We synthesised silica nanoparticles (SiNP) with covalently linked cationic surface modifications and demonstrated their ability to electrostatically bind, condense and protect plasmid DNA. These particles might be utilised as DNA carriers for gene delivery. All nanoparticles were sized between 10 and 100 nm and displayed surface charge potentials from +7 to +31 mV at pH 7.4. They were produced by modification of commercially available (IPAST) or in-house synthesised silica particles with either N-(2-aminoethyl)-3-aminopropyltrimethoxysilane or N-(6-aminohexyl)-3-aminopropyltrimethoxysilane. All particles formed complexes with pCMVbeta plasmid DNA as evidenced by ratio dependent retardation of DNA in the agarose gel and co-sedimentation of soluble DNA with nanoparticles. High salt and alkaline pH did inhibit complex formation. Absorption onto the particles also decreased the hydrodynamic dimensions of plasmid DNA as shown by photon correlation spectroscopy. Complexes formed in water at a w/w ratio of Si26H:DNA (pCMVbeta) of 300 were smallest with a mean hydrodynamic diameter of 83 nm. For effective condensation a w/w ratio of Si26H:DNA of 30 was sufficient. Further, the absorbed DNA was protected from enzymatic degradation by DNase I.

SummaryModels of the outer epithelia of the human body -namely the skin, the intestine and the lung -have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report.

The respiratory tract holds promise as an alternative site of drug delivery due to fast absorption and rapid onset of drug action, with avoidance of hepatic and intestinal first-pass metabolism as an additional benefit compared to oral drug delivery. At present, the pharmaceutical industry increasingly relies on appropriate in vitro models for the faster evaluation of drug absorption and metabolism as an alternative to animal testing. This article reviews the various existing cell culture systems that may be applied as in vitro models of the human air-blood barrier, for instance, in order to enable the screening of large numbers of new drug candidates at low cost with high reliability and within a short time span. Apart from such screening, cell culture-based in vitro systems may also contribute to improve our understanding of the mechanisms of drug transport across such epithelial tissues, and the mechanisms of action how advanced drug carriers, such as nanoparticles or liposomes, can help to overcome these barriers. After all, the increasing use and acceptance of such in vitro models may lead to a significant acceleration of the drug development process by facilitating the progress into clinical studies and product registration.

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