Radiation synthesis of interpolymer polyelectrolyte complex and its application as a carrier for colon-specific drug delivery system

Novel pH-sensitive interpolymer polyelectrolyte complex was synthesized by gamma radiation-induced copolymerization of acrylic acid (AAc) and dimethyl aminoethyl methacrylate (DMAEMA). pH-dependent swelling showed different phase transitions depending on the copolymer composition and also showed the interpolymer polyelectrolyte complex formation at pH values ranged from pH 3 to pH 4. FT-IR and TGA was employed to study the complex formation. The influence of copolymer composition and pH value of the surrounding medium on the type of water diffusion in the glassy polymer was discussed. The ability of the prepared copolymer to be used as drug carrier for colon-specific drug delivery system was estimated using ketoprofen as a model drug.     

Frequency-controlled wireless shape memory polymer microactuator for drug delivery application

This paper reports the wireless Shape-Memory-Polymer actuator operated by external radio frequency magnetic fields and its application in a drug delivery device. The actuator is driven by a frequency-sensitive wireless resonant heater which is bonded directly to the Shape-Memory-Polymer and is activated only when the field frequency is tuned to the resonant frequency of heater. The heater is fabricated using a double-sided Cu-clad Polyimide with much simpler fabrication steps compared to previously reported methods. The actuation range of 140 μm as the tip opening distance is achieved at device temperature 44 °C in 30 s using 0.05 W RF power. A repeatability test shows that the actuator’s average maximum displacement is 110 μm and standard deviation of 12 μm. An experiment is conducted to demonstrate drug release with 5 μL of an acidic solution loaded in the reservoir and the device is immersed in DI water. The actuator is successfully operated in water through wireless activation. The acidic solution is released and diffused in water with an average release rate of 0.172 μL/min.     

Cadherin-integrated liposomes with potential application in a drug delivery system

N-cadherin (CDH2) proteins were reconstituted with liposomes using a baculovirus expression-liposome fusion method. CDH2 budded viruses were fused with giant liposomes containing dioleoylphophogycerol/dioleoylphosphatidylcholine (DOPG/DOPC) at pH 4.5 and the localization of CDH2 on the liposome membrane was observed by confocal laser scanning microscopy. CDH2 liposomes showed Ca(2+)-dependent association. CDH2-mediated association/dissociation in CDH2 liposomes was specific to Ca(2+) and reversible. CDH2-expressing LN-229 cells (human glioblastoma cell) adhered to CDH2 liposomes and small CDH2 liposomes (diameter approximately 150?nm), in particular, were internalized by endocytosis and partly escaped endosomes. Cadherin-containing liposomes show high potential as a new cell-specific proteoliposome. The baculovirus expression-liposome fusion method is useful as a new enabling technology for biomedical applications of functional proteoliposomes.     

自微乳释药系统提高药物生物利用度的机理与应用

全球大概有40％-70％的新的化学实体由于水溶性差而导致生物利用度低。对于这些化学实体而言,吸收的限速步骤是在胃肠道内的溶出。20世纪70年代,科研工作者们应用自微乳释药系统,以提高难溶性药物的溶出速率和生物利用度。自微乳化药物传递系统（self-microemulsifying drug delivery systems,SMEDDS）是由表面活性剂、油相、助表面活性剂有时还含有促过饱和物质等形成的固体或液体释药体系。     

9-硝基喜树碱叶酸聚合物胶束肿瘤靶向给药系统的表征及体外药效评价

背景：近年来,两亲性聚合物胶束作为难溶性药物载体和叶酸介导的肿瘤细胞靶向给药系统在药剂学研究领域受到极大的关注。 目的：制备包载9-硝基喜树碱的叶酸聚合物胶束并进行理化表征及体外药效评价。 方法：采用薄膜-水化法制得载药胶束,利用激光粒度分析仪检测胶束粒径大小,反相高效液相层析法检测载药量,透析法进行体外释放试验;利用肿瘤细胞摄取及体外生长抑制试验,对叶酸聚合物胶束作体外药效评价。 结果与结论：制得的9-硝基喜树碱叶酸聚合物胶束粒径为24~26 nm,载药量为3.24%,24 h累积释放百分率约90%。叶酸修饰的聚合物胶束对肿瘤细胞的亲和性及抗肿瘤活性显著高于普通胶束。提示叶酸修饰的聚合物胶束可为难溶性药物提供一种具有良好应用前景的肿瘤主动靶向纳米载药系统。     

Chitin/PLGA blend microspheres as a biodegradable drug delivery system: a new delivery system for protein

Novel chitin/PLGAs and chitin/PLA based microspheres were developed for the delivery of protein. These biodegradable microspheres were prepared by polymers blending and wet phase-inversion methods. The parameters such as selected non-solvents, temperature of water and ratio of polylactide to polyglycolide were adjusted to improve thermodynamic compatibility of individual polymer (chitin and PLGAs or chitin/PLA), which affects the hydration and degradation properties of the blend microspheres. Triphasic pattern of drug release model is observed from the release of protein from the chitin/PLGAs and chitin/PLA microspheres: the initially fast release (the first phase), the following slow release (the second phase) and the second burst release (the third phase). Formulations of the blends, which are based on the balance among the hydration rate of the chitin phase and degradation of chitin/PLA and PLGA phase, can lead to a controllable release of bovine serum albumin (BSA). In conclusion, such a chitin/PLGA 50/50 microsphere is novel and interesting, and may be used as a protein delivery system.     

聚合物囊泡作为药物载体的研究进展

聚合物囊泡作为一类新型的药物载体,具有独特优越的结构、性质和稳定性,可包载多种亲水、疏水性药物分子,已经成为当前分子自组装纳米药物载体的研究热点.论述了聚合物囊泡的结构和特点、制备方法与形成条件,介绍了形成聚合物囊泡的两亲聚合物类型及所形成的聚合物囊泡的特性,并对聚合物囊泡作为药物载体在诊断和治疗中的研究进展作一综述.     

A conductive nanostructured polymer electrodeposited on titanium as a controllable, local drug delivery platform

Infection and inflammation associated with orthopedic implants can be life threatening, time consuming, and expensive, thus, motivating the development of a local drug delivery platform that could prevent such deleterious events. For this purpose, nanostructured polypyrrole (PPy) incorporating antibiotics and anti-inflammatory drugs (penicillin/streptomycin (P/S) or dexamethasone (Dex), respectively) were coated on commercially pure titanium through an easy to use electrochemical deposition method. As shown in our previous study, about 80% (compared with initial amount) of these incorporated drugs were released after electrical stimulation spanning five cycles (voltage was varied between -1 V and 1 V). In a further continuation of this work, nanostructured P/S incorporated PPy coatings on titanium were demonstrated to be bactericidal against Staphylococcus epidermis after 1 h, and when incorporated with Dex, inhibited macrophage (an inflammatory and immune response cell) growth after 8 and 13 h of in vitro culture. Moreover, nanostructured PPy-drug films coated on titanium enhanced osteoblast (bone forming cells) proliferation, while at the same time, suppressed fibroblast (fibrous tissue forming cells) proliferation for up to 5 days. After electrical stimulation, antimicrobial and anti-inflammatory-coated devices yielded lower bacteria colonies and macrophage growth compared with unincorporated-drug PPy films (controls). This study, thus, suggests that drug incorporated nanostructured PPy coatings on titanium are capable of effectively treating potential orthopedic implant infection and inflammation, and lays the foundation for the further development of local and controllable on-demand drug delivery coatings to improve orthopedic implant efficacy.     

肝癌靶向载多烯紫杉醇聚多巴胺修饰琥珀酸酯-聚乳酸纳米粒子的研究

目的 建立一种简便的、具有肝癌靶向的聚多巴胺表面修饰聚合物纳米粒子以增加聚合物膜层和功能化的方法.方法 采用聚多巴胺修饰聚乙二醇1000-琥珀酸盐-聚乳酸纳米粒子(pD-TPGS-PLA/NPs),并用其包载多烯紫杉醇(DTX).为了达到靶向治疗肝癌的作用,再将半乳糖胺连接在pD-TPGS-PLA/NPs表面,从而通过配体-受体介导的作用提高DTX的递送效率.结果 聚多巴胺-琥珀酸酯-聚乳酸纳米粒子(pD-TPGS-PLA/NPs)和半乳糖胺-聚多巴胺-琥珀酸酯-聚乳酸纳米粒子(Gal-pD-TPGS-PLA/NPs)在粒径和形态学上与琥珀酸酯-聚乳酸纳米粒子(TPGS-PLA/NPs)有明显的不同.体外研究结果显示,TPGS-PLA/NPs、pD-TPGS-PLA/NPs和Gal-pD-TPGS-PLA/NPs对DTX有相似的释放行为.激光扫描共聚焦显微镜和流式细胞仪结果显示,HepG2细胞对于包载香豆素-6的Gal-pD-TPGS-PLA/NPs有较高地细胞摄取效率.相比于TPGS-PLA/NPs、pD-TPGS-PLA/NPs和临床应用的DTX药物多西他赛,载DTX的Gal-pD-TPGS-PLMNPs对HepG2细胞的生长有更强的抑制能力.体内抗肿瘤研究结果显示,在荷瘤裸鼠上注射包载DTX的Gal-pD-TPGS-PLA/NPs能有效减小肿瘤尺寸.结论 Gal-pD-TPGS-PLA/NPs可通过配体-受体识别与肝癌细胞发生特有的相互作用,有望成为一种极具潜力的靶向治疗肝癌的药物递送系统.     

磷酸钙骨水泥药物缓释载体研究进展

本文综述了磷酸钙骨水泥作为药物缓释载体系统在载药前后的特征变化、药物缓释的动力学曲线及其影响因素 ,阐明该系统在临床骨缺损修复中具有一定的应用价值     

Bioactive glass as a drug delivery system of tetracycline and tetracycline associated with beta-cyclodextrin

The aim of this study was to evaluate the physical-chemical properties, in vivo biocompatibility and antimicrobial activity of bioactive glasses (BG) used as a controlled release device for tetracycline hydrochloride and an inclusion complex formed by tetracycline and beta-cyclodextrin at 1:1 molar ratio. The BG as well as their compounds loaded with tetracycline (BT) and tetracycline:beta-cyclodextrin (BTC) were characterized by FTIR spectroscopy, X-ray powder diffraction, differential scanning calorimetry and by scanning electron microscopy and energy dispersive spectroscopy. The in vivo test was carried out with female mice split into three groups treated with bioactive glass either without drugs, or associated with tetracycline, or with tetracycline:beta-cyclodextrin by subcutaneous implantation. The histological examination of tissue at the site of implantation showed moderate inflammatory reactions in all groups after 72 h. The bacterial effect was tested on A. actinomycetemcomitans suspended in BHI broth, with or without bioactive particles. A considerable bacteriostatic activity was found with BT and BTC glasses, as compared to plain glass. The presence of cyclodextrin was important to slow down the release of tetracycline for a long period of time and it was verified that the presence of tetracycline or its inclusion complex, tetracycline:beta-cyclodextrin, did not affect the bioactivity of the glass.     

Alginate and chitosan particles as drug delivery system for cell therapy

Drug-carrying microstructures which have a size similar to biological structures are very attractive to encapsulate drugs and protect them during the transit in the human body. This paper describes polymeric (alginate and chitosan) particles (average radius 500 nm) produced by homogenization techniques. In vitro studies performed on cell lines demonstrate the effectiveness of such particles for intracellular drug delivery. Our experiments suggest that cellular up - take increases linearly with particle concentration in the growth medium, and the internalization process has a first order kinetics (characteristic time around 0.5 h⁻¹). In addition, the particles degrade within 24 h from the up-take without side effects for cell viability.     

Micro-fabricated perforated polymer devices for long-term drug delivery

Fabrication techniques have been developed to produce a perforated polymer microtube as a drug delivery device. The technique consists of first forming a silicon platform with trenches and alignment marks to hold the tubes for subsequent processing. Photolithography and reactive ion etching with an inductively coupled plasma source were used to fabricate micro holes on the surface of polyimide tubes. Several materials have been used to form the etching mask, including titanium film deposited by e-beam evaporation and SiO₂ and SiN_x films deposited by high-density plasma chemical vapor deposition (HDPCVD). Three equidistant holes of 20 μm in diameter were fabricated on polyimide tubes (I.D. = 125 μm). The perforated tubes were loaded with ethinyl estradiol and tested for drug release in phosphate buffered saline (pH = 7.1) at 37°C. Zero order release was observed over a period of 30 days with a potential to be extended to 4 years.     

Iontophoretic drug delivery system: a review.

Among the recent developments in the field of transdermal drug delivery, iontophoresis has emerged as a very promising tool for this purpose. Various studies have been performed on drug delivery through the skin using electric current. Iontophoresis has thereby been found to be effective in particular in transdermal protein and peptide drug delivery. This article reviews the principle, potential benefits, and applications of drug delivery based on iontophoresis. It focuses furthermore on current research and future trends in the field of iontophoretic drug delivery.     

Synthesis and characterization of pH-sensitive dextran hydrogels as a potential colon-specific drug delivery system.

pH-Sensitive dextran hydrogels were prepared by activation of dextran (T-70) with 4-nitrophenyl chloroformate, followed by conjugation of the activated dextran with 4-aminobutyric acid and cross-linking with 1,10-diaminodecane. The cross-linking efficiencies determined by mechanical measurements were in the range of 52-63%. Incorporation of carboxylpropyl groups in dextran hydrogels led to a higher equilibrium and faster swelling under high pH conditions. The swelling reversibility of hydrogels was also observed after repeated changes in buffers between pH 2.0 and 7.4. The slow rates of swelling and deswelling in response to changes in pH were attributed to the hydrophilic nature of dextran and formation of hydrogen bonds between the hydroxyl groups of dextran with water molecules. The pronounced effect of carboxylic acid content on degradation of hydrogels was observed after 4 h of incubation with dextranase and the influence significantly decreased after exposure to the enzyme for 8 h. The mechanism of bulk degradation of hydrogels under high swelling extent was substantiated using Coomassie blue protein assay. The release rate of bovine serum albumin from hydrogels was primarily determined by the swelling extent. The release rate was further enhanced by addition of dextranase in buffer solutions.     

Poly(2-hydroxyethyl methacrylate) film as a drug delivery system for pilocarpine

This work investigates pilocarpine trapped in a matrix diffusion-controlled drug delivery system using hydrophilic inserts of Poly(2-hydroxyethyl methacrylate) (pHEMA) to ensure an increased bioavailability of pilocarpine and prolong the length of time in which the medication remains in the eyes of the test subjects. The physical and chemical properties of pilocarpine were investigated to elucidate the mechanism of drug-polymer interaction and the effect on drug release behavior of controlled release polymeric devices. In vitro release studies indicated that pilocarpine continued to be released from the inserts for a 24 h period. The results of intraocular pressure tests performed on albino rabbits were consistent with the observed in vitro behavior. The pressure decrease was significant for a period longer than 48 h. It confirms that the inserts, as sustainable releasing devices, are promising carriers for ophthalmic drug delivery systems.     

纳米粒子作为药物输送和药物控释体系的应用前景

纳米粒子作为药物和基因的载体显现出极大的潜力并被广泛研究。纳米粒子的超微小体积可使药物输送智能化,例如靶向定位地将药物投递到病灶局部或专一性地作用于靶细胞。纳米粒子的载体材料可屏蔽药物不良气味、维持药物长期缓慢释放、延长药物半衰期和减小毒副作用等。本文将从纳米药物输送、控释制剂的制备和应用前景等方面进行综述。     

Microcapsules as drug delivery devices

This review will deal with techniques for producing drug-filled microcapsules, current applications of such microcapsules, and projected applications of microcapsules as drug delivery devices. Specific encapsulation techniques to be evaluated include coacervation, solvent evaporation, interfacial polymerization, emulsion, and hot melt processes. Selection of capsule coating materials will be another factor considered. Differences in specific design requirements of capsules to be administered i.v., i.m. (or s.c./i.p.), and orally will be discussed at length. Specific examples of current capsules administered by each of the routes will be given.     

Nanocapsules as drug delivery systems

Dispersed polymer nanocapsules can serve as nano-sized drug carriers to achieve controlled release as well as efficient drug targeting. The dispersion stability and the primary physiological response are mainly determined by the type of the surfactant and the nature of the outer coating. Their release and degradation properties largely depend on the composition and the structure of the capsule walls. Another important criterion is the capsule size, where an optimum is generally seen for radii ranging between 100 and 500 nm. Nanocapsules can be prepared by four principally different approaches: interfacial polymerization, interfacial precipitation, interfacial deposition, and self assembly procedures. All these procedures offer their individual advantages and disadvantages when it comes to the design of optimized drug carrier systems. The most important capsule parameters such as capsule radius distribution, the capsule surface, the thickness and the permeability of the capsule membrane and its thermal or chemical decomposition, are discussed and examples are shown. In combination with efficient preparation procedures, nanocapsule dispersions allow for new and promising approaches in many kinds of pharmaceutical therapies.