Bio-distribution and anti-tumor efficacy of PEG/PLA nano particles loaded doxorubicin

As a more effective in vivo drug delivery system, several methods loading anti-cancer drugs to biodegradable and biocompatible nano-particles have been explored and developed. Supposedly due to the enhanced permeability and retention (EPR) effect, systemic administration of these nano-particles have been found to result in accumulation of nano-particles into solid tumors. In this study, we prepared nano-particles using polyethylene glycol (PEG)/poly-L-lactide (PLLA) diblock copolymer and loaded doxorubicin into these nano-particles (Nano-dox). The fabricated nano-particles exhibited sustained release kinetics of the drug in vitro. To follow the in vivo biodistribution of 200-350 nm sized nano-dox particles in tumor (syngenic renal cell adenocarcinoma: RENCA) bearing mouse, the carboxylfluorescenin diacetate succinimidyl ester (CFSE) was loaded into the nano-particles. Nano-dox accumulated preferentially in tumors; however, in terms of its anti-tumor efficacy, it did not show any marked benefits, compared to freely-administered doxorubicin. This result suggests the need to re-consider and evaluate what type of anti-cancer reagents we to be used in the ongoing efforts of coupling drug delivery system with tumor EPR effects.     

负载阿霉素的黄芩苷纳米粒的制备及其体外性能评价

目的 制备负载阿霉素的黄芩苷纳米粒（DOX/SA-SS-BAI NPs）,并评价其体外性能。方法 构建以胱胺为连接臂的海藻酸钠–黄芩苷聚合物,并负载阿霉素,得到DOX/SA-SS-BAI NPs。对DOX/SA-SS-BAI NPs的理化性质进行表征;采用HepG2细胞进行MTT实验验证其细胞毒性。结果 DOX/SA-SS-BAI NPs粒径为（158.2±2.8）nm,PDI为（0.241±0.008）,Zeta电位为（-24.1±0.3）m V,包封率为（64.34±0.25）%,载药量为（16.22±0.06）%。体外释放显示载药纳米粒具有良好的还原响应性;MTT实验证明DOX/SA-SS-BAINPs对HepG2细胞具有良好的抑制作用;细胞摄取实验表明DOX/SA-SS-BAI NPs在HepG2细胞内较快地释放阿霉素。结论 制备的DOX/SA-SS-BAI NPs具有较好的理化性质和体外抗癌作用。     

Solubilization of flurbiprofen into aptamer-modified PEG–PLA micelles for targeted delivery to brain-derived endothelial cells in vitro

Abstract

Novel aptamer-functionalized polyethylene glycol–polylactic acid (PEG–PLA) (APP) micelles were developed with the objective to target the transferrin receptor on brain endothelial cells. Flurbiprofen, a potential drug for therapeutic management of Alzheimer’s disease (AD), was loaded into the APP micelles using the co-solvent evaporation method. Results indicated that 9.03% (w/w) of flurbiprofen was entrapped in APP with good retention capacity in vitro. Targeting potential of APPs was investigated using the transferring receptor-expressing murine brain endothelial bEND5 cell line. APPs significantly enhanced surface association of micelles to bEND5 cells as quantified by fluorescence spectroscopy. Most importantly, APPs significantly enhanced intracellular flurbiprofen delivery when compared to unmodified micelles. These results suggest that APP micelles may offer an effective strategy to deliver therapeutically effective flurbiprofen concentrations into the brain for AD patients.     

载阿霉素透明质酸聚合物纳米粒的构建及其体外性质研究

目的 合成透明质酸（HA）接枝单油酸甘油酯（GMO）两亲性聚合物HGO,并研究其所制备载阿霉素（DOX）纳米粒的理化性质及体外抗肿瘤效果。方法 HA与GMO通过酯化反应制得载体聚合物HGO,通过核磁共振波谱法及红外光谱法对其进行结构表征;采用芘荧光探针法测定聚合物临界聚集浓度（CAC）。采用透析法制备聚合物HGO载阿霉素（DOX@HGO）纳米粒,并对其进行粒径分布、Zeta电位及微观形态的表征;通过检测其在不同离子强度、不同pH条件下的粒径变化考察纳米粒的体外稳定性;考察DOX@HGO纳米粒在不同pH条件下的体外释放行为;CCK-8法考察DOX@HGO纳米粒对MDA-MB-231细胞的体外抑瘤效果;并通过荧光显微镜研究MDA-MB-231细胞对DOX溶液、DOX@HGO纳米粒的摄取能力,以及HA预处理对DOX@HGO纳米粒摄取的影响。结果 成功制得两亲性聚合物HGO,聚合物HGO中GMO的取代度为15.8%,CAC为0.023 mg·mL^-1。DOX@HGO纳米粒呈规则的球形,平均粒径为（130.800±1.709）nm,平均电位为（-32.600±0.153）mV,包封率和载药量分别为（98.65±0.74）%和（33.03±0.17）%,在不同离子强度下、模拟胃肠液中表现出良好的稳定性;DOX@HGO纳米粒的体外释放表现出pH依赖性。体外抗肿瘤活性实验表明,DOX@HGO纳米粒对MDA-MB-231细胞的生长具有较好的抑制作用;与DOX溶液比较,DOX@HGO纳米粒显著增加肿瘤细胞对于DOX的摄取（P＜0.05） ,HA预处理显著减少肿瘤细胞对DOX@HGO的摄取（P＜0.05）。结论 所构建的DOX@HGO纳米粒具有良好的理化性质,并且具有一定的pH敏感性及靶向抗肿瘤细胞的能力,是具有应用潜力的药物载体。     

载巯基化阿霉素的中空金纳米粒的制备与光热性能研究

目的 制备一种载阿霉素（DOX）的中空金纳米粒（HGNPs）载体。方法 合成巯基化阿霉素（DOX-SH）,通过质谱（MS ESI）和核磁共振氢谱（1H-NMR）对其结构进行表征,再将其以金硫键共价结合方式负载到中空金纳米粒表面。通过粒径、等离子共振吸收（SPR）、透射电子显微镜（TEM）、近红外（NIR）激发的光热转化实验和细胞毒性实验对制备的中空金纳米粒载药体系进行评价。结果 质谱显示,合成的巯基化阿霉素的分子量为616,核磁共振氢谱所示的结构也与目标产物相符。阿霉素-中空金纳米粒复合载药体系(HGNPs-DOX)的粒径为70 nm左右;等离子共振吸收最大吸收波长为800 nm左右,具有良好的光热转化能力;透射电子显微镜显示,其为中空圆球形结构,壳厚4~6 nm;细胞毒性显示,在高浓度时,阿霉素-中空金纳米粒复合载药体系能显著减小阿霉素的毒性。结论 成功合成了阿霉素-中空金纳米粒复合载体,其具有良好的结构,良好的光热转化能力,较小的细胞毒性,未来可成为有研究前景的新一代化疗联合光热治疗的递送载体。     

阿霉素修饰纳米银的制备及其体外抗肿瘤活性研究

摘要： 目的 设计合成一类新型的具有pH响应性的阿霉素-纳米银 （DOX-Ag NPs） 联合抗肿瘤药物, 对其理化性质进行表征, 并研究其体外响应性释药行为和抗肿瘤活性。方法 通过硫辛酰肼 （LA-NHNH2 ） 连接纳米银 （Ag NPs） 和阿霉素 （DOX）, 得到DOX-Ag NPs。利用核磁氢谱 （1 H NMR） 和高分辨质谱 （HRMS） 对硫辛酰肼-阿霉素 （LA- NHN=DOX） 进行结构确证; 通过动态光散射 （DLS） 和透射电镜 （TEM） 分析纳米粒的粒径和形貌; 通过紫外-可见吸收光谱和荧光光谱表征纳米粒的光学性质; 通过透析法结合荧光光谱检测DOX-Ag NPs在不同pH下的DOX释放行为; 采用噻唑蓝比色法研究DOX-Ag NPs对HepG2肿瘤细胞的增殖抑制效果。结果 LA-NHN=DOX的1 H NMR数据及HRMS检测到746.275 6处的分子离子峰均证明LA-NHN=DOX成功合成。DOX-Ag NPs为粒径 （40.4±3.8） nm的球形纳米粒; 在弱酸性条件下DOX-Ag NPs能够快速响应性释放DOX; DOX-Ag NPs对HepG2肿瘤细胞增殖抑制呈现浓度依赖性, 当DOX浓度为0.5~20 mg/L （Ag浓度为0.45~18 mg/L） 时, DOX-Ag NPs组细胞生存率均明显低于DOX 组和Ag NPs组 （均P＜0.05）。结论 DOX-Ag NPs是一种具有pH响应性的联合抗肿瘤纳米制剂, 能在肿瘤组织快速释放DOX, 并通过与Ag NPs的协同治疗, 发挥良好的体外抗肿瘤作用。     

HPLC-MS/MS determination of a peptide conjugate prodrug of doxorubicin, and its active metabolites, leucine-doxorubicin and doxorubicin, in dog and rat plasma

A HPLC-MS/MS Electrospray (ESI) method was developed and validated to quantify a peptide conjugate prodrug of doxorubicin (Dox-Con) and its active metabolites leucine-doxorubicin (Leu-Dox) and doxorubicin (Dox) in dog and rat plasma. The analytes were extracted from plasma by solid-phase extraction on a Bond Elut® C8 cartridge and eluted with chloroform–methanol (2:1). Eluates were evaporated and reconstituted in acetonitrile–5 μM sodium trifluoroacetate in 0.1% aqueous formic acid (20:80) and injected onto a Waters Oasis® HLB column. Analytes were eluted from the column with a solvent gradient into the mass analyzer. The ions were quantified in the selected reaction-monitoring mode (SRM), using positive ions, on a triple quadrupole mass spectrometer. The lower limits of quantification for Dox-Con, Leu-Dox, and Dox in plasma, were approximately 5, 1 (dog)/6 (rat), and 0.5 ng/ml, respectively. Intra- and inter-assay accuracy (% of nominal concentration) and precision (%CV) for all analytes were within 15 and 16%, respectively.     

脂质体多柔比星治疗恶性肿瘤临床疗效及安全性的系统评价

目的 评价脂质体多柔比星（脂质体阿霉素）治疗恶性肿瘤的临床疗效及安全性。方法 计算机检索中国学术文献总库（CNKI）、万方数字化期刊库、中国生物医学文献数据库（CBM）、维普中文科技期刊数据库（VIP）,PubMed数据库、Embase数据库和Cochrane Library数据库,脂质体多柔比星治疗恶性肿瘤的中英文随机对照试验,检索年限从建库至2017年1月。采用RevMan 5.3软件对各效应指标进行Meta分析。结果 纳入23篇RCT文献,计5 546名恶性肿瘤患者。Meta分析结果显示：治疗前后临床疗效I²=63%、OR=1.14[1.02,1.27],P=0.002;两组化疗后心脏毒性不良事件I²=0%,OR=0.18[0.10,0.33],P<0.000 01;脱发不良事件I²=77%,OR=0.24[0.17,0.35],P<0.000 01;神经毒性不良事件I²=46%,OR=0.65[0.42,0.99],P=0.05。结论 脂质体多柔比星治疗恶性肿瘤的临床疗效优于其他化疗方案,且毒副作用低,尤其在改善心脏毒性、脱发等不良事件方面明显优于其他化疗方案。     

盐酸阿霉素聚乳酸纳米粒的制备及大鼠体内药动学研究

目的 优化盐酸阿霉素聚乳酸纳米粒（DOX-PLA-NPs）的制备工艺,并对其理化性质、体外释放及大鼠体内药动学进行研究。方法 采用改良的复乳-溶剂挥发法制备DOX-PLA-NPs,正交设计优化其处方工艺,对其纳米粒形态、粒径、Zeta电位、包封率与载药量进行测定。以DOX原药为对照组,考察DOX-PLA-NPs的体外释药特性及大鼠尾静脉给药后的体内药动学参数。结果 DOX-PLA-NPs外观圆整,平均粒径为（125.67±3.80） nm、Zeta电位为（-35.97±1.58） mV、包封率和载药量分别为（81.23±1.46）%,（10.29±0.63）%。体外释放结果显示,DOX经纳米粒包裹后,具明显的缓释作用。DOX原药和纳米粒的体内药动学过程均符合开放式二室模型,t_1/2β分别为（1.15±0.175） h、（6.43±2.12） h,CL分别为（174.76±47.22） h·L^-1、（30.68±11.86） h·L^-1,AUC_0→t分别为（6.01±1.61）μg·h·L^-1、（36.04±13.72）μg·h·L^-1。结论 制备的盐酸阿霉素聚乳酸纳米粒粒径较小、包封率较高,具明显的缓释作用,并能提高药物的生物利用度。     

外泌体携载阿霉素递送体系构建及体外抗肿瘤活性评价

目的 制备肝癌细胞Hep1-6外泌体并对化疗药物阿霉素（DOX）进行包载,以期实现对肿瘤细胞更高的靶向活性与杀伤作用。方法 采用梯度离心法对肿瘤细胞Hep1-6来源的外泌体进行制备分离;采用透射电镜技术、表面标记蛋白表征以及纳米颗粒追踪分析技术对外泌体的形态、特征蛋白、粒径分布和浓度进行表征;采用电穿孔方法实现外泌体对DOX的有效包载,制备包载阿霉素外泌体（EXO_DOX）。采用CCK-8法检测EXO_DOX与DOX（0.5、1、2、3、5、10 μg·mL^-1）体外对 Hep1-6细胞增殖的影响,采用激光共聚焦显微镜观察体外 Hep1-6细胞对 EXO_DOX与 DOX（1 μg·mL^-1）的靶向摄取作用。结果 所制备的外泌体具有形态良好 、 粒度均一的特性且具备外泌体特征膜蛋白 CD63、 CD81、 肿瘤易感基因101（TSG101）的表达;在电穿孔条件为150 V和75 μF下外泌体对DOX具备良好的包载特性;相比于单独给药DOX,在同等质量浓度下 EXO_DOX对 Hep1-6细胞增殖抑制作用显著增强（P＜0.05、0.01）,同时肿瘤细胞对 EXO_DOX的摄取更具靶向性。结论 制备的EXO_DOX较DOX具有更强的体外细胞毒活性,EXO_DOX表现出对肿瘤细胞更高的靶向特性。     

UPLC-MS/MS测定大鼠血浆多柔比星浓度方法的建立及毒代动力学应用

目的 建立一种简便、快速、灵敏的测定大鼠多柔比星血药浓度的超高效液相-质谱联用（UPLC-MS/MS）法,并将其应用于注射用盐酸多柔比星大鼠体内毒代动力学实验。方法 采用ACQUITY UPLC^® BEH C₁₈（50 mm×2.1 mm,1.7 μm）色谱柱,流动相为0.1%甲酸（含2 mmol/L甲酸铵）水溶液-乙腈,梯度洗脱。体积流量为0.4 mL/min,进样量为10 μL。采用电喷雾离子源（ESI）,多反应监测（MRM）方式扫描,以正离子方式进行检测,蛋白沉淀法提取样品。用于定量分析的离子对分别为多柔比星m/z 544.43→m/z 397.08,内标地西泮m/z 285.02→154.40。SD大鼠30只,按体质量随机分为3组,分别单次iv 52.2、61.4、72.3 mg/m²盐酸多柔比星后测定血药浓度,并用DAS 3.1.4软件计算毒代参数。结果 血浆中内源性物质不干扰待测物和内标的测定,多柔比星在0.5～100 ng/mL范围内线性关系良好,定量下限为0.5 ng/mL。多柔比星在0.5、1、20、80 ng/mL 4个浓度的批内批间精密度RSD值为3.21%～12.79%。多柔比星在1、80 ng/mL的提取回收率和基质效应分别为102.00%～103.75%和79.27%～89.34%。SD大鼠分别单次iv给予注射用盐酸多柔比星52.2、61.4、72.3 mg/m²后,多柔比星在大鼠体内的AUC_0-t分别为（2 318.78±282.65）、（3 203.11±829.41）和（3 326.96±546.04） ng·h/mL,C_0.083h分别为（1 720.50±851.19）、（3 363.00±1 458.84）和（2 156.50±919.90）ng/mL。结论 建立的UPLC-MS/MS分析方法灵敏度高、样品处理方法简单、样品分析时间短,可以应用于大鼠多柔比星毒代动力学试验中。     

Amplification of anticancer efficacy by co-delivery of doxorubicin and lonidamine with extracellular vesicles

Chemotherapy is commonly used for the treatment of lung cancer, but strong side effects and low treatment efficacy limit its clinical application. Here, extracellular vesicles (EVs) as natural drug delivery carriers were used to load conventional anticancer drug doxorubicin (DOX) and a chemosensitizer lonidamine (LND). Two types of EVs with different sizes (16k EVs and 120k EVs) were prepared using different centrifugation forces. We found that co-delivery of DOX and LND with both EVs enhanced the cytotoxicity and reduced the dose of the anticancer drug significantly in vitro. Effective delivery of anti-cancer drugs to cancer cells was achieved by direct fusion of EVs with the plasma membrane of cancer cells. On the other hand, DOX and LND inhibited cancer cell proliferation by increasing DNA damage, suppressing ATP production, and accelerating ROS generation synergistically. DOX and LND loaded EVs were also applied to the mouse lung cancer model and exhibited significant anticancer activity. In vivo study showed that smaller EVs exhibited higher anticancer efficiency. In conclusion, the co-delivery of the anticancer drug and the chemosensitizer with EVs may have potential clinical applications for cancer therapy.     

基于藻酸双酯钠的阿霉素/塞来昔布纳米药物晶体的制备及其抗肿瘤作用研究

目的 制备基于藻酸双酯钠的阿霉素/塞来昔布纳米药物晶体（PPDC）,并考察其体外抗肿瘤作用。方法 采用纳米沉淀法制得PPDC混悬液,分别表征PPDC的形态、粒径、电位、药物晶型、药物包载情况、释药性能,通过细胞摄取、细胞毒性、细胞侵袭、细胞黏附评价PPDC对4T1细胞的抑制作用。结果 PPDC混悬液呈规则球形,分散性良好,分布较窄,载药量高。塞来昔布、阿霉素以无定型稳定状态存在于PPDC中。PPDC在体外释放72 h时携载的药物能够有效释放。体外细胞实验表明,PPDC能被4T1细胞摄取,细胞毒作用具有浓度相关性,并显著抑制细胞侵袭和细胞黏附。结论 PPDC有效解决塞来昔布的难溶性、稳定剂毒性大等问题,与阿霉素共载实现两药协同抑制肿瘤细胞生长和转移的作用。     

A novel micelle of coumarin derivative monoend-functionalized PEG for anti-tumor drug delivery: in vitro and in vivo study

In this paper, a novel micelle for anti-tumor drug delivery was reported. Two 7-carboxymethoxy coumarin molecules were immobilized on the terminal group of a methoxy poly(ethylene glycol) chain via l-lysine as linker. The amphiphilic 7-carboxymethoxy coumarin monoend-functionalized methoxy poly(ethylene glycol) (mPEG-Lys-DCOU) chains were self-assembled micelles. Anti-tumor drug doxorubicin was loaded in the mPEG-Lys-DCOU micelles and the release profile was studied. The cytotoxicity of mPEG-Lys-DCOU was evaluated by NIH 3T3 fibroblasts. The drug-loaded micelles were incubated with HepG2 tumor cells to investigate the in vitro anti-tumor effect. The in vivo inhibition efficacy of drug-loaded micelles was carried out on 4T1 breast cancer animal model. The results showed that both hydrophobic and π-π stacking interactions within mPEG-Lys-DCOU amphiphiles were contributed to the self-assembly. Both blank and drug loaded micelles were monodisperse nanoparticles with the average diameters around 300?nm. The release profile exhibited certain pH dependence. The drug release rate at pH?=?5.5 was much faster than that at pH?=?7.4. mPEG-Lys-DCOU amphiphiles were non-toxic to NIH 3T3 fibroblasts. Both in vitro and in vivo studies demonstrated that the inhibition efficacy of drug-loaded micelles were comparable to that of doxorubicin hydrochloride. mPEG-Lys-DCOU micelles are promising carriers for anti-tumor drug delivery.     

Amphiphilic dendritic nanomicelle-mediated co-delivery of 5-fluorouracil and doxorubicin for enhanced therapeutic efficacy

Combination cancer therapy has attracted considerable attention due to its enhanced antitumor efficacy and reduced toxicity granted by synergistic effects over monotherapy. The application of nanotechnology is expected to achieve coencapsulation of multiple anticancer agents with enhanced therapeutic efficacy. Herein, a unique nanomicelle based on amphiphilic dendrimer (AmD) consisting of a hydrophilic polyamidoamine dendritic shell and a hydrophobic polylactide core is developed for effectively loading and shuttling 5-fluorouracil (5-Fu) and doxorubicin (Dox). The yielded drug-encapsulated dendritic nanomicelle (5-Fu/Dox-DNM) has a modest average size of 68.6?±?3.3?nm and shows pH-sensitive drug release manner. The parallel activity of 5-Fu and Dox show synergistic anticancer efficacy. The IC₅₀ value of 5-Fu/Dox-DNM toward human breast cancer (MDA-MB-231) cells was 0.25?μg/mL, presenting an 11.2-fold and 6.1-fold increase in cytotoxicity compared to Dox-DNM and 5-Fu-DNM, respectively. Furthermore, 5-Fu/Dox-DNM significantly inhibits the progression of tumor growth in the MDA-MB-231 xenograft tumor mice model. In conclusion, we have demonstrated that our AmD-based combination therapeutic system has promising potential to open an avenue for coencapsulation of multiple chemotherapeutic agents to promote superior anticancer effect.     

In vivo effect of oracin on doxorubicin reduction,biodistribution and efficacy in Ehrlich tumor bearing mice

BackgroundThe limitation of carbonyl reduction represents one possible way to increase the effectiveness of anthracycline doxorubicin (DOX) in cancer cells and decrease its toxicity in normal cells. In vitro, isoquinoline derivative oracin (ORC) inhibited DOX reduction and increased the antiproliferative effect of DOX in MCF-7 breast cancer cells. Moreover, ORC significantly decreases DOX toxicity in non-cancerous MCF-10A breast cells and in hepatocytes. The present study was designed to test in mice the in vivo effect of ORC on plasma and tissue concentrations of DOX and its main metabolite DOXOL. The effect of ORC on DOX efficacy in mice bearing solid Ehrlich tumors (EST) was also studied.MethodsDOX and DOX + ORC combinations were iv administered to healthy mice. Blood samples, livers and hearts were collected during the following 48 h. DOX and DOXOL concentrations were assayed using HPLC. The mice with inoculated EST cells were treated repeatedly iv with DOX and DOX + ORC combinations, and the growth of tumors was monitored.ResultsORC in combination with DOX significantly decreased DOXOLplasma concentrations during four hours after administration, but this significantly affected neither DOX plasma concentrations nor DOX or DOXOLconcentrations in the liver and heart at any of intervals tested. In EST bearing mice, ORC did not significantly affect DOX efficacy on tumor growth. However, EST was shown to be an improper model for the testing of ORC efficacy in vivo, as ORC did not inhibit DOXOL formation in EST.ConclusionsIn vivo, ORC was able to retard DOXOLformation but was not able to improveDOXefficacy in EST-bearing mice.     

Enhanced antitumour activity of doxorubicin and simvastatin combination loaded nanoemulsion treatment against a Swiss albino mouse model of Ehrlich ascites carcinoma

Doxorubicin (DOX) is the most commonly used anticancer drug; however, it has limited use because prolonged administration may result in severe cardiotoxicity. Simvastatin (SIM), generally prescribed for hypercholesterolaemia, has also shown salubrious results in the monotherapy or combinational drug therapy of different cancers in various models. Nanoparticle drug delivery systems are a novel way of improving therapeutics and also improving the absorption and specificity of drugs towards tumour cells. In this study, we exploited this technology to increase drug specificity and minimize imminent adverse effects. In this study, the antitumour activity of the combination formulas of DOX and SIM, either loaded in water (DOX‐SIM‐Solution) or nanoemulsions (NEs) (DOX‐SIM‐NE), was evaluated in a Swiss albino mouse model of Ehrlich ascites carcinoma. The anticancer effect was assessed by quantifying the change in body weight, mean survival time, and percent increase in lifespan (%ILS), determining haematological and serum biochemical parameters (liver function test, kidney function test and lipid profile parameters) as well as studying the histopathological alterations in liver tissues. We observed a clear increase in %ILS of the DOX‐SIM‐Solution group (265.30) that was double the %ILS of the DOX‐SIM‐NE group (134.70). However, DOX‐SIM‐NE had a non‐toxic effect on the haematological parameters, whereas DOX‐SIM‐Solution increased the levels of haemoglobin and lymphocytes. Furthermore, the encapsulation of SIM and DOX into NEs improved the levels of all serum biochemical parameters compared to the DOX‐SIM‐Solution. A reduction in the side effects of DOX‐SIM‐NE on the liver was also established using light microscopy, which revealed that the morphologies of the hepatocytes of the mice were less affected by administration of the DOX‐SIM‐NE treatment than with the DOX‐SIM‐Solution treatment. The study showed that incorporating SIM into the DOX‐loaded‐NE formulation remarkably improved its efficiency and simultaneously reduced its adverse effects.     

Surface-coated PLA nanoparticles loaded with temozolomide for improved brain deposition and potential treatment of gliomas: development,characterization and in vivo studies

Hydrophobicity of PLA nanoparticles makes them a good substrate for macrophageal and reticulo-endothelial system uptake. Long-circulating properties can be imparted to these particles by coating them with hydrophilic stabilizers. Surface-modified PLA nanoparticles loaded with anti-cancer agent temozolomide were fabricated by solvent evaporation method and coated with surface modifiers. Selection of the surface modifier was based upon uptake of nanoparticles by K9 cells (liver cells). The particles were prepared and characterized for various physicochemical properties using transmission electron microscopy, differential scanning calorimetry, powder X-ray diffraction and in vitro dissolution studies. In vitro BBB permeation studies were performed using the co-culture model developed by using Madin–Darby canine kidney and C6 glioma cells as endothelial and glial cells, respectively. In vitro C6 glioma cell cytotoxicity, cellular proliferation, cellular migration and cellular uptake studies due to developed nanoparticles was assessed. In vivo studies such as pharmacokinetics, qualitative and quantitative biodistribution studies were performed for the developed nanoparticles. Drug-loaded nanoparticles with entrapment efficiency of 50% were developed. PEG-1000 and polysorbate-80 coated nanoparticles were least taken up by the liver cells. Characterization of the nanoparticles revealed formation of spherical shape nanoparticles, with no drug and excipient interaction. In vivo pharmacokinetics of developed nanoparticles depicted enhancement of half-life, area under the curve and mean residence time of the drug. Qualitative and quantitative biodistribution studies confirmed enhanced permeation of the drug into the brain upon loading into nanoparticles with less deposition in the highly perfused organs like lung, liver, spleen, heart and kidney.     

壳聚糖微/纳米粒在定向给药系统中的应用研究

目的：介绍壳聚糖微/纳米粒在新型定向给药系统中的应用,为发展安全高效的壳聚糖微/纳米粒定向给药系统提供参考。方法：综合近年来出版的有关文献,对壳聚糖基本性质,定位给药于各组织部位进行了探讨。结果：壳聚糖微/纳米粒可应用于脑、眼、鼻、口、肺、胃、小肠、结肠等器官靶向给药。结论：壳聚糖微/纳米粒作为一种新型药用辅料,在定位给药系统中已经得到了开发和应用。     

羧基化PEG修饰的磁流体的制备和表征(英文)

制备和表征肿瘤热疗用羧基化PEG修饰的Fe₃O₄磁流体。化学共沉淀方法制备四氧化三铁磁性纳米颗粒,然后用羧基化PEG修饰;用邻二氮菲显色法测定磁流体中铁的含量;沉降方法考察了制备的磁流体的稳定性;通过X射线衍射、透射电子显微镜、红外和振动样品磁强计对制备的磁流体进行表征;测定了磁流体在交变磁场作用下的热效应。羧基化PEG修饰的磁流体稳定性明显优于未修饰的;红外图谱和X衍射图谱证明所制备的磁流体样品由Fe₃O₄组成;透射电镜照片显示磁性粒子分散良好;经X衍射数据计算得磁性粒子的粒径约为5 nm;羧基化PEG修饰磁流体的饱和磁化强度和剩余磁化强度分别为47.01和3.41 emu/g。矫顽力为6.7 Oe;磁流体的特征吸收率为63.0 W/g[Fe]。羧基化PEG修饰的Fe₃O₄磁流体有望用于肿瘤热疗。