Release characteristics of polymethacrylate nanospheres containing coumarin-6

Sustained release nanospheres were prepared from the polymethacrylates Eudragit^r` S₁₀₀ and E₁₀₀ containing a water insoluble dye by a salting-out method. Coumarin-6 was used as a model for insoluble analgesics to ascertain uptake and release properties dependent on polymer characteristics and pH. Morphology and particle size were characterized by scanning electron microscopy (SEM). Particles were smooth, spherical and uniform with diameters ranging from 0.6–0.8 μm. Yield was 38% and 86% for E₁₀₀and S₁₀₀, respectively, and encapsulation of coumarin-6 efficiency was 58% and 75%, respectively. Coumarin-6 was stable within the polymer matrix at temperatures from -20$C to 45$C for 4 months. Release was most efficient from S₁₀₀ polymers in phosphate buffer at pH 7.4 and 8.0 reaching a maximum ～ 5 hours prior to samples at pH 7.0 and 9.0. Release was biphasic and concentration as a function of the square root of time produced linear data suggesting a Higuchi type diffusion from a polymer matrix. Release from E₁₀₀ was 65% lower than that from S₁₀₀ and was not solely dependent upon the ionization of polymer but most likely due to a combination of factors including buffer ionization.     

重组人骨形态发生蛋白-2壳聚糖纳米微球的制备及检测

目的 制备负载重组人骨形态发生蛋白-2(rhBMP-2)壳聚糖纳米微球,并检测其粒径、形态、降解及药理特性,以评估壳聚糖纳米微球作为rhBMP-2缓释载体的可行性.方法 以壳聚糖为原料、三聚磷酸钠为交联剂,通过离子交联法制备负载rhBMP-2壳聚糖纳米微球,应用透视电镜观察微球的形态、激光粒径,分析其粒径分布、溶菌酶降解,了解降解特性.通过酶联免疫吸附实验(ELISA)检测rhBMP-2壳聚糖微球的载药率、包封率和释药规律.结果 离子交联法制备的壳聚糖纳米微球,平均粒径大小为230nm,成球性较好,包封率和载药率分别为(66.867±4.575)％、(33.437±2.290)μg/mg;体外释药试验rhBMP-2可以从壳聚糖纳米微球中缓慢释放,释放行为符合双向动力学规律,整个释放过程可达30 d.结论 离子交联法可成功制备壳聚糖纳米微球并具有缓释rhBMP-2的能力,为进一步应用于骨组织工程研究提供实验依据.     

三氧化二砷免疫毫微球的制备及活性检测

目的 制备单抗BDI-1导向的三氧化二砷免疫蛋白微球[As2O3-(BSA-NS)-BDI-1]并检测其特异性结合膀胱肿瘤细胞的活性。方法 通过蛋白交联固化及N一羟基琥珀酰亚胺基-3-(2-吡基二硫)-丙酸脂(SPDP)交联的方法制备蛋白免疫微球。还原电泳、光镜和电镜的方法鉴定As2O3，免疫微球的共价连接与活性。吖啶橙染色检测肿瘤细胞凋亡。结果还原电泳可见免疫微球被还原后在远端形成两条蛋白条带。光镜下可见蛋白微球在肿瘤细胞周围并随细胞移动。电镜下可见蛋白微球与肿瘤细胞紧密连接且形态完整。吖啶橙染色可见免疫微球处理的膀胱肿瘤细胞表现出凋亡特征。结论 制备的As2O3-(BSA-NS)-BDI-1由共价键连接且能特异性的结合膀胱肿瘤细胞BIU-87而发挥诱导凋亡的作用。     

两性霉素B/聚乙二醇-聚谷氨酸苄酯纳米球溶血毒性的研究

目的:考察两性霉素B/聚乙二醇-聚谷氨酸(AmB/PEG-PBLG)纳米球是否能降低AmB的溶血毒性.方法:超微透析法制备AmB/PEG-PBLG纳米药球,用紫外分光光度法测定样品的溶血率.结果:AmB/PEG-PBLG纳米药球平均粒径142.1 nm,载药量27.55%;溶血率从低到高依次为:PEG-PBLG空白纳米球、脱氧胆酸钠、AmB/PEG-PBLG纳米药球、AmB注射液.结论:AmB/PEG-PBLG纳米药球能有效降低AmB的溶血毒性.     

Material properties in complement activation

Uncontrolled complement activation can induce many inflammatory and life threatening conditions. Accordingly, the role of complement in initiation of adverse reactions to polymers and nanoparticulate drug carriers is receiving increasing attention and has prompted extensive ‘structure-immune performance’ relationship studies in nanomedicine research at many fronts. The interaction between nanomaterials and the complement system is complex and regulated by inter-related factors that include nanoscale size, morphology and surface characteristics. Each of these parameters may affect complement activation differently and through different sensing molecules and initiation pathways. The importance of material properties in triggering complement is considered and mechanistic aspects discussed. Mechanistic understanding of complement events could provide rational approaches for improved material design and nanoengineering strategies for clinical medicine.     

Quantitative multi-agent models for simulating protein release from PLGA bioerodible nano- and microspheres

Using poly(lactide-co-glycolide) (PLGA) particles for drug encapsulation and delivery has recently gained considerable popularity for a number of reasons. An advantage in one sense, but a drawback of PLGA use in another, is that drug delivery systems made of this material can provide a wide range of dissolution profiles, due to their internal structure and properties related to particles' manufacture. The advantages of enriching particulate drug design experimentation with computer models, are evident with simulations used to predict and optimize design, as well as indicate choice of best manufacturing parameters. In the present work, we seek to understand the phenomena observed for PLGA micro- and nanospheres, through Cellular Automata (CA) agent-based Monte Carlo (MC) models. Systems are studied both over large temporal scales (capturing slow erosion of PLGA) and for various spatial configurations (capturing initial as well as dynamic morphology). The major strength of this multi-agent approach is to observe dissolution directly, by monitoring the emergent behaviour: the dissolution profile manifested, as a sphere erodes. Different problematic aspects of the modelling process are discussed in details in this paper. The models were tested on experimental data from literature, demonstrating very good performance. Quantitative discussion is provided throughout the text in order to make a demonstration of the use in practice of the proposed model.     

Polyelectrolyte biomaterial interactions provide nanoparticulate carrier for oral insulin delivery

Nanospheres are being developed for the oral delivery of peptide-based drugs such as insulin. Mucoadhesive, biodegradable, biocompatible, and acid-protective biomaterials are described using a combination of natural polyelectrolytes, with particles formulated through nanoemulsion dispersion followed by triggered in situ gel complexation. Biomaterials meeting these criteria include alginate, dextran, chitosan, and albumin in which alginate/dextran forms the core matrix complexed with chitosan and albumin coat. Smaller size and higher albumin-based acid-protective formulation was orally administered to diabetic rats and glucose reduction and physiological response analyzed. Insulin encapsulation efficiency was 90, 82, and 66% for uncoated, chitosan-coated, and albumin-chitosan-coated alginate nanospheres, respectively. The choice of coating polymer seems to influence insulin release profile and to be crucial to prevent peptic digestion. Physiological response following oral delivery showed that insulin albumin-chitosan-coated alginate nanospheres reduced glycemia ∼ 72% of basal values. Albumin serves as an important enteric coating providing acid- and protease protection enabling uptake of active drug following oral dosage.     

脂质微泡与PLGA纳米粒复合体的制备原理分析

目的制备一种连接有PLGA纳米粒的新型脂质超声微泡并分析其制备原理。方法采用碳二亚胺法,并结合静电吸附,使表面带有氨基和正（或负）电荷的脂质微泡与表面带（或不带）有活化羧基的PLGA纳米粒进行缩合偶联反应,通过普通光学显微镜和荧光显微镜观察两者结合情况。结果普通光镜与荧光显微镜下观察,表面带正电荷的脂质微泡与活化羧基的PLGA纳米粒可以成功偶联,PLGA纳米粒结合于脂质微泡表面;而表面带负电荷的脂质微泡与活化羧基的PLGA纳米粒以及表面带正电荷的脂质微泡与未活化羧基的高分子聚合物纳米粒均未见结合。结论化学共价偶联与静电吸附协同作用有利于促成脂质微泡与PLGA纳米粒的有效连接,而两者单用均不能产生连接。     

Cyclophosphamide-loaded nanospheres: analysis of the matrix structure by thermal and spectroscopic methods

This study reports on the preparation and evaluation of cyclophosphamide loaded-polyalkylcyanoacrylate nanospheres obtained by emulsion polymerization. Characterization by differential scanning calorimetry, infrared spectroscopy and X-ray diffraction can reveal state dispersion of the drug inside the nanospheres. Such information predicts the stability of the particles and the drug release behaviour. The study has indicated the prescence of a molecular dispersed system. The drug release behaviour was also studied.     

bFGF聚乳酸纳米微球对兔成骨细胞增殖的影响

目的：观察碱性成纤维生长因子聚乳酸纳米微球缓释系统（bFGF—PLA—Ns）对体外培养的兔成骨细胞的增殖影响。方法：体外培养兔成骨细胞并鉴定，将bFGF—PLA—Ns和成骨细胞一起培养，采用MTr法检测微球对成骨细胞增殖状况的影响，免疫组化检测增殖细胞核抗原（PCNA）在成骨细胞中表达，并与单纯bFGF的作用进行比较。结果：bFGF—PLA—Ns具有良好的生物活性，能显著促进兔成骨细胞的增殖，其效应高于单纯施加bFGF的效应。结论：制备的bFGF—PLA—Ns比单纯的bFGF有更为显著的生物学效应，在骨创伤的治疗中有良好的前景。