壳聚糖包覆二氧化硅纳米粒及其作为蛋白载体的研究

通过壳聚糖在二氧化硅纳米粒表面的沉积制备了壳聚糖包覆的二氧硅（CS@SiO2）。采用BSA作为模型蛋白,研究了CS@SiO2作为蛋白载体的可能性。结果表明,CS@SiO2可有效吸附BSA且可控释放被吸附的BSA。     

甘草酸羧甲基壳聚糖纳米粒的制备及其性能研究

通过正交试验设计优化钙离子交联法制备羧甲基壳聚糖纳米粒工艺条件,以透射电镜观察,纳米粒外观形态圆整;以激光粒度分析仪测定,纳米粒平均粒径为(131.2±5.27)nm;以高效液相色谱法测定,纳米粒包封率为(51.2±0.41)%,载药量为(16.7±0.29)%。对模型药物甘草酸的体外释放性能考察结果表明,所制备的纳米粒具有较好的控制药物释放的作用。     

羟基喜树碱叶酸-壳聚糖纳米粒的制备及其性能研究

为了提高羟基喜树碱对肿瘤组织的靶向性,增强其抗肿瘤活性,延长其在体内的作用时间,以壳聚糖为药物载体,叶酸为肿瘤靶向配体,三聚磷酸钠为聚阴离子,利用静电相互作用的原理,通过离子交联法合成载羟基喜树碱的叶酸-壳聚糖(FA-CTS/HCPT)纳米粒。利用动态光散射、透射电镜以及红外等技术对纳米粒的结构、平均粒径及粒径分布、形态特征、表面电位、稳定性、对药物的包封率及载药量、体外释放等特点进行了初步研究。结果表明,所制得的纳米粒平均粒径为150nm;粒子形态圆整,大小均匀;表面电位+50.1mV;放置数十天纳米粒粒径几乎无变化,纳米粒具有很好的粒度稳定性;对羟基喜树碱包封率最高为89.9%,载药量最高为19.8%;在人工体液pH值为7.4条件下具有很好的缓释作用,用Higuchi方程拟合其体外释放曲线,得Higuchi方程:Q=14.529t1/2+8.3589(R2=0.9247),说明HCPT在人工体液的释放量与时间的平方根成直线关系,符合水不溶性骨架的释药性能。     

自组装海藻酸钠纳米粒的制备及作为鱼藤酮载体的研究

以1-乙基-3-(3-二甲基氨丙基)碳二亚胺(EDC)为偶联剂,将由N’N-二甲基甲酰胺(DMF)活化的脱氧胆酸接枝到海藻酸钠主链的羧基上,得到疏水改性的双亲性海藻酸钠(DSA),DSA在水相自组装形成纳米颗粒,利用紫外荧光分光光度计、动态激光光散射仪和原子力显微镜对其结构性质进行表征,平均粒径为208.7nm,粒径尺寸比较均一且分布较窄,具有较低的临界聚集浓度(criticalaggregation concentration,CAC),而且随着取代度的不断提高,临界聚集浓度不断降低,并将其作为鱼藤酮载体实验发现载药效果良好。     

Survivin siRNA/叶酸偶联O-羧甲基壳聚糖纳米粒的制备

利用叶酸(FA)活性酯与O-羧甲基壳聚糖(O-CMC)合成了具有一定肿瘤靶向性的FA偶联O-CMC(FA-O-CMC),用核磁共振(1H-NMR)对其结构进行了表征。采用离子交联法,以CaCl2为交联剂,制得了Survivin siRNA/FA-O-CMC纳米粒。扫描电镜(SEM)、激光粒度仪和紫外-可见光谱等分析结果表明,纳米粒分散均匀,当CaCl2∶FA-O-CMC和siR-NA∶FA-O-CMC质量比分别为1∶5和1∶400时,纳米粒粒径为(199.5±23.5)nm,Zeta电位为(-17.39±2.16)mV,包封率和载药量分别为(88.96±1.53)%和(38.25±1.33)%,体外释放实验中,72 h基因释放75%,具有良好缓释性能。     

磁性壳聚糖-5-氟尿嘧啶纳米粒的制备及体外释药性能

采用交联-聚合法在超声波的作用下,制备了磁性壳聚糖-5-氟尿嘧啶纳米粒(M CN-Fu)。透射电子显微镜(TEM)和红外光谱(IR)等分析结果表明,M CN-Fu粒子外形规整,分散性好,粒径主要在50 nm~60 nm之间。紫外-可见光谱分析结果表明,M CN-Fu的载药量为21.3%,在磷酸盐缓冲溶液(pH=7.2)中,30 h的累积释药率为67.6%,具有良好缓释性能,并具有良好磁响应性能。     

PLGA／TPGS-姜黄素纳米粒的制备及体外评价

以维生素E1000聚乙二醇琥珀酸酯（TPGS）为乳化剂,姜黄素为模型药物,聚乳酸-羟基乙酸为载体材料,采用O／W型乳化-溶剂挥发法制备聚乳酸-羟基乙酸-姜黄素纳米粒,以包封率和载药量为主要指标,单因素实验探索影响两指标的主要因素,正交试验设计优化制备工艺,结果表明,制备聚乳酸-羟基乙酸-姜黄素纳米粒的最佳工艺为：聚合物浓度4％,乳化剂TPGS浓度0．03％,超声时间8min,搅拌时间6h。以此工艺制备的载药纳米粒外形圆整光滑,粒度分布较为均匀,平均粒径为189．7nm,包封率为86．2％,载药量为7．45％。     

β-环糊精/O-羧甲基壳聚糖纳米粒对光敏性药物的联合保护

为提高疏水性光敏药物硝苯地平(NF)的光稳定性,用共沉法制得了NF/β-环糊精(NF/β-CD)包合物,再通过离子交联法制得了NF/β-环糊精/O-羧甲基壳聚糖(NF/β-CD/O-CMC)纳米粒。用差示扫描量热仪和X射线衍射仪对NF/β-CD包合物进行了表征;用紫外-可见分光光度计、X射线衍射仪、激光粒度仪和扫描电子显微镜对NF/β-CD/O-CMC纳米粒进行了分析。结果表明,纳米粒包封率和载药量分别为82.38%和18.41%,纳米粒呈多面体形,分散均匀,平均粒径273.80 nm,Zeta电位-37.6 m V,多分散指数(PDI)0.086。紫外光降解实验显示,β-CD包合物对NF有一定的光降解保护作用,β-CD/O-CMC纳米粒中的NF初始1 h降解较快,随后较慢,4 h降解率达到42.43%,此后基本不变,其光降解保护作用明显优于β-CD包合物,具有更好的光降解联合保护作用。     

海藻酸钠纳米粒制备的研究进展

纳米粒药物载体能帮助药物靶向传输及可控释放,是生物医药领域的重要研究方向。海藻酸钠生物相容性好、易于修饰及加工形成微纳米颗粒,作为药物载体的应用研究日渐增多。综述了制备海藻酸钠纳米粒的4种方法,即离子交联法、乳化法、静电络合法和自组装法,并指出了4种方法的优缺点。     

基于疏水化修饰水溶性多糖的纳米粒制备及应用研究进展

疏水化修饰的水溶性聚合物，尤其是多糖，可以通过分子间和分子内的疏水部分之间得交联形成核．壳结构的自聚集纳米粒．纳米粒的制备方法分为超声法与乳化法两种．这类纳米粒是水凝胶基质含有大量水分，在液相中具有静态和动态的稳定性。相对于表面活性剂形成的胶束，多糖自聚集纳米粒在形成过程中具有很低的临界聚集浓度，其疏水微区由多条聚合物链构成并可形成多核结构。综述了以疏水化多糖为基质纳米粒的制备及应用研究状况．疏水化多糖纳米粒能够广泛的结合疏水性药物，有效的将药物靶向运输到病变组织，并保持较长时间的持续释放，提高了疏水药物的生物利用度：它可以通过疏水作用结合蛋白质，提高其抵御变性的能力并提高其热稳定性，还可以像“分子伴侣”一样可以预防蛋白质不可逆的变性聚集；同时它也可以通过离子相互作用与DNA结合，保护其不被机体内的各种酶降解，并能以有活性的形式将其释放出来，提高DNA的转染效率。这些结果显示出这类纳米粒在制药及生物技术领域良好的应用前景。     

New approaches to tumor therapy with siRNA-decorated and chitosan-modified PLGA nanoparticles

Abstract

Objective: In this study, we aimed to develop a candidate modifited polymeric nanoparticle (NP) system that will kill cancer cells by facilitated to apoptosis and also reduce pain.

Significance: The primary goal of treatment, especially for metastatic cancers, is to control the growth of the cancer and to alleviate the symptoms. Pain is one of the commonest symptoms of cancer. In cancer treatment, directing cancer cells to death while simultaneously relieving pain will be a new approach.

Methods: Chitosan-modified PLGA NPs were prepared using an nanoprecipitation technique. The NPs were loaded with flurbiprofen and decorated with folic acid. STAT3-siRNA was adsorbed to these polymeric NPs using antisense technology.

Results: The NPs were small in size (176.9–220.3?nm) with positive zeta potential (+14.1?mV to +27.2?mV). They had high loading capacity and prolonged release properties over 144 hours. Cytotoxicity studies performed with siRNA showed effective electrostatic interaction due to the positively charged NPs. Folic acid facilitated entry into cancer cells and helped to kill them.

Conclusion: The formulation we developed is a potential carrier system for both treatment of cancer and prevention of pain, especially for metastatic cancers.     

Standardized in vitro drug release test for colloidal drug carriers using modified USP dissolution apparatus I

Background: Recently the use of colloidal carriers as drug delivery systems is gaining more attention. Evaluation of the in vitro drug release is considered an important step during the development and quality control of such systems. Therefore, there is a need for a standard test technique to study in vitro drug release from colloidal systems. Methods: The glass basket dialysis method was performed by a modification to the USP dissolution apparatus I by replacing the baskets with glass cylinders closed at the lower end by dialysis membrane. This method was characterized for the essential test parameters and compared to the dialysis bags technique using different types of colloidal drug carriers, namely liposomes, polymeric, and lipid nanoparticles. Results: The method proved to be more discriminating than the conventional dialysis bag method and allowed for better comparison between different formulation parameters or experimental conditions. In general, the design is easy to perform, simple, and available in all pharmaceutical laboratories under the same setup. Conclusion: The described method is a step toward standardized dissolution tests on colloidal drug delivery systems and the possible comparability of results.     

A modified spontaneous emulsification solvent diffusion method for the preparation of curcumin-loaded PLGA nanoparticles with enhanced in vitro anti-tumor activity

To improve the anti-tumor activity of hydrophobic drug curcumin, we prepared curcumin-loaded PLGA nanoparticles （PLGA-Cur NPs） through a modified spontaneous emulsification solvent diffusion （modified-SESD） method. The influence of main preparation parameters was investigated, such as the volume ratio of binary organic solvents and the concentration of surfactant. Results indicated that the synthesized regular spherical PLGA NPs with the average diameter of 189.7 nm exhibited relatively higher yield （58.9%）, drug loading （11.0% （w/w）） and encapsulation efficiency （33.5%）, and also a controllable drug release profile. In order to evaluate the in vitro cytotoxicity of the prepared NPs, MTT assay was conducted, and results showed that the NPs could effectively inhibit HL60 and HepG2 cells with lower IC50 values compared with free curcumin. Furthermore, confocal microscopy together with flow cytometry analysis proved the enhanced apoptosis-inducing ability of PLGA-Cur NPs. Polymeric NP formulations are potential to be used for hydrophobic drug delivery systems in cancer therapy.     

壳聚糖修饰银纳米颗粒的制备及抗菌性能研究

采用液相化学还原法,以壳聚糖为修饰剂,硼氢化钠为还原剂,制备了壳聚糖修饰银纳米颗粒(chitosan-Ag NPs)。通过X射线粉末衍射仪、透射电子显微镜、傅立叶变换红外光谱仪等对所制备样品的结构和形貌进行了表征。结果表明,所制备纳米颗粒具有面心立方Ag的晶型结构,壳聚糖通过氨基和羟基中的N、O原子与Ag+的化学键合作用修饰在纳米颗粒表面,起到了限制颗粒粒径长大和防止其团聚的作用。采用肉汤连续稀释法检测了样品对大肠杆菌和金黄色葡萄球菌的抑菌杀菌性能,结果表明chitosan-Ag NPs具有优异的抗菌性,抗菌性能受到粒径大小的影响。     

乳糖酰化壳聚糖基自组装纳米载药体系的体外研究

制备乳糖酰化壳聚糖基自组装纳米微粒,用作抗肿瘤药物-甲氨喋呤(MTX)的载体,为肝靶向药物栽体系统的研究提供体外参考数椐.合成N-乳糖酰化-N-胆甾醇琥珀酰基壳聚糖(CLCS),并通过红外(IR)及核磁共振氢谱(1H NMR)对其进行结构确证.采用自组装的方法制备CLCS纳米微粒,并通过透射电镜及动态激光散射法对纳米微...     

壳聚糖修饰氧化铁磁性纳米颗粒的制备和性能研究

通过共沉淀法制备氧化铁磁性纳米颗粒,用壳聚糖对其表面进行修饰得到样品(CS@MNPs);表征其形貌结构、尺寸、表面基团、表面电荷、磁学性质和在不同介质中的稳定性等。实验结果表明,CS@MNPs具有典型的立方反尖晶石晶体结构;粒径为16.5nm;在生理(pH值7.4)条件下拥有较高的正电荷(10mV);呈现超顺磁性,对驰豫时间T1、T2,尤其是T2*具有很强的响应;在双蒸馏水和含10%新生牛血清的RPMI 1640培养液中具有良好的稳定性,具有作为磁共振造影剂的潜力。     

Synthesis,characterization and antibacterial activity of superparamagnetic nanoparticles modified with glycol chitosan

Iron oxide nanoparticles (IONPs) were synthesized by coprecipitation of iron salts in alkali media followed by coating with glycol chitosan (GC-coated IONPs). Both bare and GC-coated IONPs were subsequently characterized and evaluated for their antibacterial activity. Comparison of Fourier transform infrared spectra and thermogravimetric data of bare and GC-coated IONPs confirmed the presence of GC coating on IONPs. Magnetization curves showed that both bare and GC-coated IONPs are superparamagnetic and have saturation magnetizations of 70.3 and 59.8 emu g⁻¹, respectively. The IONP size was measured as ∼8–9 nm by transmission electron microscopy, and their crystal structure was assigned to magnetite from x-ray diffraction patterns. Both bare and GC-coated IONPs inhibited the growths of Escherichia coli ATCC 8739 and Salmonella enteritidis SE 01 bacteria better than the antibiotics linezolid and cefaclor, as evaluated by the agar dilution assay. GC-coated IONPs showed higher potency against E. coli O157:H7 and Staphylococcus aureus ATCC 10832 than bare IONPs. Given their biocompatibility and antibacterial properties, GC-coated IONPs are a potential nanomaterial for in vivo applications.     

Synthesis,characterization and antibacterial activity of superparamagnetic nanoparticles modified with glycol chitosan

Abstract

Iron oxide nanoparticles (IONPs) were synthesized by coprecipitation of iron salts in alkali media followed by coating with glycol chitosan (GC-coated IONPs). Both bare and GC-coated IONPs were subsequently characterized and evaluated for their antibacterial activity. Comparison of Fourier transform infrared spectra and thermogravimetric data of bare and GC-coated IONPs confirmed the presence of GC coating on IONPs. Magnetization curves showed that both bare and GC-coated IONPs are superparamagnetic and have saturation magnetizations of 70.3 and 59.8 emu g^?1, respectively. The IONP size was measured as ～8–9 nm by transmission electron microscopy, and their crystal structure was assigned to magnetite from x-ray diffraction patterns. Both bare and GC-coated IONPs inhibited the growths of Escherichia coli ATCC 8739 and Salmonella enteritidis SE 01 bacteria better than the antibiotics linezolid and cefaclor, as evaluated by the agar dilution assay. GC-coated IONPs showed higher potency against E. coli O157:H7 and Staphylococcus aureus ATCC 10832 than bare IONPs. Given their biocompatibility and antibacterial properties, GC-coated IONPs are a potential nanomaterial for in vivo applications.     

Preparation of chitosan/mesoporous silica nanoparticle composite hydrogels for sustained co-delivery of biomacromolecules and small chemical drugs

Abstract

We have developed composite hydrogels of chitosan (CS) and mesoporous silica nanoparticles (MSNs) in this study. The gelation rate, gel strength, drug delivery behavior and chondrocyte proliferation properties were investigated. The introduction of MSNs into CS accelerated the gelation process at body temperature and also increased the elastic modulus G′ from 1000 to 1800 Pa. When we used gentamicin (GS) and bovine serum albumin (BSA) as model small chemical drugs and biomacromolecules, respectively, the CS/MSN hydrogels released GS and BSA in a sustained manner simultaneously, but the CS hydrogels only showed sustained BSA release. Furthermore, in vitro chondrocyte culture showed that the CS/MSN composite hydrogels indeed performed much better in supporting chondrocyte growth and maintaining chondrocytic phenotype compared to the CS hydrogels. Therefore, the results suggest that the CS/MSN composite hydrogels can be potentially very useful for cartilage regeneration.     

Brain pharmacokinetics of neurotoxin-loaded PLA nanoparticles modified with chitosan after intranasal administration in awake rats

Context: Neurotoxin (NT), an analgesic peptide which was separated from the venom of Naja naja atra, is endowed an exceptional specificity of action that blocks transmission of the nerve impulse by binding to the acetylcholine receptor in the membrane. However, it has limited permeability across the blood-brain barrier (BBB).

Objective: The purpose of this study was to encapsulate NT within polylactic acid (PLA) nanoparticles (NPs) modified with chitosan (NT-PLA-cNPs) and to evaluate their brain pharmacokinetic behaviors after intranasal (i.n.) administration using a microdialysis technique in free-moving rats.

Methods: NT-PLA-cNPs (NT labeled with fluorescein isothiocyanate) were prepared and characterized. Then, NT-PLA-cNPs were i.n. administered to rats and the fluorescence intensity in the periaqueductal gray (PAG) was monitored for up to 480?min, with NT-PLA-NPs and NT solution as control groups.

Results: The NPs prepared were spherical with a homogenous size distribution. The mean particle size, zeta potential, and entrapment efficiency were 140.5?±?5.4?nm, +33.71?±?3.24 mV, and 83.51?±?2.65%, respectively. The brain transport results showed that T_max of NT-PLA-cNPs was equal with that of NT-PLA-NPs after i.n. administration (150?min). The C_max and AUC_{0–8 h} of each group followed the following order: NT-PLA-cNPs > NT-PLA-NPs. The corresponding absolute bioavailability (F_abs) of NT-PLA-cNPs was about 151% with NT-PLA-NPs as reference preparations.

Conclusion: These results suggest that NPs modified with chitosan have better brain targeting efficiency and are a promising approach for i.n. delivery of large hydrophilic peptides and proteins in improving the treatment of central nervous system (CNS) disorders.