改良自乳化溶剂扩散法制备MePEG-PLA纳米粒对成骨细胞的毒性

背景：两亲性嵌段聚合物由于其较强的载药能力强、纳米级大小、血液中长循环等优点在载药系统中得到广泛的应用。目的：评估改良自乳化溶剂扩散法制备的甲氧基封端的聚乙二醇-聚乳酸（MePEG-PLA）纳米粒对人骨肉瘤细胞MG63的毒性。方法：通过改良自乳化溶剂扩散法制备MePEG-PLA纳米粒,MTS法测定纳米粒培养1,2,3d后对MG63的毒性。激光粒度分析仪测定纳米颗粒的粒径大小、粒径分布及Zeta电位;透射电镜表征纳米胶束外观形态;酶标仪检测培养1,2,3d细胞吸光度值。结果与结论：MePEG-PLA纳米粒的平均粒径为25.7nm,分布均匀,呈球形,Zeta电位为-8.06mV,MePEG-PLA毒性为0级。提示改良自乳化溶剂扩散法制备纳米粒简单易行,制备的纳米粒无毒,具有良好的应用前景。     

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.     

盐酸表阿霉素纳米靶向制剂的缓释效应***◆

背景:盐酸表阿霉素是一种广谱抗生素,目前临床使用的不足多为药物释放快、目标组织药物浓度低,静脉给药后广泛分布于体内各种组织器官,不良反应明显.目的:针对盐酸表阿霉素临床应用的不足,制备盐酸表阿霉素纳米靶向注射制剂.方法:以叶酸偶联牛血清白蛋白为载体,采用乳化-高压匀质法,制备盐酸表阿霉素纳米靶向注射制剂,以激光粒度分析仪测定纳米颗粒的粒径大小、粒径分布及 Zeta 电位,扫描电镜观察纳米颗粒的表面形态,高效液相色谱法分析白蛋白负载盐酸表阿霉素纳米制剂的包封率、载药量和释药性能.结果与结论:制备的盐酸表阿霉素纳米粒外观呈均匀球型,粒径分布较窄,平均粒径为(157.73±0.40) nm,平均 Zeta 电位为(-30.85±0.43) mV,载药量22.78%,包封率可达96.24%.体外模拟释药结果表明药物释放曲线分为两个阶段,突释阶段微球释药量在24 h内达42.6%,缓释阶段纳米粒释药持续时间长,在112 h 时释药量达84.1%,载药纳米粒的药物释放速率持续稳定.结果表明乳化结合高压匀质法制备的盐酸表阿霉素纳米靶向制剂粒径均匀,粒径范围分布窄,载药量和包封率高,具有一定的缓释作用.     

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。     

正交优化聚乳酸-羟基乙酸纳米粒的制备

背景:聚乳酸-羟基乙酸纳米粒或纳米微球用于制备生物降解型缓释或定向给药体系已经研究了近30年,是国内外研究的热点.该体系能够控制粒径大小、延缓药物降解、延长药物释放时间、靶向释放、降低药物毒性和刺激性等.目的:以紫杉醇为模型药物、聚乳酸-羟基乙酸为包裹材料,探索载药纳米粒的制备条件对粒径、包封率等的影响,确定最佳制备工艺条件.方法:采用乳化-溶剂挥发法制备聚乳酸-羟基乙酸纳米粒,以粒径、包封率和载药量等为观察指标,通过正交设计法优化纳米粒制备工艺条件.结果与结论:通过正交实验设计,优化了制备工艺条件,其最佳条件是超声乳化时间为15 min,乳化剂浓度为1%,油水相比为1:25,合成温度为25℃.在此条件下进行实验,制备出的载药纳米粒粒径为217.6 nm,载药量1.79%,包封率85%.该制备工艺简单、稳定,优化制备条件,可制备出包封率高、粒径适宜的紫杉醇-聚乳酸-羟基乙酸纳米粒.     

聚氰基丙烯酸正丁酯纳米颗粒的表面修饰和转染

背景:聚氰基丙烯酸烷基酯在人体内极易生物降解,且对许多组织具有生物相容性,近年来一直受到国内外医药界的广泛关注.目的:比较不同表面修饰的聚氰基丙烯酸正丁酯纳米颗粒的物理化学性质,并考察它们体外基因转染活性.设计、时间及地点:对比观察实验,于2007-09/12在中南大学卫生部纳米生物技术重点实验室完成.材料:采用乳化聚合的方法制备表面分别修饰壳聚糖、葡聚糖和氨基化的聚乙二醇的聚氰基丙烯酸正,‘酯纳米颗粒.方法:透射电镜观察粒径大小、纳米粒形态;Zetasizer Nano system电位分析仪测定Zeta电位;MTT法检测纳米粒的细胞毒性;用流式细胞仪考察纳米粒的体外转染效率.主要观察指标:纳米粒的表面电位、粒径、细胞毒性及其转染效率.结果:成功制备了粒径约200 nm左右,表面电位分别为25.53,-17.42和0.293 5 mV的壳聚糖、葡聚糖和氨基化的聚乙二醇修饰的聚氰基丙烯酸正丁酯纳米颗粒,且0.1 g/L的质量浓度对HepG2细胞无明显毒性,带正电的壳聚糖修饰的聚氰基丙烯酸正丁酯纳米颗粒的转染效率明显高于葡聚糖和氨基化的聚乙二醇修饰的纳米粒.结论:聚氰基丙烯酸正丁酯纳米颗粒经表面修饰不同物质后可以带上正电、负电及中性电荷,而壳聚糖修饰的纳米粒能有效地将基因递送到细胞内,并且报告基因能在细胞内表达.因此,可用做基因递送的载体.     

鬼臼毒素纳米脂质载体的制备及质量考察

目的:纳米脂质载体是近年来继固体脂质纳米粒发展起来的第2代亚微粒载药系统,具有较高的载药量和物理稳定性.探讨鬼臼毒素-脂质纳米粒(podophyllotoxin-loaded nanostructured lipid carrier,PPT-NLC)的制备方法及理化性质.方法:实验于2006-08/2007-10在南方医科大学药学部实验室完成.选择固体脂质硬脂酸、单硬脂酸甘油脂和液态脂质油酸,采用改良的乳化蒸发-低温固化法制备PPT-NLC,用同法制备不含油酸的PPT-固体脂质纳米粒(Solid lipid nanoparticles,SLN)纳米粒混悬液.用透射电镜、Zeta电位仪、高效液相色谱法、pH计考察PPT-NLC理化性质,并比较SLN与NLC的包封率和稳定性.结果:透射电镜下PPT-NLC外形呈圆形或椭圆形,平均粒径为(88.2±8.4)nm,多分散指数为0.190±0.085,Zeta电位为(-33.2±3.1)mV,包封率为86.6%.PPT-SLN分别为(75.3±16.2)nm,0.300±0.072,(-25.2±3.4)mV,包封率为76.5%.结论:PPT-NLC制备工艺简单,分布均匀,稳定性较SLN好,包封率高.     

两亲性壳聚糖衍生物负载及缓释醋酸曲安奈德的性能

背景:醋酸曲安奈德是一种长效肾上腺糖皮质激素,具有较强的抗炎作用.近年来在眼内疾病的治疗中取得了较好的效果,但同时带来一些不良反应,且需多次注射,以防止疾病复发.壳聚糖经接枝改性,生成的共聚物可在水溶液中生成纳米粒,用于药物的缓释载体,延长药物作用时间,降低不良反应,提高生物利用度.目的:合成含脱氧胆酸基团的两亲性壳聚糖衍生物作为醋酸曲安奈德的载体材料,制备具有缓释功能的载药纳米胶束,研究其负载和缓释醋酸曲安奈德的性能.方法:通过酰胺化反应在壳聚糖上偶联脱氧胆酸基团,合成两亲性壳聚糖衍生物.透射电镜观察纳米粒的外观形态和粒径,Zeta电位分析仪测定纳米粒的Zeta电位,体外释放实验检测负载醋酸曲安奈德的壳聚糖-脱氧胆酸纳米粒的包封率、载药量和体外释药性能.结果与结论:合成出含脱氧胆酸基团的两亲性壳聚糖衍生物,它能与醋酸曲安奈德形成载药纳米胶束,载药量可高达82%.随着载药量的增加,载药纳米胶束的粒径逐渐增大,而Zeta电位则呈下降的趋势.体外释放的结果表明载药纳米胶束能起到72h缓释醋酸曲安奈德的作用.提示以两亲性壳聚糖衍生物为载体的载药纳米胶束显示出较好的缓释醋酸曲安奈德性能,将有希望提高醋酸曲安奈德的治疗效果.     

构建新型液态氟碳壳聚糖纳米超声造影微粒

目的 构建一种新型天然高分子聚合物纳米超声造影微粒,表征其理化特征、体外显像效果及其对肿瘤细胞的结合能力和毒性。 方法 采用超声乳化法制备包裹液态氟碳PFOB的壳聚糖(CTS)纳米粒和FITC标记的壳聚糖纳米粒(FITC-CTS),表征其表面形态、粒径、Zeta电位和稳定性;评价纳米粒的体外超声显像效果,以激光共聚焦观察FITC-CTS与细胞的结合作用,流式细胞仪检测FITC-CTS对细胞的黏附比例。 结果 制备的纳米粒形态圆整,CTS纳米粒平均粒径为(248.52±7.96)nm,Zeta电位为+(29.91±0.64)mV,FITC-CTS纳米粒平均粒径为(244.83±2.72)nm,Zeta电位为+(22.21±0.53)mV。纳米粒性质稳定,在体外能增强超声显影,激光共聚焦观察到纳米粒聚集在细胞膜周围,流式细胞仪测得纳米粒对细胞的黏附比例为(45.15±8.35)%。 结论 构建的CTS纳米粒性质稳定,体外能与肿瘤细胞MCF-7紧密结合,增强超声回声。     

[通讯作者] 游玉峰,主任医师,恩施土家族苗族自治州中心医院放射科,445000,E-mail: yyfeng1977@163.com。

目的 制备载10-羟基喜树碱(10-hydroxycamptothecin, 10-HCPT)液态氟碳靶向纳米粒,观察其对人卵巢癌SKOV-3细胞的寻靶能力及体外超声/CT双模态成像效果。方法 以羟基端乳酸/羟基乙酸共聚物(PLGA-COOH)、全氟溴辛烷(perflurooctyl bromide,PFOB)和10-HCPT为原料,采用成熟的双乳化法制备PLGA@-HCPT-PFOB纳米粒,采用光学显微镜、扫描电镜以及透射电镜观察其外部形态以及内部结构;马尔文粒径分析仪测量其粒径大小及表面电位;紫外分光光度测定10-HCPT的包封率和载药量;通过碳二亚胺法连接cRGD肽制备cRGD-PLGA@10-HCPT-PFOB靶向纳米粒,用激光共聚焦显微镜检测PLGA@10-HCPT-PFOB与cRGD肽的连接情况,在体外实验检测其对卵巢癌SKOV-3细胞的靶向性能;观察靶向纳米粒的体外超声成像和CT成像能力。结果 所制得的靶向载药纳米微球为黄色混悬液,光镜下纳米粒大小、分布均匀,马尔文粒径分析仪测量其平均粒径为(322.03±5.34)nm,Zeta电位为(-1.55±0.10)mV;扫描电镜显示该靶向纳米粒呈球形、表面光滑,透射电镜示其为核壳结构,PLGA包裹PFOB和10-HCPT,其10-HCPT包封率和载药量分别为(81.34±2.28)%和(13.24±1.24)%;激光共聚焦显微镜观察到标记FITC的cRGD肽显示为绿色,与标记DiI的红色纳米粒共同融合成橙黄色;激光共聚焦显微镜及流式细胞仪显示大量纳米粒靶向到细胞表面,与细胞膜上的ανβ3受体结合,部分被SKOV-3细胞吞噬;随着靶向纳米粒的浓度不断增加,其体外超声及CT成像明显增强。结论 成功制备载10-HCPT液态氟碳靶向纳米粒,该纳米粒10-HCPT包封率、载药量较高,对卵巢癌SKOV-3细胞有较强的靶向性,通过聚集显影,可增强体外超声及CT成像。     

Utilization of poly(DL-lactide-co-glycolide) nanoparticles for preparation of mini-depot tablets by direct compression.

PURPOSE: The objectives of this study were to prepare the long-acting matrix tablets by direct compression of the mixture of drug and poly(DL-lactide-co-glycolide) (PLGA) nanoparticles and to clarify the effects of such factors as polymer species, mixing ratio of nanoparticles with different molecular weights, and the tablet weight on the drug release and to discuss the mechanism of drug release from matrix tablets. In addition, mini-matrix tablets were prepared to investigate the possibility of application as an implantable dosage form. METHODS: PLGA nanoparticles were prepared by the modified spontaneous emulsion solvent diffusion method. The matrix tablets were prepared by direct compression of mixtures of drug and nanoparticles, and then the release properties, swelling properties and changes in molecular weight of PLGA during the release test were evaluated. RESULTS: The drug showed the biphasic release patterns from all matrix tablets; i.e. a portion of the drug was released rapidly (the initial release phase), the release stopped for a long period (the lag time), and then the residual drug was released (the second release phase). Matrix tablets with various biphasic release patterns could be prepared by altering the molecular weight or copolymer ratio of PLGA. The addition of nanoparticles of low molecular weight PLGA to those of high molecular weight reduced the release rate at the initial release phase, but that at the second release phase was almost entirely unaffected by mixing ratio. Also, the release patterns could be changed by altering the tablet weight and size, but the amounts released per unit of surface area were the same. Hydration analysis suggested that the initial release rates were correlated well with the swelling properties of tablets. CONCLUSION: This system had advantages in terms of simplicity in design and predictability of drug release rate and may be useful as an implantable dosage form.     

纳米磷酸钙对MG63细胞生物学行为的影响

背景:纳米材料的尺寸、形貌、结晶度等性质对其毒性具有明显的影响。目的:选用3种不同形貌的磷酸钙纳米颗粒来探索材料形貌对MG63细胞各种生物学行为的影响,并分析其物理化学性质与生物学效应之间的关系。方法:利用水热法和化学沉淀法制备球形、梭形和棒状3种不同形貌的磷酸钙颗粒并铺膜,通过透射电镜、场发射扫描电镜、原子力显微镜、动态光散射、X射线衍射对磷酸钙颗粒及其膜的尺寸、形貌、粗糙度和结晶度等性质进行表征。在磷酸钙膜上培养MG63细胞,检测磷酸钙对细胞的黏附、增殖、分化及凋亡的影响。结果与结论:磷酸钙形貌及结晶度对MG63细胞的增殖具有明显的影响。颗粒长径比大,结晶度高的颗粒,能促进细胞的增殖;反之,则抑制细胞的增殖。磷酸钙膜的粗糙度对细胞的黏附过程具有明显的影响,粗糙度越大,抑制作用越明显。3种磷酸钙对细胞的分化和凋亡没有明显的影响。     

羟基磷灰石纳米颗粒对骨肉瘤MG63抑制作用的体外实验研究

目的探讨羟基磷灰石（Hydroxyapatite,HAP）纳米颗粒对骨肉瘤MG63的作用及相关机制。方法 MTT法观察不同浓度HAP纳米颗粒对MG63的抑制作用,测定HAP纳米粒子对MG63的时效曲线,丫啶橙/溴化已啶细胞荧光染色及流式细胞术检测HAP纳米颗粒对MG63细胞凋亡的影响。结果 MTT法检测发现HAP纳米颗粒浓度在10-400 mg/L范围内,随着浓度的增高HAP纳米颗粒对MG63的抑制作用在72 h内逐渐增强,以后逐渐达到平台期。形态学观察和流式细胞术检测可见HAP纳米粒子有诱导细胞凋亡的趋势,实验组和对照组的细胞凋亡率（%）分别为19.03±5.80和12.32±3.84,两组间差别显著（P〈0.05）;实验组G0/G1期细胞明显多于对照组,而S期细胞明显少于对照组,两组间差别显著（P〈0.05）。结论 HAP纳米颗粒可以诱导肿瘤细胞凋亡,对骨肉瘤MG63有明显的抑制作用。     

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。     

Development of a biodegradable nanoparticle platform for sildenafil: formulation optimization by factorial design analysis combined with application of charge-modified branched polyesters

Biodegradable nanoparticles have gained tremendous attraction as carriers for controlled drug delivery to the lung. Despite numerous advances in the field, e.g. development of suitable methods for pulmonary administration of polymeric nanoparticles, a sufficient association of the therapeutic agent with the carrier system as well as drug release in a controlled fashion remain considerable challenges. Hence, this study examines the optimization of biodegradable sildenafil-loaded nanoparticle formulations intended for aerosol treatment of pulmonary hypertension. A factorial design analysis was employed to identify the important experimental factors involved in the preparation of nanoparticles by the solvent evaporation technique. The effect of tailored charge-modified branched polyesters on drug loading and in vitro drug release from nanoparticles was also evaluated. Moreover, colloidal stability of obtained nanoparticles was assessed, and stabilization of nanoparticles by lyophilization was accomplished without additional excipients. Essential experimental factors were identified and optimized to allow the preparation of nanoparticles composed of linear polyesters with a sildenafil content of ~5 wt.%. The in vitro drug release profile from these nanoparticles demonstrated a sustained release of sildenafil over ~90 min. Application of charge-modified branched polyesters enhanced the drug content in nanoparticles and drug release profile, according to the charge-density present in the employed polymer. Accordingly an increase in drug loading by a factor of ~1.4, a prolonged drug release profile from nanoparticles over ~240 min was achieved. Sildenafil release from nanoparticles made of linear and charge-modified branched polyesters was governed by a diffusion process. The obtained drug diffusion coefficients were decreased as the charge-density present in the applied polymer was increased, which promotes the strategy to improve drug loading and release rates by electrostatic interactions between polymer and drug. In addition, nanoparticles showed high colloidal stability in different media of importance for pulmonary application and were successfully stabilized by lyophilization. In conclusion, optimization of the nanoparticle preparation process together with the application of tailored polymeric materials facilitated the synthesis of promising drug carriers for sildenafil that permit a novel treatment modality for severe pulmonary hypertension.     

MG63和MG63/ADR骨肉瘤裸鼠模型血管内皮生长因子和核因子κB1的表达

背景:恶性肿瘤耐药研究中发现核因子κB1及血管内皮生长因子基因可能与肿瘤耐药密切相关。目的:观察MG63和MG63/ADR骨肉瘤裸鼠模型中血管内皮生长因子和核因子κB1表达的差异。方法:对数期生长的MG63细胞采用阿霉素浓度递增培养法冲击诱导建立MG63/ADR细胞株。BALB/C裸鼠随机分为2组,分别将含5.0×106个MG63和MG63/ADR细胞的0.2mL细胞悬液采用皮下接种法注入裸鼠的一侧腋部皮下。第6周处死裸鼠取材。结果与结论:注射MG63和MG63/ADR细胞的2组裸鼠成瘤率均为100%;免疫组织化学及RT-PCR方法检测发现MG63/ADR组瘤灶中血管内皮生长因子和核因子κB1基因和蛋白的表达均明显高于MG63组(P<0.05)。说明血管内皮生长因子和核因子κB1表达的上调可能是导致骨肉瘤耐药的重要原因。     

W/O/W double emulsion technique using ethyl acetate as organic solvent: effects of its diffusion rate on the characteristics of microparticles.

Monomethoxypoly(ethylene glycol)-b-poly(DL-lactide) copolymer (PELA) microparticles loading lysozyme were prepared through a modified W/O/W double emulsion-solvent diffusion method using ethyl acetate (EA) as organic solvent. The modified process was divided into five steps: (1) primary emulsification (W1/O), (2) re-emulsification (W1/O/W2), (3) pre-solidification, (4) solidification and (5) purification. The pre-solidification step was carried out in the modified process to control the diffusion rate of EA from oil phase into outer aqueous phase, in order to prevent the wall polymer from precipitation, which usually occurred when the diffusion rate was too fast. The adequately rapid solidification of microparticle caused by controlled fast diffusion of EA and the use of amphiphilic copolymer PELA as wall material, facilitated a high protein entrapment (always above 94%) and full preservation of bioactivity of entrapped lysozyme. It was found that the volume of the outer aqueous phase in the re-emulsification step and the shear stress in the pre-solidification step had a significant effect on the diffusion rate of EA from the droplets into outer aqueous solution, and thereby on the characteristics of the resultant microparticles. With the volume or the shear stress increasing, the removal rate of EA increased, resulting in rapid solidification of the microparticles. This result led to a lower burst effect and a slower lysozyme release from the microparticles. This study suggests that the modified W/O/W double emulsion-solvent diffusion method with EA as organic solvent is a prospective technique to prepare biodegradable microparticles containing water-soluble sensitive agents.     

Stealth PEGylated polycyanoacrylate nanoparticles for intravenous administration and splenic targeting.

The aim of the present work was to investigate the biodistribution characteristics of PEG-coated polycyanoacrylate nanoparticles prepared by the nanoprecipitation/solvent diffusion method using the previously synthesized poly(MePEGcyanoacrylate-hexadecylcyanoacrylate) copolymer. It was observed that [14C]-radiolabeled PEGylated nanoparticles remained for a longer time in the blood circulation after intravenous administration to mice, compared to the non-PEGylated poly(hexadecylcyanoacrylate) (PHDCA) nanoparticles. Furthermore, hepatic accumulation was dramatically reduced, whereas a highly increased spleen uptake was shown. The PEGylation degree of the polymer seemed not to affect the in vivo behavior of the nanoparticles, whereas previously obtained in vitro data have shown a modification of plasma protein adsorption depending on the density of PEG at the surface of the particles. Moreover, the study of the in vitro cytotoxicity of the nanoparticles revealed that the PEGylation of the cyanoacrylate polymer reduced its toxicity. These results open up interesting perspectives for the targeting of drugs to other tissues than the liver.