Pulmonary drug delivery with aerosolizable nanoparticles in an ex vivo lung model

The use of colloidal carrier systems for pulmonary drug delivery is an emerging field of interest in nanomedicine. The objective of this study was to compare the pulmonary absorption and distribution characteristics of the hydrophilic model drug 5(6)-carboxyfluorescein (CF) after aerosolization as solution or entrapped into nanoparticles in an isolated rabbit lung model (IPL). CF-nanoparticles were prepared from a new class of biocompatible, fast degrading, branched polyesters by a modified solvent displacement method. Physicochemical properties, morphology, encapsulation efficiency, in vitro drug release, stability of nanoparticles to nebulization, aerosol characteristics as well as pulmonary dye absorption and distribution profiles after nebulization in an IPL were investigated. CF-nanoparticles were spherical in shape with a mean particle size of 195.3+/-7.1nm, a polydispersity index of 0.225+/-0.017 and a zeta-potential of -28.3+/-0.3mV. Encapsulation efficiencies of CF were as high as about 60% (drug loading of 3% (w/w)); 90% of the entrapped CF were released during the first 50min in vitro. Nanoparticle characteristics were not significantly affected by the aerosolization process utilizing a vibrating mesh nebulizer. After deposition of equal amounts of CF in the IPL, less CF was detected in the perfusate for CF-nanoparticles (plateau concentration 9.2+/-2.4ng/ml) when compared to CF aerosolized from solution (17.7+/-0.8ng/ml). In conclusion, the data suggest that inhalative delivery of biodegradable nanoparticles may be a viable approach for pulmonary drug delivery. Moreover, a targeting effect to the lung tissue is claimed.     

Self-assembled biodegradable amphiphilic PEG-PCL-lPEI triblock copolymers at the borderline between micelles and nanoparticles designed for drug and gene delivery

Amphiphilic PEG-PCL-PEI triblock copolymers self-assemble into nano-scaled, positively charged, multifunctional carriers, suitable for drug and gene delivery. A set of block copolymers with varying hydrophilic/hydrophobic ratio (systematically altered at the borderline of micelle and particle forming polymers) was synthesized, characterized and assembled into carriers. A detailed structural characterization in the liquid state of these assemblies was carried out: carrier size was determined using dynamic light scattering, cryogenic scanning electron microscopy and atomic force microscopy. Nuclear magnetic resonance analyses elucidated carrier's core-shell structure. ζ-potential and thickness of the hydrophilic outer polymer shell were determined by laser Doppler anemometry. Subsequently the impact of carrier's structure on its features (stability and toxicity) was investigated. Polymers hydrophilic in nature formed small (<40?nm) micelle-like carriers, whilst hydrophobic polymers aggregated to larger particle-like assemblies (>100?nm). Monitoring carrier size as a function of initial polymer concentration clarified different assembly mechanisms. Shell thickness, colloidal stability and toxicity were found to depend on the length of the hydrophilic polymer block. Due to controllable size, charge, stability and toxicity, this class of novel carriers is a promising candidate for prospective co-delivery of drugs and nucleic acids.     

Consensus treatment recommendations for late-onset Pompe disease

Introduction: Pompe disease is a rare, autosomal recessive disorder caused by deficiency of the glycogen‐degrading lysosomal enzyme acid alpha‐glucosidase. Late‐onset Pompe disease is a multisystem condition, with a heterogeneous clinical presentation that mimics other neuromuscular disorders. Methods: Objective is to propose consensus‐based treatment and management recommendations for late‐onset Pompe disease. Methods: A systematic review of the literature by a panel of specialists with expertise in Pompe disease was undertaken. Conclusions: A multidisciplinary team should be involved to properly treat the pulmonary, neuromuscular, orthopedic, and gastrointestinal elements of late‐onset Pompe disease. Presymptomatic patients with subtle objective signs of Pompe disease (and patients symptomatic at diagnosis) should begin treatment with enzyme replacement therapy (ERT) immediately; presymptomatic patients without symptoms or signs should be observed without use of ERT. After 1 year of ERT, patients' condition should be reevaluated to determine whether ERT should be continued. Muscle Nerve, 2012     

小腿带腓肠神经远端筋膜蒂皮瓣移植的应用进展

目的:综合分析小腿、踝、足部复合伤后组织缺损与筋膜皮瓣移植的修复关系以及小腿带腓肠神经远端筋膜蒂皮瓣移植的解剖学基础与临床应用进展。资料来源:应用计算机检索Medline1990-01/2006-10有关小腿带腓肠神经远端筋膜蒂皮瓣移植的文章,检索词“sural nerve,fascia,flap,leg,lesser saphena”,并限定文章语言种类为English。同时计算机检索CNKI数据库1996-01/2006-10有关小腿带腓肠神经远端筋膜蒂皮瓣移植的文章,检索词“腓肠神经,皮瓣,筋膜,小隐静脉”,并对检索词进行分别组合,限定文章语言种类为中文。资料选择:对检索到的小腿带腓肠神经远端筋膜蒂皮瓣移植方面的相关信息进行整理,阅读2005,2006年度专业核心期刊的相关文章,在CNKI阅读查询到的引用2次以上的文献,选取针对性强的文章。资料提炼:有关小腿带腓肠神经远端筋膜蒂皮瓣移植的文献,有解剖学研究、病例报道、解剖与临床结合论著及综述等,相似的同一研究较多,国内研究、运用较国外丰富,其中有30篇纳入研究范畴。资料综合:小腿带腓肠神经远端蒂筋膜皮瓣具有以下优点:①蒂部具有穿支动脉,同时携带位于深筋膜层的皮神经及浅静脉,皮瓣移植难度较小,修复创面满意,不损失肢体的知名主干血管。②蒂部成形灵活,属于生理性皮瓣,成活可靠。③可重建感觉,以同样血供为基础的可形成复合瓣。小腿带腓肠神经远端筋膜蒂皮瓣是解决膝以下,足跖骨头以上皮肤组织缺损的简单、安全、效果良好的方法。结论:小腿带腓肠神经远端筋膜蒂皮瓣移植已成为创伤修复日渐青睐的手术方式,但在适应症、皮瓣血运基础、对小隐静脉处理、皮瓣质量(大小、外观、感觉)、术后护理等方面有待达成共识,使之成为修复创面的常用手段。     

The formation and function of the neutrophil phagosome

Neutrophils are the most abundant circulating leukocyte and are crucial to the initial innate immune response to infection. One of their key pathogen-eliminating mechanisms is phagocytosis, the process of particle engulfment into a vacuole-like structure called the phagosome. The antimicrobial activity of the phagocytic process results from a collaboration of multiple systems and mechanisms within this organelle, where a complex interplay of ion fluxes, pH, reactive oxygen species, and antimicrobial proteins creates a dynamic antimicrobial environment. This complexity, combined with the difficulties of studying neutrophils ex vivo, has led to gaps in our knowledge of how the neutrophil phagosome optimizes pathogen killing. In particular, controversy has arisen regarding the relative contribution and integration of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived antimicrobial agents and granule-delivered antimicrobial proteins. Clinical syndromes arising from dysfunction in these systems in humans allow useful insight into these mechanisms, but their redundancy and synergy add to the complexity. In this article, we review the current knowledge regarding the formation and function of the neutrophil phagosome, examine new insights into the phagosomal environment that have been permitted by technological advances in recent years, and discuss aspects of the phagocytic process that are still under debate.