各种药物载体，并且可以从此为载体制备可用于注射给药的KP—PBCA—NP。     

复方茵陈注射液与几种注射液的配伍稳定性考察

目的考察复方茵陈注射液在5%葡萄糖注射液等3种注射液中的配伍稳定性。方法将复方茵陈注射液加入到3种注射液中,采用临床用药浓度和配制方法,在配伍后不同时间,用高效液相色谱法检测配伍液的栀子苷含量,同时检查配伍液的pH值、微粒、澄明度。结果复方茵陈注射液与3种注射液配伍后在室温放置8 h,其pH、澄明度、含量、微粒等指标均无明显异常。结论复方茵陈注射液与5%葡萄糖注射液、10%葡萄糖注射液、氯化钠注射液配伍,8 h内稳定,临床应用时可与上述注射液配伍。     

High-dose-rate brachytherapy with local injection of bleomycin for N0 oral tongue cancer--possibilities of the control of tumor implant by inserting applicators and the decrease in tumor dose

Twenty-eight patients with N0 oral tongue cancer were treated with high-dose-rate (HDR) interstitial brachytherapy combined with local injection of bleomycin between December 1997 and June 2001 at the Department of Radiology, National Kyushu Medical Center Hospital. A median dose of 5 mg of bleomycin was injected locally, and 16-20 Gy was delivered to the area surrounding applicators for control of the tumor implant during the initial two days. The two-year local recurrence-free survival rate was 96% [T1, 2: 100% (8/8, 15/15), T3: 80% (4/5)]. The two-year secondary neck node metastasis rate was 7.1% [T1: 12.5% (1/8), T2: 6.7% (1/15), T3:0% (0/5)]. There were no tumor implants in any patients. We tried to decrease the minimal tumor dose step by step. The groups with median minimal tumor doses of 60 Gy, 50 Gy, and 40 Gy had local recurrence rates of 12.5% (1/8), 0% (0/14), and 0% (0/6), respectively. Local recurrence rates were not increased by decreasing the minimal tumor dose. Two patients (7%) had secondary neck node metastasis. Late adverse effects were tongue ulcer: 11% (3/28), oral floor ulcer: 4% (1/28), and osteonecrosis: 4% (1/28). These results suggest that control of the tumor implant and the decrease in minimal tumor dose below 60 Gy may be possible with the local injection of bleomycin and delivery of doses to the area surrounding the applicators when NO tongue cancer is treated using 192Ir-HDR brachytherapy.