载羟基喜树碱纳米粒的制备和体外评价

目的:制备壳寡糖接枝布洛芬(COS-g-IBU)纳米粒负载羟基喜树碱(HCPT)纳米粒,并考察其体外释药性能。方法:以1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)为偶联剂,制备壳寡糖接枝布洛芬纳米粒(COS-g-IBU NPs)。以COS-g-IBU NPs为载体,使用超声振荡技术制备负载HCPT的壳寡糖接枝布洛芬纳米粒(HCPT-COS-g-IBU NPs)。结果:透射电镜照片显示COS-g-IBU NPs和HCPT-COS-g-IBU NPs为球形,平均粒径分别为(116±2)nm和(146±5)nm,测得药物包封率为(79.24±1.18)%,载药量为(3.62±0.05)%,体外药物释放试验表明HCPT-COS-g-IBU NPs具有明显的缓释作用。结论:COS-g-IBU可作为HCPT缓释载体材料。     

羟基喜树碱半固体脂质纳米粒的制备和体外释药特性

目的：制备羟基喜树碱的半固体脂质纳米粒（HCPT-SSLN），初步考察其体外释药规律。方法：采用乳化蒸发-低温固化法制备HCPT-SSLN；用激光粒度仪测定其粒径和ξ电位；考察其混悬液和冻千粉的物理稳定性；用透析法考察其体外释药性质。结果：HCPT-SSLN纳米粒平均粒径为130．5nm，裁药量为2．51％，包封率为79．19％，ξ电位为-33．1mV;室温（25℃）和4℃下放置6个月，纳米粒冻干粉和混悬液外观、粒径及包封率无明显变化；体外释药规律符合Weibull方程lnln[1／（1-Q）]=0．26331nt＋0．0509（R^2=0．9485）。结论：制备的HCPT-SSLN包封率高，稳定性好，大小均匀，体外释药具有缓释特点。     

羟基喜树碱半固体脂质纳米粒的体外药剂学性质研究

目的：制备羟基喜树碱的半固体脂质纳米粒(HCPT-SSLN)。方法：在单因素考察的基础上,通过正交设计优选处方和制备工艺,并对优化条件下制备的HCPT-SSLN进行质量评价。结果：制备的HCPT-SSLN平均粒径为130.5 nm,多分散系数为0.18,载药量为2.51%,包封率为79.19%,Zeta电位为-33.1 mV;体外释药规律符合Weibull方程lnln［1/(1-Q)］=0.263 3lnt+0.050 9（r＝0.948 5）;HCPT-SSLN 4 ℃下放置6个月,纳米粒外观、粒径及包封率无明显变化。结论：所制备的HCPT-SSLN包封率和载药量较高,粒径分布均匀,稳定性良好,体外释药具有缓释特点,为羟基喜树碱的临床应用提供了更广阔的前景。     

还原响应型甲氨蝶呤/羟基喜树碱纳米粒的制备及体外评价

目的 合成药物-聚合物偶联物透明质酸-二硫键-甲氨蝶呤-亚油酸(hyaluronic acid-disulfide bond-methotrexate- linoleic acid,HA-SS-MTX-LA),并以其为载体包载羟基喜树碱(hydroxycamptothecin,HCPT)制备纳米粒(nanoparticles,NPs)(HA-SS-MTX-LA@HCPT NPs),考察该NPs的体外释药行为及体外抗肿瘤活性。方法 在1-乙基-(3-二甲基氨基丙基)碳二亚胺盐酸盐、N-羟基琥珀酰亚胺的催化下,通过酰胺化反应合成药物-聚合物偶联物HA-SS-MTX-LA,并采用核磁共振氢谱、傅里叶变换红外光谱确证其化学结构。采用超声法制备HA-SS-MTX-LA NPs,以临界聚集浓度和粒径为指标,筛选获得LA和HA-SS-MTX的最佳投料比。以HCPT为模型药物,采用乳化溶剂挥发法包载药物,考察HA-SS- MTX-LA NPs的共载药性能。通过体外释放试验考察HA-SS-MTX-LA@HCPT NPs的还原响应性,采用MTT法考察其体外抗肿瘤活性。结果 成功制得HA-SS-MTX-LA NPs,LA和HA-SS-MTX的最佳摩尔投料比为1∶1,临界聚集浓度为60.50 mg×mL^-1,NPs粒径为(226.6±2.5)nm,PDI为0.180±0.036。HA-SS-MTX-LA@HCPT NPs的粒径为(257.59±1.41)nm,PDI为0.132±0.009,包封率为(72.46±0.73)%,载药量为(11.51±0.32)%。体外释放结果表明药物在高浓度谷胱甘肽条件下可快速释放,MTT试验结果表明HA-SS-MTX-LA@HCPT NPs对HepG2细胞和Bel-7402细胞生长具有显著的抑制作用。结论 制得的HA-SS-MTX-LA@HCPT NPs粒径均匀,包封率和载药量较高,具有良好的共载药性能、还原响应性和抗肿瘤活性,同时可进一步提高HCPT和MTX的体外抗肿瘤效果。     

羟基喜树碱脂质聚合物杂化纳米粒的制备及体内外性能评价

目的 以二硬脂酰基磷脂酰乙醇胺-聚乙二醇2000(1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000],DSPE-PEG2000),大豆卵磷脂(soy lecithin-100M,SL-100M),共聚...     

新型羟基喜树碱纳米粒形态的影响因素考察

目的 考察实验室制备的新型棒状羟基喜树碱纳米粒形态的影响因素。 方法 选择不同投料比、不同制备方法及是否存在其他稳定剂为考察因素,分别进行以新型树枝状大分子PAMAM-co-0.25OEG,PGD为稳定剂的羟基喜树碱纳米粒的制备,并观察纳米粒在电镜下的形态。 结果 以PGD为稳定剂的羟基喜树碱纳米粒在电镜下的形态不受制备方法的影响,但和药物与稳定剂的比例,即投料比有关,当投料比从4:1增加至1:3时,较多PGD稳定剂的存在更容易包裹药物形成球形纳米粒。Chol-PEG600稳定剂与PGD稳定剂同时存在时,高载药量的羟基喜树碱纳米粒中也会存在球形粒子。结论 羟基喜树碱纳米粒的形态与稳定剂的用量及其结构有关,且稳定剂性质不同,粒径大小相同的纳米粒电位也相差较大。     

多西紫杉醇白蛋白纳米粒的制备及体外评价

目的：制备多西紫杉醇白蛋白纳米粒，考察白蛋白和多西紫杉醇的处方量及乙醇加入量等因素对其形态、粒径、Zeta电位、收率、包封率、载药量和体外释药特性的影响，并对处方工艺进行优化。方法：采用去溶剂化-化学交联法制备多西紫杉醇白蛋白纳米粒，透射电镜观察纳米粒形态，马尔文激光粒度仪测定其粒径分布及Zeta电位，考马斯亮兰-酶标仪法测定纳米粒收率，HPLC法测定纳米粒包封率和载药量；以累积释药百分率为指标，通过方程拟合释药曲线，考察制剂的体外释药特性。处方优化采用星点设计-效应面优化法，应用SAS统计软件对数据进行处理。结果：优化处方制得的纳米粒为类球形，平均粒径65．3nm，Zeta电位-31．4mV，纳米粒收率95．0％，包封率74．3％，载药量4．65％，制剂24小时体外累积释药百分率为74．4％。结论：难溶性抗癌药物多西紫杉醇可以采用去溶剂化-化学交联法制备成白蛋白纳米粒，其粒径小，稳定性高，可显著提高多西紫杉醇在水相中的浓度。其优化处方中药物的释放显著慢于原料药磷酸盐缓冲溶液的释放，具有缓释效果。     

5-氟尿嘧啶纳米粒的制备及其体外释药的研究

目的以生物可降解材料乳酸/羟基乙酸共聚物(PLGA)制备5-氟尿嘧啶(5-FU)纳米粒,并考察纳米粒的体外释放特性。方法采用复乳-溶剂挥发法结合高压均质法制备5-Fu-PLGA纳米粒,用透射电镜观察纳米粒的形态,并研究了5-Fu纳米粒的粒径、载药量、包封率和体外释药。结果5-FU-PLGA纳米粒为圆整的类球形实体粒子,平均粒径为85.4nm,载药量为12.4%±0.7%,包封率为64.1%±5.3%,体外释药符合H iguch i方程:Q=0.0585t1/2 0.087(r=0.9923)。结论所制5-FU纳米粒具有明显的缓释作用。     

曲尼司特的壳聚糖纳米粒的制备和体外释放研究

目的：制备载有曲尼司特的壳聚糖纳米粒,考察它的性质和体外释放。方法：用多聚磷酸钠（TPP—Na）做交联剂,采用离子交联法制备的曲尼司特壳聚糖纳米粒。测定纳米粒的大小和电位,并考察纳米粒溶液的稳定性和纳米粒的体外释放。结果：制备了粒径为285．5nm的米粒,而且多分散指数为0．04,药物的包封率为82.4％。结论：壳聚糖可用作制备曲尼司特纳米粒的载体,制备的载药纳米粒有可能开发成注射剂。     

N-琥珀酰壳聚糖纳米粒的制备及体外评价

目的制备N-琥珀酰壳聚糖纳米粒并对其进行体外评价。方法采用乳化溶剂挥发法制备N-琥珀酰壳聚糖纳米粒;以包封率、载药量及粒径为指标,采用正交设计法对处方进行优化;考察其理化特征及体外释药行为。结果纳米粒包封率及载药量分别为62.36%和18.98%,平均粒径及zeta电位分别为(206.6±64.7)nm和(-27.2±0.2)mV;1 h药物释放达到45%,随后药物的释药行为是一个缓释过程。结论作者采用乳化溶剂挥发法成功制得N-琥珀酰壳聚糖纳米粒。该方法制得纳米粒包封率较高,制备工艺简单。     

羟基喜树碱脂质体的制备及质量评价研究

目的:制备羟基喜树碱(HCPT)脂质体,并对其质量进行评价.方法:采用薄膜分散-高压乳匀法制备羟基喜树碱脂质体;用激光粒度分析仪测定其Zeta电位、粒径大小;考察其在0.9%NaCl溶液、水、5%葡萄糖溶液中8 h的稳定性;用凝胶柱层析法考察包封率;采用薄膜透析法考察体外释药性质.结果:羟基喜树碱脂质体Zeta电位为(-33.1±1.3) mV,平均粒径(182.5±5.6) nm,8 h内在水、5%葡萄糖溶液中稳定性良好;包封率(91.2±1.2)%;体外释药曲线符合Higuchi方程Q=1.291 6t1/2 0.309 8,r=0.980 3.结论:本试验制备的羟基喜树碱脂质体稳定性好,大小均匀, 包封率高,并具有延缓药物释放的性质.     

Preparation and in vitro evaluation of thienorphine-loaded PLGA nanoparticles

Poly (d,l-lactic-co-glycolide) nanoparticles (PLGA-NPs) have attracted considerable interest as new delivery vehicles for small molecules, with the potential to overcome issue such as poor drug solubility and cell permeability. However, their negative surface charge decreases bioavailability under oral administration. Recently, cationically modified PLGA-NPs has been introduced as novel carriers for oral delivery. In this study, our aim was to introduce and evaluate the physiochemical characteristics and bioadhesion of positively charged chitosan-coated PLGA-NPs (CS-PLGA-NPs), using thienorphine as a model drug. These results indicated that both CS-PLGA-NPs and PLGA-NPs had a narrow size distribution, averaging less than 130?nm. CS-PLGA-NPs was positively charged (+42.1?±?0.4?mV), exhibiting the cationic nature of chitosan, whereas PLGA-NPs showed a negative surface charge (?2.01?±?0.3?mV). CS-PLGA-NPs exhibited stronger bioadhesive potency than PLGA-NPs. Furthermore, the transport of thienorphine-CS-PLGA-NPs by Caco-2 cells was higher than thienorphine-PLGA-NPs or thienorphine solution. CS-PLGA-NPs were also found to significantly enhance cellular uptake compared with PLGA-NPs on Caco-2 cells. An evaluation of cytotoxicity showed no increase in toxicity in either kind of nanoparticles during the formulation process. The study proves that CS-PLGA-NPs can be used as a vector in oral drug delivery systems for thienorphine due to its positive surface charge and bioadhesive properties.     

Preparation and in vitro evaluation of heparin-loaded polymeric nanoparticles

Nanoparticles of a highly soluble macromolecular drug, heparin, were formulated with two biodegradable polymers (poly-E-caprolactone [PCL] and poly (D, L-lactic-co-glycolic-acid) 50/50 [PLAGA]) and two nonbiodegradable positively charged polymers (Eudragit RS and RL) by the double emulsion and solvent evaporation method, using a high-pressure homogenization device. The encapsulation efficiency and heparin release profiles were studied as a function of the type of polymers employed (alone or in combination) and the concentration of heparin. Optimal encapsulation efficiency was observed when 5000 IU of heparin were incorporated in the first emulsion. High drug entrapment efficiency was observed in both Eudragit RS and RL nanoparticles (60% and 98%, respectively), compared with PLAGA and PCL nanoparticles (<14%). The use of the two types of Eudragit in combination with PCL and PLAGA increased the encapsulation efficiency compared with these two biodegradable polymers used alone; however, the in vitro drug release was not modified and remained low. On the other hand, the addition of esterase to the dissolution medium resulted in a significant increase in heparin release. The in vitro biological activity of released heparin, evaluated by measuring the anti-Xa activity by a colorimetric assay, was conserved after the encapsulation process.     

Preparation of E-selectin-targeting nanoparticles and preliminary in vitro evaluation

Targeted delivery aims to concentrate therapeutic agents at their site of action and thereby enhance treatment and limit side-effects. E-selectin on endothelial cells is markedly up-regulated by cytokine stimulation of inflamed and some tumoral tissues, promoting the adhesion of leukocytes and metastatic tumor cells, thus making it an interesting molecular target for drug delivery systems. We report here the preparation of targeted nanoparticles from original amphiphilic block copolymers functionalized with an analog of sialyl Lewis X (SLEx), the physiological ligand of E-selectin. Nanoparticles, prepared by nanoprecipitation, caused no significant cytotoxicity. Ligand-functionalized nanoparticles were specifically recognized and internalized better by tumor necrosis factor α (TNF-α)-activated human umbilical vein endothelial cells (HUVECs) than control nanoparticles or HUVECs with low E-selectin expression. These nanoparticles are designed to carry the ligand at the end of a PEG spacer to improve accessibility. This system has potential for the treatment of inflammation, inhibition of tumor metastasis, and for molecular imaging.     

Preparation and in vitro evaluation of bFGF-loaded chitosan nanoparticles

The objective of our study was to prepare and characterize basic fibroblast growth factor (bFGF)-loaded nanoparticles. Protein-loaded chitosan nanoparticles were obtained by ionotropic gelation process based on the interaction between chitosan and tripolyphosphate (TPP). The protein-loading capacity and encapsulation efficiency were 0.021% and 27.388%, respectively. The bFGF-loaded nanoparticles have a mean diameter of 424 nm, a narrow size distribution, spherical shape and positive surface charges. In vitro release showed that the extent of release was 68% at 24 hr. The protein integrity was investigated by SDS-PAGE analysis that confirmed protein integrity was not affected by the encapsulation procedure and release conditions.     

HPLC法测定羟基喜树碱人血清白蛋白纳米粒中的药物含量

目的建立羟基喜树碱(10-hydroxycamptothecin,HCPT)人血清白蛋白纳米粒(human serum al-bumin nanoparticle,HSA-NP)中药物含量的测定方法。方法采用Kromasil C18色谱柱(250 mm×4.6 mm,5μm),流动相为甲醇-水(体积比45∶55),流速1.0 mL.min-1,紫外检测波长266 nm,柱温35℃。结果在本实验条件下制剂中辅料对HCPT含量的测定无干扰,HCPT质量浓度在2.0~10.0 mg.L-1内线性关系良好(r=0.999 9,n=5),HCPT平均加样回收率为100.2%,RSD为1.0%(n=9)。结论本法准确可靠、简便易行,可用于羟基喜树碱人血清白蛋白纳米粒(HCPT-HSA-NP)中药物含量的测定。     

盐酸伊立替康纳米粒的制备及体外评价

目的:制备盐酸伊立替康纳米粒,并对其纳米粒形态、粒径、包封率和释放进行评价。方法:采用沉淀法制备盐酸伊立替康纳米粒,以包封率作为考察指标,筛选最优处方。用透射电镜观察纳米粒形态,激光粒径测定仪测定粒径,凝胶过滤法测定药物的包封率,透析法考察体外释药特质。结果:盐酸伊立替康纳米粒形态规整,几呈球形,强度径为(193.5±2.5)nm,载药量为26.35%,包封率为(98.00±0.01)%,体外24h的累积释放率为62.09%,比水溶液释放慢。结论:通过优化处方和工艺,制备出的盐酸伊立替康纳米粒粒径均匀,包封率较高,体外释药具有缓释特点。     

Synthesis and preliminary anticancer evaluation of 10-hydroxycamptothecin analogs

We have synthesized new 10-hydroxycamptothecin (HCPT) analogs and evaluated their anticancer activity in cell culture and in experimental animal tumor model. Although the new analogs were less potent against L1210 leukemia cells in vitro, some of them were more efficacious against L1210 leukemia in vivo compared to the parent HCPT.     

川芎嗪固体脂质纳米粒的制备及质量评价

目的制备川芎嗪固体脂质纳米粒并对其制剂性质进行评价。方法采用热熔乳化-高压均质技术制备川芎嗪固体脂质纳米粒,同时利用Box-Behnken效应面法优化其制剂处方,并通过微观形态、粒径分布、多聚分散系数(polydispersity index,Pd I)和Zeta电位、体外释药行为对川芎嗪固体脂质纳米粒的性质进行了评价。结果川芎嗪固体脂质纳米粒的最优处方构成:单硬脂酸甘油酯质量浓度为55 g·L~(-1)、大豆卵磷脂质量浓度为45 g·L~(-1)、脂药质量比为35∶1,制备的川芎嗪固体脂质纳米粒外观澄清透明、略带乳光状;透射电镜照片显示纳米粒大小均一,呈球形或类球形分布,测得平均粒径为(127.4±31.6)nm,Pd I为0.238,Zeta电位为(-11.5±0.9)m V;川芎嗪固体脂质纳米粒在12 h内累积释放度为95.3%。结论该处方可用于川芎嗪固体脂质纳米粒的制备,工艺简单易行,稳定可行。