抗VEGF单克隆抗体偶联5-FU纳米微粒的初步研究

目的： 为了提高5-氟尿嘧啶(5-fluorouracil, 5-FU)的抗癌活性，采用抗VEGF单克隆抗体与 5-FU 聚乳酸纳米微粒交联结合制备具有靶向功能的免疫纳米微粒。 方法： 采用抗VEGF单克隆抗体与已制备的 5-FU 聚乳酸纳米微粒(5-FU-NPs)以化学键偶联连接的方法制备具有靶向功能的5-FU免疫纳米微粒(5-FU-Ab-NPs)，考察其形貌、粒径分布、体外释放和免疫活性等性能。结果： 5-FU-Ab-NPs仍呈规则球形，粒径约为（202±23）nm，体外释放实验表明该5-FU-Ab-NPs与5-FU-NPs具有相似缓释特性，免疫学检测和电镜检视显示偶联后的抗VEGF单克隆抗体免疫活性保持原活性的80%以上。结论： 5-FU-Ab-NPs保持原5-FU-NPs缓释药物的特点，具有双重活性功能，即免疫导向和缓释药物,有利于提高肿瘤局部药物浓度。     

聚乳酸载药纳米微粒的表面修饰及体外评价

本研究的目的是用O 羧甲基壳聚糖作乳化剂和表面修饰剂 ,采用超声乳化法制备聚乳酸载药纳米微粒 ,并对聚乳酸载药纳米微粒进行表面修饰 ,然后分别对载药纳米微粒的表面形貌、粒径分布、微粒结构、表面元素、体外释放和肿瘤细胞抑制率等微粒性能进行考察与评价。实验证明 ,O 羧甲基壳聚糖可用于制备纳米药物载体系统 ,对聚乳酸载药纳米微粒的制备起到很好的乳化性能和表面修饰作用。采用复乳法制备包载 5 Fu的PLA/O CMC纳米微粒的平均粒径在 5 0nm ,在PBS缓冲溶液中释放时间可达 12d。在对胃癌、乳腺癌和大肠癌三种肿瘤细胞的抑制率测定实验中 ,PLA/O CMC纳米微粒的肿瘤细胞抑制率分别可以达到 72 .8%、77.3%和 75 .6 % ,接近或等同于游离 5 Fu药物的抑制率。在作用时间上 ,PLA/O CMC载药纳米微粒也显示出良好的缓释效应。     

立体定位注射靶向功能载药纳米粒子治疗恶性脑胶质瘤

以转铁蛋白溶液为外水相，纳米沉淀技术制备了表面含转铁蛋白的包载卡莫司汀的聚乳酸纳米微粒，药物释放时间达一周以上。体外细胞实验验证纳米微粒表面转铁蛋白保持了活性，纳米粒子与胶质瘤细胞具有较强的结合能力。立体定位注射纳米微粒至荷瘤鼠瘤腔，SPECT考察载药纳米微粒的体内分布，表明纳米微粒在颅内滞留。与对照组相比，注射载药纳米微粒的大鼠生存期显著延长，核磁共振图象显示其中2只大鼠颅内肿瘤消退，表明载药纳米粒子对恶性胶质瘤具有体内抑制作用。     

阿霉素及棉酚双药纳米载体对U87胶质瘤细胞的协同抑制作用

目的:建立一种具有协同治疗效果的阿霉素及棉酚双药纳米载体,并检测其协同抗神经胶质瘤的效果。方法:通过MTT法检测阿霉素和棉酚对人脑胶质瘤细胞U87的协同抑制作用,使用透明质酸和阳离子两亲性淀粉为材料构建双药纳米载体,并对其性能进行表征,利用荧光标记的纳米载体观察其在U87细胞和体内模型上的靶向递送水平,最后检测双药纳米载体体内抗肿瘤效果。结果:阿霉素和棉酚针对U87细胞有显著的协同抑制效果,所制备的双药纳米载体粒径为145.7 nm±5.6 nm,棉酚的包裹率为93.8%±2.5%载药量18.2%±2.1%;盐酸阿霉素的包裹率为89.4%±4.7%载药量1.9%±0.6%,72 h阿霉素释放率小于40%,低于40℃环境下稳定时间超过5周。药纳米载体可在1 h内即可在U87细胞中达到较高的积累量,并持续释放携带的药物,细胞抑制效果与游离双药一致,体内实验表明,双药纳米载体可有效靶向肿瘤组织,体内抑瘤效果显著,抑瘤率高于90%,明显好于游离给药组,且毒性降低。结论:阿霉素与棉酚双药纳米载体可将两种药物有效递送至肿瘤组织和细胞内,并发挥出显著的协同抑瘤作用。     

紫杉醇聚合物胶束及其抗肿瘤活性研究

目的 以聚己内酯-聚乙二醇-聚己内酯（PCL-PEG-PCL）为载体材料,制备载紫杉醇聚合物胶束,并评价其对EMT-6乳腺癌的抗肿瘤效果.方法 采用薄膜-超声法制备载紫杉醇聚合物胶束并对其进行表征;采用差示扫描热分析法（DSC）分析紫杉醇在载药聚合物胶束中的分散状态;采用MTT法研究紫杉醇聚合物胶束对EMT-6乳腺癌细胞的细胞毒性;建立荷EMT-6乳腺癌小鼠模型,以市售紫杉醇注射液为对照,研究紫杉醇聚合物胶束的体内抗肿瘤活性.结果 紫杉醇聚合物胶束为表面粗糙的球形,具有明显核壳结构,平均粒径为93nm;DSC研究结果表明,将紫杉醇制成缓释纳米粒后其结晶状态发生了变化,以无定型状态存在于聚合物胶束中;MTT研究表明,在相同紫杉醇含量下,紫杉醇聚合物胶束的细胞毒性低于市售紫杉醇／聚氧乙烯蓖麻油注射剂;体内抗肿瘤活性研究表明,紫杉醇聚合物胶束对小鼠EMT-6乳腺癌具有明显抑制作用,相同给药剂量下其抑瘤效果优于紫杉醇注射剂（肿瘤抑制率：85.79％ vs 63.37％,P＜0.05）.结论 制备的载紫杉醇聚合物胶束高效低毒,是一种有潜力的可用于肿瘤治疗的纳米载药体系.     

胰岛素纳米粒子缓释制剂的实验研究

目的研究胰岛素纳米级粒子缓释制剂的体内生物作用,以期在临床上实现胰岛素注射剂的更长效稳定释放给药治疗糖尿病.方法以聚乳酸-聚乙醇酸共聚物(PLGA)作为基质材料,采用超声乳化/溶剂挥发法制备PLGA包囊胰岛素的纳米级微粒(NP),借助扫描电镜观察微粒形态,通过激光光散射实验测定纳米微粒的粒径分布;利用高效液相色谱(HPLC)测定纳米微粒制剂的载药率;并做纳米胰岛素制剂在糖尿病动物模型体内的药效学研究.结果经电镜观察PLGA-胰岛素NP为表面光滑的球形微粒,粒径分布平均值是112.4nm,呈正态分布;PLGA-胰岛素NP载药率为7.4%;体内研究表明,所制备的纳米制剂生物活性没有改变;皮下注射途径给药纳米胰岛素可以在至少72小时内长效控释,有效降低血糖并保持在正常范围.此外纳米制剂的量-效关系明显,未见任何不良反应.结论PLGA纳米粒子可以作为胰岛素的有效载体,达到更长效稳定控制释放的目的,发挥药物更佳的降糖作用.     

PLGA/O-CMC载药纳米微粒的体外降解及释药行为研究

本研究以聚乳酸-乙醇酸共聚物（PLGA）和自行制备的O-羧甲基壳聚糖（O-CMC）为原料，以5-氟尿嘧啶（5-FU）为抗癌药物模型，采用自身设计的改良复乳法制备了载药纳米微粒。微粒平均粒径为98.5nm，粒径分布指数为0.192，粒子表面∈电位为61．48eV，载药率高达18.9％。然后用SEM动态监测载药纳米粒子降解过程中表面形貌的变化，并连续追踪粒子降解过程中的质量损失和降解介质的pH变化。载药纳米粒子在PBS中的释药行为研究表明，（1）前12h的释药动力学符合Huguchi方程，具有一级释放特性；（2）在20d内的释药动力学符合零级释放特性。细胞凋亡实验结果表明载药纳米粒子对TJ905脑胶质瘤细胞增殖有明显的抑制作用。     

磁性吉西他滨隐形纳米脂质体的制备及其体外抑瘤实验

目的 研究制备磁性吉西他滨隐形纳米脂质体(MGSL)的最佳条件并考察其理化性质以及在体外的抑瘤效应. 方法 通过逆相蒸发法制备MGSL,采用扫描电镜和原子力显微镜对其形态进行观察;利用激光粒度分析仪测定MGSL粒径大小和粒度分布;通过高效液相色谱法(HPLC)检测药物的载药量和包封率;使用专业磁性测试仪进行体外磁响应性测定.观察MGSL诱导的乳腺癌MCF-7细胞凋亡过程中的细胞形态学改变,MTT法获得MGSL作用乳腺癌细胞生长抑制率.流式细胞术分析MGSL引起的细胞凋亡率和细胞周期分布. 结果 MGSL为圆形或椭圆形,大小均匀一致,其平均粒径为206.6纳米,粒度分布窄,大小均匀.MGSL载药量为(10.4±0.7)%,包封率为(81.7±5.1)%.在体外,MTT实验结果与MGSL及游离的吉西他滨相对照,MGSL对人乳腺癌细胞有明显的杀伤作用,而且该作用随浓度升高有上升趋势;作用2h时在相同的浓度下较裸药组的抑瘤作用低(P<0.05),但作用48h后两组的抑制率无差别(P<0.05);另外MGSL比磁性吉西他滨纳米脂质体(MGL)的抑制率略低,但无统计学差异(P>0.05);乳腺癌细胞周期分布结果显示,MGSL是主要作用于S期的细胞周期药物;另外流式细胞术也证实了MGSL还有促乳腺癌细胞凋亡的作用,其诱导凋亡率达到51.62%. 结论 本法制备的MGSL符合作为纳米磁靶向给药系统的条件,其在体外显示了较好的抑瘤效应,可望成为一种有效的抗肿瘤物质.     

5-氟尿嘧啶聚乳酸载药纳米微粒对胃癌细胞株的体外杀伤作用

背景：5-氟尿嘧啶在胃癌治疗中占据重要地位,但是长期服用容易出现骨髓抑制、白细胞减少等不良反应。聚乳酸及共聚物载药微粒材料生物相容性较高,分解物不会在机体内发生聚集。目的：探讨聚乳酸载药纳米微粒对胃癌细胞株的体外杀伤作用机制。方法：选取10只小鼠进行实验,利用超声乳化方法制备5-氟尿嘧啶聚乳酸载药纳米微粒,并采用噻唑蓝比色法配制1×10^-7,1×10^-6,1×10^-5,1×10^-4 mol/L的5-氟尿嘧啶聚乳酸载药纳米微粒,检测其对小鼠胃癌细胞的体外杀伤效应,并且计算出药物的抑制率浓度以及对胃癌细胞的生长抑制能力等以及凋亡的诱导作用。结果与结论：透射电镜下观察5-氟尿嘧啶聚乳酸载药纳米微粒：形态完好,分布相对均匀,不出现粘连等现象,用药24 h药物浓度可达到50%,72 h后能够达到62.9%;不同浓度下单一5-氟尿嘧啶和5-氟尿嘧啶聚乳酸载药纳米微粒和小鼠胃癌细胞联合培养48 h后,细胞的活性随着药物浓度的提高出现下降趋势,并且5-氟尿嘧啶聚乳酸载药纳米微粒细胞抑制能力显著高于5-氟尿嘧啶(P < 0.05);5-氟尿嘧啶聚乳酸载药纳米微粒的IC₅₀显著低于5-氟尿嘧啶(P < 0.05)。结果证实聚乳酸纳米微粒具有优良的药物载体作用,载药量较大,在机体内提高药物浓度,并且不降低5-氟尿嘧啶成分的生物学活性,可为胃癌治疗提供新思路。 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

植入型表阿霉素缓释药膜的制备及体内抑瘤活性

制备用于实体肿瘤局部治疗的植入型表阿霉素缓释药膜.采用复乳.溶剂挥发法制备聚乳酸载表阿霉素缓释微球,用交联复合法制备含载药微球的植入型胶原药膜;用扫描、透射电镜、共聚焦及粒度仪等考察微球和药膜的形貌、结构、粒径及体外释放;用H22肝癌荷瘤动物模型评价其体内抑瘤效果.结果:载药微球粒径分布均匀,外观圆整,平均粒径为5.8μm;微球的载药量4.39%,包裹率为37.2%;10h内载药微球在模拟体液中的累积释放率为35%;腹腔注射载药微球与瘤体局部植入胶原药膜对H22肝癌均有明显的抑瘤效果;微球注射与药膜植入两种不同给药方式对H22肝癌抑瘤效果也存在显著性差异(P<0.05).植入型载表阿霉素缓释胶原膜具有良好的药物局部缓释特性,在肿瘤的术后局部治疗方面具有良好的临床应用前景.     

A novel antimetabolite, TAS-102 retains its effect on FU-related resistant cancer cells

TAS-102 is a new oral anti-tumor drug preparation, composed of a 1:0.5 mixture (on a molar basis) of alpha,alpha,alpha-tri-fluorothymidine (FTD) and thymidine phosphorylase inhibitor (TPI). TAS-102 is currently undergoing clinical trials, and has been demonstrated to have at least 2 mechanisms; inhibition of thymidylate synthase (TS) and incorporation into DNA. 5-FU is widely used in the treatment of solid tumor, but the inherent or acquired resistance of certain tumors to 5-FU therapy is a major clinical problem. In the present study, we investigated FTD in vitro and in vivo comparing with 5-FU and using FU-resistant cells. There was no relationship between FTD and 5-FU growth inhibition effect in vitro. A different sensitivity pattern was observed by the log-mean graph. We next investigated the anti-tumor activity of TAS-102 in a FU-resistant xenograft model. Comparative efficacy was observed between FU-resistant cell and its parent cell. We also studied the influence of TAS-102 on liver metastasis in a mouse model of human colorectal cancer, because liver metastasis of colorectal cancer is associated with patient survival. Human cancer DNA was detected by PCR, and TAS-102 markedly inhibited the number of liver metastasis. A novel angiogenic factor, platelet-derived endothelial cell growth factor (PD-ECGF), was shown to be identical to a previously characterized intracellular enzyme, thymidine phosphorylase, TAS-102 can be expected to have not only anti-tumor cytocidal effects but also antiangiogenesis activity and may inhibit liver metastasis. Our findings suggested that TAS-102 is a promising candidate for clinical use and can be expected to decrease minimal residual disease.     

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,24 h内5-氟尿嘧啶累积释药量达36.2%,10 d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。     

Preparation and characterization of cross-linked microspheres C(Dex-g-PSSS) and their drug-carrying and colon-specific drug delivery properties

The graft polymer Dex-g-PSSS was obtained through poly(sodium 4-styrene sulfonate) (PSSS) grafted on dextran(Dex) by using the cerium salt–hydroxyl group redox initiation system. The cross-linked microspheres C(Dex-g-PSSS) were synthesized by suspension polymerization with epichlorohydrin as the cross-linking agent. The chemical structure and physicochemical characteristics of C(Dex-g-PSSS) microspheres were represented by infrared spectroscopy (FTIR), optical microscope, and zeta potential analysis. The aim of the study is to constitute a colon-specific drug delivery system via molecular design, using C(Dex-g-PSSS) microspheres as the drug-carrying material and taking 5-fluorouracil (5-FU) as the model drug. The drug-carrying ability and mechanism of the cross-linked microspheres C(Dex-g-PSSS) for 5-FU were investigated. Finally, in vitro release tests for the drug-carrying microspheres were conducted. The experimental results show that in the medium with pH 2, the cross-linked microspheres C(Dex-g-PSSS) exhibit a strong adsorption ability for 5-FU because of strong electrostatic interactions and have an adsorption capacity of 154 ± 7.5 mg/g, displaying high drug-carrying efficiency. The in vitro release behavior of the drug-carrying microspheres is highly dependent on pH and dextranase. In the medium with pH 2, the drug-carrying microspheres do not release the drug and in the medium with pH 1, they release a little, whereas in the medium with pH 7.4, a sudden delivery phenomenon of the drug will occur, and in the presence of dextranase, a more sudden delivery phenomenon of the drug will occur, displaying an excellent colon-specific drug delivery behavior.     

静电纺丝制备聚丙交酯超细纤维

对溶液静电纺丝制备直径小于200 nm的超细聚D,L-丙交酯(PLA)纤维进行研究,以期获得与细胞外基质尺度相近的组织修复物。以扫描电镜观察纤维形貌,结果表明溶剂是决定PLA超细纤维形成的关键因素,与丙酮相比,N,N-二甲基甲酰胺是PLA静电纺丝较为理想的溶剂。在PLA溶液中加入有机盐三乙基苯氯化铵,可使溶液的电导率大大提高,从而导致PLA超细纤维直径从500 nm降低至100~200 nm。表面活性剂Span-80的加入并没有使PLA超细纤维变得更细,而是形成了带有珠状缺陷的纤维网。     

5-Fluorouracil–lipid conjugate: Potential candidate for drug delivery through encapsulation in hydrophobic polyester-based nanoparticles

The encapsulation of 5-fluorouracil (5-FU) in hydrophobic polymeric materials is made feasible by a lipid-based prodrug approach. A lipid–5-FU conjugate of 5-FU with palmitic acid was synthesized in two-step process. A synthesized dipalmitoyl derivative (5-FUDIPAL) was characterized using Fourier transform infrared spectroscopy and ¹H-nuclear magnetic resonance. The 5-FUDIPAL was encapsulated in polyester-based polymers by the double emulsion–solvent evaporation method. The nanoparticles were characterized by scanning electron microscopy, transmission electron microscopy and dynamic light scattering. The thermal stability was assessed by differential scanning calorimetry data. In vitro release kinetics measurements of the drug from nanoparticles showed the controlled release pattern over a period of time. Cytotoxicity measurements by MTT assay confirmed that dipalmitoyl derivative in nano formulation successfully inhibited the cell growth. Thus the combined physical and biological evaluation of the different polyester-based nanoparticle containing the modified drug showed a facile approach to delivering 5-FU to the tumour site with enhanced efficacy.     

Preparation of poly(D,L-lactide) nanoparticles assisted by amphiphilic poly(methyl methacrylate-co-methacrylic acid) copolymers.

When co-precipitated with amphiphilic copolymers from DMSO, poly(D,L-lactide) (PLA) can be readily converted into stable sub-200 nm nanoparticles by addition of an aqueous phase, free of any polymeric stabilizers such as poly(vinyl alcohol) or Poloxamer. In this work, the ability of random poly(methyl methacrylate-co-methacrylic acid) copolymers (PMMA-co-MA) to stabilize PLA nanoparticles was demonstrated, and the properties of PLA/PMMA-co-MA nanoparticles were investigated. When co-precipitated with PMMA-co-MA, PLA was totally converted into nanoparticles using a polymer concentration in DMSO (Cp) below 17.6 mg ml(-1), and a PMMA-co-MA proportion above a critical value depending on the content of MA repeating units (X). For instance, the lowest PMMA-co-MA proportion required was 0.9 mg mg(-1) PLA for X = 12%, and 0.5 mg mg(-1) PLA for X = 25% (for C(PLA) = 16 mg ml(-1) DMSO). The nanoparticle diameter was essentially independent of X, the proportion of PMMA-co-MA, and the PLA molecular weight, except for oligomers for which the nanoparticle diameter was smaller. It decreased when the organic phase was diluted (126 +/- 13 nm for Cp = 17.6 mg ml(-1), and 81 +/- 5 nm for C(P) = 5.6 mg ml(-1)). The time-dependence of the stability and the degradation of PLA/PMMA-co-MA nanoparticles was discussed. One of the main advantages of this technique is the ability to control surface properties and to bring functional groups to otherwise non-functionalized PLA nanoparticles. To illustrate this, a conjugate of PMMA-co-MA25 and biotin was synthesized, and used to prepare biotinylated nanoparticles that could be detected by fluorescence and transmission electron microscopy after infiltration into ligatured rat small intestine.     

Self-assembled nanoparticles based on hyaluronic acid-ceramide (HA-CE) and Pluronic® for tumor-targeted delivery of docetaxel

Hyaluronic acid-ceramide (HA-CE)-based self-assembled nanoparticles were developed for intravenous docetaxel (DCT) delivery. In this study, physicochemical properties, cellular uptake efficiency, and in vivo targeting capability of the nanoparticles developed were investigated. DCT-loaded nanoparticles composed of HA-CE and Pluronic 85 (P85) with a mean diameter of 110-140 nm were prepared and their morphological shapes were assessed using transmission electron microscopy (TEM). DCT release from nanoparticle was enhanced with increasing P85 concentrations in our in vitro model. Blank nanoparticles exhibited low cytotoxicity in U87-MG, MCF-7 and MCF-7/ADR cell lines. From cellular uptake studies, the nanoparticles developed enhanced the intracellular DCT uptake in the CD44-overexpressing cell line (MCF-7). The nanoparticles were shown to be taken up by the HA-CD44 interaction according to DCT and coumarin 6 (C6) cellular uptake studies. The multidrug resistance (MDR)-overcoming effects of DCT-loaded HA-CE/P85-based nanoparticles were also observed in cytotoxicity tests in MCF-7/ADR cells. Following the intravenous injection of DCT-loaded cyanine 5.5 (Cy5.5)-conjugated nanoparticles in MCF-7/ADR tumor-bearing mice, its in vivo targeting for CD44-overexpressing tumors was identified by non-invasive near-infrared (NIR) fluorescence imaging. These results indicate that the HA-CE-based nanoparticles prepared may be a promising anti-cancer drug delivery system through passive and active tumor targeting.     

聚乳酸纳米微粒的制备及其在鼠脑组织中的选择性分布研究

制备聚乳酸(polylactic acid, PLA)纳米微粒(以下简称PLA纳粒),研究该载体在小鼠脑组织中的分布特征,探讨其对鼠血脑屏障的透过能力。纳米沉积法制备空白及经聚山梨醇80(T-80)表面修饰的PLA纳粒,透射电镜观测其微观形貌、粒径,zeta电位/粒度分析仪分别测定粒度分布范围和zeta电位值;荧光分光光度计检测PLA纳粒能否进入小鼠脑部;透射电镜观察脑组织中纳粒的分布区域。所制PLA纳粒为规整、均匀的球形颗粒, 其等效粒径为162.1nm, 多分散系数为0.108;T-80修饰的PLA纳粒能特异性地分布于小鼠脑组织,电镜结果显示脑微血管内皮细胞中有纳粒的聚集,神经元间隙也有少量分布。结论:表面修饰的PLA纳粒能较特异性地被鼠脑血管内皮细胞摄取,并能够通过血脑屏障。该载体可望成为选择性作用于脑组织的优良给药载体。     

5-氟尿嘧啶载自组装水凝胶纳米粒的制备及体外释放

本实验以乙酰化普鲁兰(PA)为基质材料,采用透析法制备新型自组装水凝胶纳米粒,用以增强5-氟尿嘧啶的药物靶向性及药物选择活性,从而达到降低其毒副作用的目的。用傅立叶红外光谱仪(FT-IR)、动态光散射仪(DLS)和场发射扫描电镜(FE-SEM)对其进行表征。分别测量不同浓度、温度以及储存时间下,PA纳米粒的粒径的变化情况,以研究环境因素的改变对PA纳米粒的粒径及其粒径分布的稳定性影响。使用透析方将5-氟尿嘧啶(5-FU)物理包封于自组装纳米粒中,并模拟人体环境进行了体外释放研究。结果表明,PA纳米粒在不同环境条件下,粒径基本保持恒定,具有良好的稳定性;PA纳米粒的粒径在100nm左右,具有良好的表面球形度且分布均匀;不同环境条件变化下,粒径基本保持恒定,具有良好的稳定性;在18h内,5-FU释放量达70%左右,具有明显的缓释作用。乙酰化程度越低,5-FU的缓释效果越好,但载药量略有下降。PA纳米粒是非常具有应用前景的新型5-FU药物载体。