Comparison of in vitro and in vivo acoustic response of a novel 50:50 PLGA contrast agent

A comparison between in vitro and in vivo experiments conducted to investigate the acoustic properties of a novel, 1.2 μm diameter poly(lactic-co-glycolic acid) (50:50) (PLGA) ultrasound contrast agent, the development of which was described previously by us, is presented. A pulse-echo setup was used to determine enhancement in vitro. Additional in vitro studies further characterized the hollow microcapsules, including resonance frequency from attenuation measurements (from 2.25 to 15 MHz) and temperature effects (25 °C vs. 37 °C). In vivo, four rabbits received intravenous injections of the agent (dose range: 0.005–0.13 ml/kg). Quantitative in vivo dose–responses were calculated off-line using spectral power analysis of audio Doppler signals acquired from a custom-made 10 MHz cuff transducer placed around the surgically exposed distal aorta. This frequency was chosen since the very shallow scanning depths encountered in rabbits, in particular for the cuff transducer placed directly around the vessel, necessitates the use of high frequency imaging devices with sufficient spatial resolution to enable meaningful measurements. For qualitative assessments, two rabbits were imaged pre- and post-contrast administration (dose: 0.1 ml/kg) in power Doppler mode. Significant acoustic enhancements (up to 24 dB) were reported both in vitro and in vivo. Moreover, the rabbits did not show any adverse side effects from multiple injections (>20) of the agent. Measured in vitro resonance frequency between 3.09 and 3.49 MHz was lower than predicted for a similar sized free bubble, potentially due to capsule wall structure. Minimal loss of signal (4 dB) was observed at 25 °C over 20 min of insonation at 5 MHz but at 37 °C the signal dropped close to base line within the first 5 min. This temperature sensitivity could be due to loss of capsule integrity (and hence loss of gas). Potential causes include increased hydrolysis or polymer softening and increased water uptake by the shell at temperatures closer to the glass transition temperature (T_g).     

Glucose-Sensitive Nanoassemblies Comprising Affinity-Binding Complexes Trapped in Fuzzy Microshells

A new design for glucose monitoring with "smart" materials based on self assembly, competitive binding, and resonance energy transfer (RET) is presented. The basic transduction principle is changing RET efficiency from fluorescein isothiocyanate (FITC) to tetramethylrhodamine isothiocyanate (TRITC), as FITC-dextran is displaced from TRITC-Concanavalin A (Con A) with the addition of glucose. Nanoscale fabrication by self-assembly of Con A/dextran into multilayer films, followed by polymer multilayers. The advantages of this approach include physical localization and separation of sensing molecules from the environment via entrapment of the biosensorelements in a semi-permeable polymeric shell, and only functional molecules are included in the sensors. To realize these nanostructures, dissolvable resin microparticles were coated with FITC-dextran+TRITC-Con A multilayers, followed by polyelectrolyte multilayers, and the core particles were then dissolved to yield hollow capsules. The nanoassembly process was studied using microbalance mass measurements, fluorescence spectroscopy, confocal fluorescence microscopy, and zeta-potential measurements. The key findings are that the specific binding between Con A and dextran can be used to deposit ultrathin multilayer films, and these exhibit changing RET in response to glucose. Fluorescence spectra of a microcapsules exhibited a linear, glucose-specific, 27% increase in the relative fluorescence of FITC over the 0-1800 mg/dL range. These findings demonstrate the feasibility of using self-assembled microcapsules as optical glucose sensors, and serve as a basis for work toward better understanding the properties of these novel materials.     

Novel ultrasound contrast agents

As a novel ultrasound diagnostic contrast agent, the preparation, characterization and ultrasound imaging in the body of dog about poly(lactic acid) (PLLA) microcapsules have been studied. The behavior of this kind of contrast agent in the microcirculation was also investigated. Prepared by (water/oil/water) emulsion-solvent evaporation protocol, the PLLA microcapsules with hollow structure can enhance the ultrasound image both in vitro and in vivo, and the enduring time can last as long as 3 h. The microcirculation examination shows that the PLLA microcapsules with a diameter ranging from 2 to 8 μm could pass through the pulmonary capillaries without retention. All the results prove the PLLA microcapsules for potential use for the clinical application.     

药物控制释放方法

药物控制释放方法是目前药物学发展的一个重要领域，本文从贮库型和基质型两方面较为详细地综述了高分子药物控制释放的方法。     

Phospholipase A2 hydrolysis of mixed phospholipid vesicles formed on polyelectrolyte hollow capsules

Mixtures of the phospholipids L-alpha-dimyristoylphosphatidic acid (DMPA) and L-alpha-dipalmitoylphosphatidylcholine (DPPC) have been successfully adsorbed onto the charged surface of multilayer polyelectrolyte capsules to form a novel vesicle. Leaving such vesicles in phospholipase A(2) solution, we observed the hydrolysis reaction on the surface of the lipid/polymer vesicles and a permeability change before and after the reaction by confocal-laser scanning microscopy (CLSM). A capsule with adjustable permeability was constructed. This method may provide new features for drug-release vesicles.     

Neuron cells uptake of polymeric microcapsules and subsequent intracellular release

Neuron cells uptake of biodegradable and synthetic polymeric microcapsules functionalized with aggregates of gold nanoparticles incorporated into their shells is demonstrated in situ. In addition to traditionally used optical microscopy, electron microscopy is used both for higher-resolution imaging and for confirming the uptake by focused ion beam cross-sectioning of specific cells in situ. Subsequently, physical methods of release are compared to chemical methods wherein laser-induced intracellular release of dextran molecules into the cytosol of hippocampal neuron cells is studied in comparison to biodegradation. Implications of this work for neuroscience, bio-medicine and single cell studies are discussed.     

Biofunctionalization of polyelectrolyte microcapsules with biotinylated polyethylene glycol-grafted liposomes

Hollow polyelectrolyte microcapsules (PEMC) are prepared using layer-by-layer self-assembly of polyelectrolytes on melamine formaldehyde templates, followed by template dissolution, and subsequent coating with biotinylated polyethylene glycol-grafted liposomes. These potential site-specific carrier systems show a high specificity for NeutrAvidin binding and a strong resistance against unspecific protein binding. It is concluded that this design with NeutrAvidin as the outermost layer of such capsules provides an ideal platform for the biofunctionalization of PEMC as drug delivery systems or as artificial cell-like structures for biomimetic studies.     

药用微胶囊的制备

微胶囊技术是21世纪重点研究开发的高新技术之一,用途广泛。本文综述了微胶囊的制备原理及方法,着重阐述了采用超临界二氧化碳技术和溶剂蒸发法制备药物微胶囊的最新研究进展,介绍了超临界流体快速膨胀(RESS)法、超临界流体抗溶剂(SAS)法和气体饱和溶液微粒制备(PGSS)法的特点,总结了溶剂蒸发法制备微胶囊的原理和溶剂蒸发法制备药物微胶囊的工艺研究现状,分析了药物微胶囊的表征方法及性能,并对今后微胶囊技术的发展作了展望。     

Liquid crystal microcapsule medical device used for thermographic examination of the human female breast

A new medical device called Thermascan has been developed based on heat-sensitive microencapsulated liquid crystals. This thermographic device assists in early detection of breast abnormalities that are characterized by minor changes in tissue temperature and displayed by the color changes in the device. This liquid crystal device is used to screen patients who fall into the average to high risk category. The value of this diagnostic device is that it will detect minute temperature changes that occur in the breast from very small heat-producing cancers.     

Changes in charge density and softness of a poly(l-lactide) microcapsule surface in the hydrolytic degradation process

The changes in surface properties of poly(l-lactide) microcapsules caused by hydrolytic degradation have been studied with electrophoretic mobility measurements. An electrokinetic model has been applied to examine the electrophoretic mobility data, which were previously analyzed with a model that does not take into account the liquid flow inside the microcapsule membrane [K. Makino, H. Ohshima and T. Kondo, J. Microencapsulation, 4 (1987) 47]. The present new model involves two parameters, the charge density in the microcapsule membrane and a softness parameter, the latter of which characterizes the reciprocal of the frictional coefficient of the polymer exerted on the liquid flow. Information about the changes in charge density and in the softness of the poly(l-lactide) microcapsule surface have been newly obtained. The surface charge density increases by the cleavage of ester bonds in the polymer chain in the initial stage of the degradation process. It then gradually decreases down to the value for intact poly(l-lactide) microcapsules as a result of the release of degraded polymer segments from the microcapsule surface. Also, as the degradation proceeds, the softness parameter value increases, suggesting that the surface of the microcapsules becomes softer, probably because the surface becomes porous. The above change in the softness and the decrease in charge density at the later stage of the degradation both imply liberation of charged polymer segments. The degradation of poly(l-lactide) microcapsules proceeds by alternate repetition of cleavage of the ester bonds in the polymer chains and liberation of the degraded polymer segments from the surface.