Preparation and Evaluation of MPEG-PCL Polymeric Nanoparticles Against Gastric Cancer

This paper provides a new treatment for gastric cancer with a new OMT delivery system.We synthesized MPEG-PCL,an amphiphilic polymer,to construct a nanoparticle encapsulated OMT by pH gradient method,and then examined the nanodrug’s therapeutic efficacy.An integral analytical method was used to characterize the structure of MPEG-PCL.The single factor method and orthogonal test were utilized to investigate the optimum preparation process.The morphology and average size of the OMT-NPs were analyzed by transmission electron microscopy and Zetasizer.CCK-8 assay and confocal fluorescent microscope were used to study the inhibitory effect on SGC-7901 gastric cancer cells.The average size of nanoparticles was 95.86±1.54 nm.The maximum encapsulation efficiency of OMT was 46.84±4.37%,while the drug loading content was 8.89±1.09%.The cumulative release of nanoparticles was 73.07±1.5%,inspected through dynamic dialysis in vitro.Compared with free OMT,OMT-NPs showed enhanced cytotoxic effects in SGC-7901 cells.The nanoparticles could efficiently deliver the OMT into the cancer cells and release it.The OMT delivery system prepared in this paper provides a potential platform for the treatment of gastric cancer..

紫杉醇MPEG-PCL纳米粒的制备、表征及其体外释药行为研究

目的以聚乙二醇单甲醚-聚己内酯(MPEG-PCL)为载体制备紫杉醇MPEG-PCL纳米粒并对其体外释放行为进行考察。方法采用开环聚合法合成MPEG-PCL共聚物,采用核磁共振波谱仪(1H-NMR)、傅里叶红外光谱仪(FTIR)对其进行表征;通过共沉淀法制备了紫杉醇MPEG-PCL纳米粒,并测定了粒径分布、Zeta电位、结构特征、包封率以及载药量;同时以磷酸盐缓冲溶液(pH=7.4)为释放介质考察其体外释放行为。结果成功合成了相对分子质量为4 875的MPEG-PCL共聚物。透射电镜结果显示紫杉醇MPEG-PCL纳米粒具有规则的球形结构,纳米粒的平均粒径为(102.3±3.5)nm,PDI=0.102,药物包封率和载药量分别为(95.6±3.2)%和(8.5±0.4)%。体外释放结果显示紫杉醇可以缓慢的从MPEG-PCL纳米粒中释放出来。结论 MPEG-PCL共聚物是紫杉醇的良好载体,所制备的纳米粒具有包封率和载药量高、药物释放缓慢的特点。

Near-infrared responsive 5-fluorouracil and indocyanine green loaded MPEG-PCL nanoparticle integrated with dissolvable microneedle for skin cancer therapy

The prevalence of skin cancer is rising along with the rapid population aging in recent years.Traditional therapies,such as surgical treatment,radiotherapy,chemotherapy,photodynamic therapy,and immunotherapy,may accompany serious side effects,limiting their clinical benefits.According to the biological characteristics of skin cancer,we have already established two kinds of synergetic systems of photothermal therapy(microneedle)and chemotherapy,containing gold nanorods(GNR).Although the microneedle system exhibited great potential for skin cancer treatment,the system could be still improved further.So,we designed a near-infrared lightresponsive 5-fluorouracil(5-Fu)and indocyanine green(ICG)loaded monomethoxy-poly(ethylene glycol)-polycaprolactone(MPEG-PCL)nanoparticle(5-Fu-ICG-MPEG-PCL),and then 5-Fu-ICG-MPEG-PCL was integrated with a hyaluronic acid dissolvable microneedle system(HA MN)to get 5-Fu-ICG-MPEG-PCL loaded HA MN for treating skin cancers,including human epidermoid cancer and melanoma.In this system,hyaluronic acid,the microneedle carrier,possesses good skin penetration ability and is approved by FDA as a pharmaceutical adjuvant;5-Fu is recommended by FDA for skin cancer treatment;ICG,a photothermal agent,possesses a strong photothermal ability and is approved by FDA for its use in the human body.We hypothesized that 5-Fu-ICG-MPEG-PCL could be delivered by the dissolvable microneedle through the skin,and the release behavior of the drug in the nanoparticle could be controlled by near-infrared light for achieving a single-dose cure of skin cancer,improving the cure rate of skin cancer and providing a new idea and possibility for the clinical treatment of skin cancer.

正交试验优化葛根素聚合物胶束的制备工艺

目的正交试验设计优化葛根素聚合物胶束的制备工艺。方法以mPEG-PCL为载体材料,采用薄膜分散法制备葛根素聚合物胶束;以包封率为评价指标,经L_9(3~4)正交试验设计优化,确定胶束的最佳工艺。结果薄膜分散法制备聚合物胶束的最佳工艺为聚合物与药物比例100∶1,水相体积25 ml,水化温度50℃。三批样品平均包封率为(35.5±2.12)%。结论采用薄膜分散法制得胶束工艺可行,成型性好,粒径均匀。

姜黄素mPEG_(114)-PCL_(36)纳米胶束的制备及体外释药考察

目的:制备载姜黄素mPEG114-PCL36纳米胶束并考察其体外释药情况。方法:利用开环聚合法合成聚乙二醇单甲醚-聚己内酯(mPEG114-PCL36)嵌段共聚物,通过FT-IR和1H-NMR确证其结构,芘荧光探针法测定其临界胶束浓度。采用透析法制备姜黄素聚合物胶束,通过正交试验考察共聚物质量浓度、姜黄素质量浓度、水相与有机相的体积比对包封率、载药率和胶束粒径的影响。利用HPLC测定载药率、包封率,激光散射法测定粒径,动态透析法考察体外释药特性。结果:制备的纳米胶束平均粒径(48.5±1.7)nm,粒径多分散系数(0.20±0.07),包封率(49.12±1.26)%,载药率(4.46±0.12)%,72 h体外累计释放率41.9%,无明显突释现象。结论:透析法制备的姜黄素mPEG-PCL纳米胶束粒径小且分布均匀,具有良好的缓释性能。

The long-circulating effect of pegylated nanoparticles revisited via simultaneous monitoring of both the drug payloads and nanocarriers

The long-circulating effect is revisited by simultaneous monitoring of the drug payloads and nanocarriers following intravenous administration of doxorubicin(DOX)-loaded methoxy polyethylene glycol-polycaprolactone(mPEG-PCL) nanoparticles. Comparison of the kinetic profiles of both DOX and nanocarriers verifies the long-circulating effect, though of limited degree, as a result of pegylation. The nanocarrier profiles display fast clearance from the blood despite dense PEG decoration;DOX is cleared faster than the nanocarriers. The nanocarriers circulate longer than DOX in the blood, suggesting possible leakage of DOX from the nanocarriers. Hepatic accumulation is the highest among all organs and tissues investigated, which however is reversely proportionate to blood circulation time. Pegylation and reduction in particle size prove to extend circulation of drug nanocarriers in the blood with simultaneous decrease in uptake by various organs of the mononuclear phagocytic system. It is concluded that the long-circulating effect of mPEG-PCL nanoparticles is reconfirmed by monitoring of either DOX or the nanocarriers, but the faster clearance of DOX suggests possible leakage of a fraction of the payloads. The findings of this study are of potential translational significance in design of nanocarriers towards optimization of both therapeutic and toxic effects.

近红外响应型盐酸青藤碱贮库微针的制备与表征

该文拟设计并制备近红外响应型盐酸青藤碱贮库微针,通过对其机械力学性质及体外释放特征的表征,以评价该类型微针提高载药量和经皮吸收的可行性。选择盐酸青藤碱为模型药物,以单甲氧基聚乙二醇-聚己内酯嵌段共聚物(MPEG-PCL)和吲哚菁绿(ICG)为两亲性嵌段共聚物和光诱导剂,制备近红外响应型纳米粒,并基于气泡微针(bubble microneedle)制备原理,设计并制备近红外响应型盐酸青藤碱贮库微针;通过测定微针形态、长度、力学性能、皮肤刺入特征等表征近红外响应型盐酸青藤碱贮库微针制剂特征,同时,采用体外释放试验评价贮库式微针的释药性能。结果显示,所制备的盐酸青藤碱微针呈圆锥形,暴露针尖高度约650μm,每平方厘米可容纳约0.5 mg药物,且该类型微针机械力学性能和皮肤刺入能力良好,体外释放实验显示,该微针24 h单位面积累积释放量和释放率分别为825.61μg·cm^(-2)和74.3%,其释放动力学符合一级动力学模型。该研究初步证明贮库式微针可有效提高微针的载药量,且机械性能和释放性能良好。

pH敏感电荷反转型姜黄素纳米粒子的制备及体外评价

目的制备pH敏感电荷反转型姜黄素纳米粒子(PCE/Cur NPs),优化制备工艺并考察PCE/Cur NPs的理化性质及其对黑色素瘤(B16)细胞的抑制作用。方法在正电性材料甲氧基聚乙二醇-聚己内酯-聚乙烯亚胺(MPEG-PCL-PEI,PCE)的基础上键合1,2-环己二酸酐使其变成负电性材料,制备带负电的PCE/CurNPs,该纳米粒子具有pH值依赖性,pH值>7时,PCE/Cur NPs不发生化学变化,显示负电性,pH值<6时,PCE/Cur NPs发生化学反应,水解掉1,2-环己二酸,显示正电性。考察了其形态、粒径、载药量、包封率与体外释放等理化特性;通过MTT法、划痕实验进行检测,验证PCE/Cur NPs对B16细胞的抑制作用、抗增殖侵袭能力。结果获得了PCE/Cur NPs,透射电子显微镜下观察所得纳米粒子形态外观圆整,大小均匀,无黏连,平均粒径为(80±5)nm;包封率为(90.0±2.0)%;载药量为(8.0±1.0)%;48 h时,PCE/Cur NPs释放趋于恒速,释放缓慢,累积释放达到(69.2±5.2)%(pH 7.4)与(71.2±4.3)%(pH 5.0);细胞实验显示,PCE/Cur NPs能够显著抑制B16细胞的生存和增殖能力,具有剂量和时间依赖性。结论成功制备了PCE/CurNPs,对抑制B16细胞增殖效果良好,为开发智能型抗肿瘤给药系统提供了理论依据。

不同疏水结构的两亲性聚合物对MDCK-MDR1细胞P-糖蛋白功能的影响

目的研究不同疏水结构的两亲性聚合物单甲醚聚己二醇-聚己内酯聚合物(m PEG-PCL)、单甲醚聚乙二醇-聚D,L-乳酸聚合物(m PEG-PDLLA)、单甲醚聚乙二醇-聚(乳酸-羟基乙酸)聚合物(m PEG-PLGA)对P-糖蛋白(P-glycoprotein,P-gp)外排功能的影响。方法采用薄膜分散法制备聚合物胶束,动态光散射仪测定胶束粒径,芘荧光探针法测定临界胶束浓度(CMC);以P-gp特异性底物罗丹明123(Rhodamine 123,R123)为荧光探针,采用摄取和外排实验评价聚合物及其形成的胶束对MDCK-MDR1细胞P-gp功能的影响。结果m PEG-PCL、m PEG-PDLLA、m PEG-PLGA的粒径分别为(55.9±0.2)、(53.7±1.1)和(61.6±0.6)nm;CMC值分别为2.08、5.42和26.4μg·m L^(-1);摄取实验结果显示,当m PEG-PCL质量浓度在250μg·m L^(-1)、m PEG-PDLLA在1~25μg·m L^(-1)、m PEG-PLGA在1~25μg·m L^(-1)时,可显著增加细胞内R123累积量,表明三者对P-gp外排功能均有抑制作用;外排实验中m PEG-PCL、m PEG-PDLLA、m PEG-PLGA分别在CMC以上、CMC附近及以下、CMC以下时会显著降低R123外排率,与摄取实验结果相对应。结论 m PEG-PCL、m PEG-PDLLA、m PEG-PLGA聚合物对P-gp外排活性均有一定的抑制作用,其作用程度与疏水段结构、聚合物浓度及存在状态有关。