磁靶向给药体系及磁性纳米材料的制备与表征

磁靶向给药体系能有效减小化疗药物的毒副作用，提高药效，减少用药量，为癌症肿瘤的靶向治疗提供了一个新的途径。磁性靶向抗癌药物体系主要由纳米级磁性材料、骨架材料、化疗药物组成。其结构可以分为包埋型和偶联型：前者是将药物和磁性纳米材料包埋、分散在高分子基质中；后者是将药物通过某种作用力偶联在磁性高分子微球的表面。尽管磁靶向药物的研究已经取得了很大的进展，但是目前还存在着诸如药物载体的生物相容性、靶向功能单一和药物释放缺乏控制等一系列的问题，并且主要集中在包埋型的制备和研究，药物在输送到病灶的过程中会产生一系列的副反应，在将来的临床应用中受到很大的限制。而偶联型磁靶向给药体系的药物释放既可以达到空间控制的效果，也可以起到一定的时间控制的作用。磁性纳米材料不仅是磁靶向给药体系制备的基础，并且在细胞分离，固定化酶，核酸杂交等生物领域和磁记录、吸波材料等方面有广泛的应用。本论文以此为立题依据，共分为七个部分。第一至第四部分以共沉淀法制备的具有超顺磁性的Fe3O4纳米粒子为磁核，选择能生物降解且无毒的无机材料二氧化硅、天然高分子壳聚糖和人工合成的高分子聚乳酸为包覆材料，常用的抗癌药阿霉素、甲氨喋呤为模型药物，制备了三个偶联型磁靶向给药体系，对其体外药物释放行为及磁学性质进行了测定；第五部分结合生物医药对Fe3O4纳米粒子的应用要求，提出了一种简单制备粒径可控的单分散性的亲油/亲水性Fe3O4纳米粒子的新方法, 同时还探讨了亲油/亲水性Fe3O4纳米粒子的可能形成过程；第六部分将阿霉素以酰胺键接枝在可降解高分子材料P3HB4HB上，将得到的P3HBP4HB－DOX偶联物和第五部分所制备的亲油性Fe3O4纳米粒子共混于氯仿中进行静电纺丝，成功地制备了载有DOX的磁性纤维，改变了以往磁靶向给药体系的单一微球形貌；第七部分以EDTA和FeCl2为原料，采用水热法制备了十二面体四氧化三铁纳米粒子，探讨了EDTA和FeCl2的摩尔比、反应温度、反应时间和反应介质对产物形貌的影响，并提出了这一新颖形貌的可能形成机理。

Precursor Film in Dynamic Wetting, Electrowetting, and Electro-Elasto-Capillarity

Dynamic wetting and electrowetting are explored using molecular dynamics simulations. The propagation of the precursor film (PF) is fast and obeys the power law with respect to time. Against the former studies, we find the PF is no slip and solidlike. As an important application of the PF, the electro-elasto-capillarity, which is a good candidate for drug delivery at the micro- or nanoscale, is simulated and realized for the first time. Our findings may be one of the answers to the Huh-Scriven paradox and expand our knowledge of dynamic wetting and electrowetting.

Experimental study of Electro-elasto-capillarity:Electric field driven unwrapping of water drop with elastic film

<正>Elasto-capillarity has drawn much of scientists' attention in the past several years.By inducing electric field into the droplet,the encapsulation and release procedure can be realized and we call it electro-elasto-capillarity(EEC).EEC offers a novel method for micro-scale actuation and self-assemble of moveable devices.It also provides a good candidate for the drug delivery at micro- or nanoscale.

Swelling behaviour of alginate-chitosan microcapsules prepared by external gelation or internal gelation technology

Swelling behaviour is one of the important properties for microcapsules made by hydrogels, which always affects the diffusion and release of drugs when the microcapsules are applied in drug delivery systems. In this paper, alginate-chitosan microcapsules were prepared by different technologies called external or internal gelation process respectively. With the volume swelling degree (S-w) as an index, the effect of properties of chitosan on the swelling behaviour of both microcapsules was investigated. It was demonstrated that the microcapsules with low molecular weight and high concentration of chitosan gave rise to low S-w. Considering the need of maintaining drug activity and drug loading, neutral pH and short gelation time were favorable. It was also noticed that S-w of internal gelation microcapsules was lower than that of external gelation microcapsules, which was interpreted by the structure analysis of internal or external gelation Ca-alginate beads with the aid of confocal laser scanning microscope. (C) 2004 Elsevier Ltd. All rights reserved.

Preparation of uniform calcium alginate gel beads by membrane emulsification coupled with internal gelation

With the objective of making calcium alginate gel beads with small and uniform size, membrane emulsification coupled with internal gelation was proposed. Spherical gel beads with mean size of about 50 mum, and even smaller ones in water, and with narrow size distribution were successfully obtained. Experimental studies focusing mainly on the effect of process parameters on bead properties were performed. The size of the beads was mainly dependent on the diameter of the membrane pores. High transmembrane pressure made for large gel beads with wide size distribution. Low sodium alginate concentration produced nonspherical beads, whereas a high concentration was unsuitable for the production of small beads with narrow distribution. Thus 1.5% w/v was enough. A high surfactant concentration favored the formation of small beads, but the adverse effect on mass transfer should be considered in this novel process. (C) 2002 Wiley Periodicals, Inc.

Biodegradable Interpolyelectrolyte Complexes Based on Methoxy Poly(ethylene glycol)-b-poly(alpha,L-glutamic acid) and Chitosan

We synthesized methoxy poly(ethylene glycol)-b-poly(alpha,L-glutamic acid) (mPEGGA) diblock copolymer by ring-opening polymerization of N-carboxy anhydride of gamma-benzyl-L-glutamate (NCA) using amino-terminated methoxy polyethylene glycol (mPEG) as macroinitiator. Polyelectrolyte complexation between mPEGGA as neutral-block-polyanion and chitosan (CS) as polycation has been scrutinized in aqueous solution as well as in the solid state.

Glutathione-Mediated Release of Functional Plasmid DNA from Positively Charged Quantum Dots

DNA was efficiently bound to water-soluble positively charged CdTe quantum dots (QDs) through complementary electrostatic interaction. These QDs-DNA complexes were disrupted and DNA was released by glutathione (GSH) at intracellular concentrations. Interestingly, there was almost no detectable DNA released by extracellular concentration of GSH. The formation of QDs-DNA complexes and GSH-mediated DNA release from the complexes were confirmed by dye displacement assay, electrophoretic mobility shift assay (EMSA), transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) experiments.

Effect of binary block-selective solvents on self-assembly of ABA triblock copolymer in dilute solution

We have studied the self-assembly of the ABA triblock copolymer (P4VP-b-PS-b-P4VP) in dilute solution by using binary block-selective solvents, that is, water and methanol. The triblock copolymer was first dissolved in dioxane to form a homogeneous solution. Subsequently, a given volume of selective solvent was added slowly to the solution to induce self-assembly of the copolymer. It was found that the copolymer (P4VP(43)-b-PS366-b-P4VP(43)) tended to form spherical aggregate or bilayer structure when we used methanol or water as the single selective solvent, respectively.

Biodegradable amphiphilic block copolymers bearing protected hydroxyl groups: Synthesis and characterization

A new biodegradable amphiphilic block copolymer, poly(ethylene glycol)-b-poly(L-factide-co-9-phenyl-2,4,8, 10-tetraoxaspiro[5,5]undecan-3-one) [PEG-b-P(LA-co-PTO)], was successfully prepared by ring-opening polymerization (ROP) Of L-lactide (LA) and functionalized carbonate monomer 9-phenyl-2,4,8,10-tetraozaspiro[5,5]undecan-3-one (PTO) in the presence of monohydroxyl poly(ethylene glycol) as macroinitiator using Sn(Oct)(2) as catalyst. NMR, FT-IR, and GPC studies confirmed the copolymer structure.

Novel aliphatic poly(ester-carhonate) with pendant allyl ester groups and its folic acid functionalization

A series of novel poly(ester-carbonate)s bearing pendant allyl ester groups P(LA-co-MAC)s were prepared by ring-opening copolymerization Of L-lactide (LA) and 5-methyl-5-allyloxycarbonyl-1,3-dioxan-2-one (MAC) with diethyl zinc (ZnEt2) as initiator. NMR analysis investigated the microstructure of the copolymer. DSC results indicated that the copolymers displayed a single glass-transition temperature (T-g), which was indicative of a random copolymer, and the Tg decreased with increasing carbonate content in the copolymer.

Novel pH- and temperature-responsive block copolymers with tunable pH-responsive range

A series of novel pH- and temperature-responsive diblock copolymers composed of poly(N-isopropylacrylamide) (PNIPAM) and poly[(L-glutamic acid)-co-(gamma-benzyl L-glutamate)] [P(GA-co-BLG)] were prepared. The influence of hydrophobic benzyl groups on the phase transition of the copolymers was studied for the first time. With increasing BLG content in P(GA-co-BLG) block, the thermal phase transition of the diblock copolymer became sharper at a designated pH and the critical curve of phase diagram of the diblock copolymer shifted to a higher pH region.

Electroactive Aniline Pentamer Cross-Linking Chitosan for Stimulation Growth of Electrically Sensitive Cells

A new kind of electroactive polymers was synthesized by using aniline pentamer (AP) cross-linking chitosan (CS) in acetic acid/DMSO/DMF solution. UV-vis and CV confirmed the electroactivity of polymers in acidic aqueous solution. The amphiphilic polymers self-assembled into 200-300 nm micelles by dialysis against deionized water from the acetic acid buffer solution. Three samples with different weight percentages of AP were used to identify the relationship between the content of AP and the differentiation of rat neuronal pheochromocytoma PC-12 cells without external stimulation.

The release behavior of doxorubicin hydrochloride from medicated fibers prepared by emulsion-electrospinning

The release behavior of a water-soluble small molecule drug from the drug-loaded nanofibers prepared by emulsion-electrospinning was investigated. Doxorubicin hydrochloride (Dox), a water-soluble anticancer agent, was used as the model drug. The laser scanning confocal microscopic images indicated that the drug was well incorporated into amphiphilic poly(ethylene glycol)-poly(L-lactic acid) (PEG-PLA) diblock copolymer nanofibers, forming "core-sheath" structured drug-loaded nanofibers.

Amphiphilic Core-Shell Nanocarriers Based On Hyperbranched Poly(ester amide)-star-PCL: Synthesis, Characterization, and Potential as Efficient Phase Transfer Agent

Amphiphilic biodegradable star-shaped polymer was conveniently prepared by the Sn(Oct)(2)-catalyzed ring opening polymerization of c-caprolactone (CL) with hyperbranched poly(ester amide) (PEA) as a macroinitiator. Various monomer/initiator ratios were employed to vary the length of the PCL arms. H-1 NMR and FTIR characterizations showed the successful synthesis of star polymer with high initiation efficiency. SEC analysis using triple detectors, RI, light scattering, and viscosity confirmed the controlled manner of polymerization and the star architecture.