Impact of particle size and surface modification on gold nanoparticle penetration into human placental microtissues.

AIM: Nanoparticle-based drug carriers hold great promise for the development of targeted therapies in pregnancy with reduced off-target effects. Here, we performed a mechanistic in vitro study on placental localization and penetration of gold nanoparticles (AuNPs) in dependence of particle size and surface modification. MATERIALS & METHODS: AuNP uptake and penetration in human placental coculture microtissues was assessed by inductively coupled plasma-mass spectrometry, transmission electron microscopy and laser ablation-inductively coupled plasma-mass spectrometry. RESULTS: Higher uptake and deeper penetration was observed for smaller (3-4 nm) or sodium carboxylate-modified AuNPs than for larger (13-14 nm) or PEGylate AuNPs, which barely passed the trophoblast barrier layer. CONCLUSION: It is possible to steer placental uptake and penetration of AuNPs by tailoring their properties, which is a prerequisite for the development of targeted therapies in pregnancy.

Tracking immune-related cell responses to drug delivery microparticles in 3D dense collagen matrix.

Beyond the therapeutic purpose, the impact of drug delivery microparticles on the local tissue and inflammatory responses remains to be further elucidated specifically for reactions mediated by the host immune cells. Such immediate and prolonged reactions may adversely influence the release efficacy and intended therapeutic pathway. The lack of suitable in vitro platforms limits our ability to gain insight into the nature of immune responses at a single cell level. In order to establish an in vitro 3D system mimicking the connective host tissue counterpart, we utilized reproducible, compressed, rat-tail collagen polymerized matrices. THP1 cells (human acute monocytic leukaemia cells) differentiated into macrophage-like cells were chosen as cell model and their functionality was retained in the dense rat-tail collagen matrix. Placebo microparticles were later combined in the immune cell seeded system during collagen polymerization and secreted pro-inflammatory factors: TNFα and IL-8 were used as immune response readout (ELISA). Our data showed an elevated TNFα and IL-8 secretion by macrophage THP1 cells indicating that Placebo microparticles trigger certain immune cell responses under 3D in vivo like conditions. Furthermore, we have shown that the system is sensitive to measure the differences in THP1 macrophage pro-inflammatory responses to Active Pharmaceutical Ingredient (API) microparticles with different API release kinetics. We have successfully developed a tissue-like, advanced, in vitro system enabling selective "readouts" of specific responses of immune-related cells. Such system may provide the basis of an advanced toolbox enabling systemic evaluation and prediction of in vivo microparticle reactions on human immune-related cells.

In vitro investigations of a novel wound dressing concept based on biodegradable polyurethane.

Non-healing and partially healing wounds are an important problem not only for the patient but also for the public health care system. Current treatment solutions are far from optimal regarding the chosen material properties as well as price and source. Biodegradable polyurethane (PUR) scaffolds have shown great promise for in vivo tissue engineering approaches, but accomplishment of the goal of scaffold degradation and new tissue formation developing in parallel has not been observed so far in skin wound repair. In this study, the mechanical properties and degradation behavior as well as the biocompatibility of a low-cost synthetic, pathogen-free, biocompatible and biodegradable extracellular matrix mimicking a PUR scaffold was evaluated in vitro. The novel PUR scaffolds were found to meet all the requirements for optimal scaffolds and wound dressings. These three-dimensional scaffolds are soft, highly porous, and form-stable and can be easily cut into any shape desired. All the material formulations investigated were found to be nontoxic. One formulation was able to be defined that supported both good fibroblast cell attachment and cell proliferation to colonize the scaffold. Tunable biodegradation velocity of the materials could be observed, and the results additionally indicated that calcium plays a crucial role in PUR degradation. Our results suggest that the PUR materials evaluated in this study are promising candidates for next-generation wound treatment systems and support the concept of using foam scaffolds for improved in vivo tissue engineering and regeneration.

In vitro mechanistic study towards a better understanding of ZnO nanoparticle toxicity.

ZnO nanoparticles (NPs) elicit significant adverse effects in various cell types, organisms and in the environment. The toxicity of nanoscale ZnO has often been ascribed to the release of zinc ions from the NPs but it is not yet understood to which extent these ions contribute to ZnO NP toxicity and what are the underlying mechanisms. Here, we take one step forward by demonstrating that ZnO-induced Jurkat cell death is largely an ionic effect involving the extracellular release of high amounts of Zn(II), their rapid uptake by the cells and the induction of a caspase-independent alternative apoptosis pathway that is independent of the formation of ROS. In addition, we identified novel coating strategies to reduce ZnO NP dissolution and subsequent adverse effects.

Antibacterial burst-release from minimal Ag-containing plasma polymer coatings.

Biomaterials releasing silver (Ag) are of interest because of their ability to inhibit pathogenic bacteria including antibiotic-resistant strains. In order to investigate the potential of nanometre-thick Ag polymer (Ag/amino-hydrocarbon) nanocomposite plasma coatings, we studied a comprehensive range of factors such as the plasma deposition process and Ag cation release as well as the antibacterial and cytocompatible properties. The nanocomposite coatings released most bound Ag within the first day of immersion in water yielding an antibacterial burst. The release kinetics correlated with the inhibitory effects on the pathogens Pseudomonas aeruginosa or Staphylococcus aureus and on animal cells that were in contact with these coatings. We identified a unique range of Ag content that provided an effective antibacterial peak release, followed by cytocompatible conditions soon thereafter. The control of the in situ growth conditions for Ag nanoparticles in the polymer matrix offers the possibility to produce customized coatings that initially release sufficient quantities of Ag ions to produce a strong adjacent antibacterial effect, and at the same time exhibit a rapidly decaying Ag content to provide surface cytocompatibility within hours/days. This approach seems to be favourable with respect to implant surfaces and possible Ag-resistance/tolerance built-up.