nanohealth

ANWENDUNGEN

Oral application


One aspect of the Nano-HEALTH project is the development and optimization of so-called thiomers nanoparticles which contain sulfur-hydrogen (thiol groups). Thanks to their chemical properties, the thiomers show promise in improving Mucoadhesion and permeation through the membrane as well as having an enzyme-inhibiting effect.
These innovative nanoparticles are to be taken orally and work as a transport medium to e.g. administer insulin purposefully and rapidly to the small intestine mucosa. There, it is absorbed through the small intestine into the bloodstream. This technique could be used to cover the basal insulin needs of diabetics.
With the help of thiomers nanoparticles, a new efficient, and, especially non-invasive, oral transport system for insulin and calcitonin is being designed.

  

Depot formulation

It will be developed a novel localised therapy for ischaemic tissue associated with diabetes and other disorders involving the local injection of thiomeric NPs containing an angiogenic peptide able to provide localised long term release of the peptide through a depot effect.  Formulation of the peptide in this manner will enable facile administration by standard needle injection and also improve the local biodistribution by promoting the distribution in the target muscle tissue through enhanced diffusion. As well as exploring NP formulation, modification of the peptide will be explored as a way of enhancing this effect (for instance through increased peptide stability).
Development of a new NP-based depot formulation for the local delivery of the neuropeptide to improve tissue perfusion in ischemic limbs, for instance of diabetic patients.

Stem cells

The goal is the development of nanotechnology methods for labeling stem cells to make them visible through magnetic resonance analysis in a tolerable non-invasive procedure. The latest methods, which have already been implemented, serve as a basis for the production of human adult stem cells in sufficient quantity and clinical quality.
In the starting phase of the project, stem cells were loaded with commercially available superparamagnetic nanoparticles. Then, stem cells are loaded with newly developed Nano-Health nanoparticles for high-resolution magnetic resonance. Equipped with this basic knowledge, in an innovative Bioequivalent, which, due to it standardization, replaces numerous animal experiments, defined amounts of labeled stem cells are analyzed and gradually marked for their traceability in a high-resolution 3 Tesla magnetic resonance system. In comparison to animal experiments, the standardization and stability of Bioequivalents aims to allow faster optimization of the process of stem cell markers and of  imaging parameters. With this work, significant new insights into the behavior of stem cells in three-dimensional space combined with a temporal analysis (fourth dimension) are expected.
This strategy forms the basis for the targeted development of new imaging techniques that will help to improve assessability and development of new stem cell therapies.

  

Analytics

Here one deals with the development of new miniaturized separation materials for modern liquid chromatography in coupling with mass spectrometry (HPLC-MS) using the Ring-Opening Metathesis Polymerization. The HPLC-MS is one of the most important analytical methods, especially in peptide and protein quantification. In this project, nano-monoliths have been developed which, due to their nanostructuring, revealed themselves to have very advantageous seperation properties in the field of nanoparticle analysis in terms of active ingredient release. These monoliths were thoroughly characterized by chromatography and subsequently surface functionalized.
These monoliths were used to determine the Pharmacokinetic of drug loaded nanoparticles and have clear advantages when compared with packed columns. Through their unique structure, nanoparticle suspensions without prior separation of the nanoparticles are injected onto the monolith. This time-consuming ultracentrifugation accounts for the separation of the nanoparticles which requires at least two hours. Thus, the investigation of Pharmacokinetic from 0-2 hours is possible. 

Peptid-Target Design

Effective targeting molecules are key components of targeted nanomedicines. New concepts for the development of optimised targeting molecules will be assessed. In vitro assays and specific tissues and cell lines expressing the targeted molecules will be required for this.
Based on the promising results obtained to date in the development of new and innovative NPs mainly for molecular imaging purposes, there is a good rationale for focusing more on the development of suitable targeting molecules. Three targets will be addressed:

(i) vulnerable atherosclerotic plaque by detecting neovascularisation by MRI and in oncology on
(ii) highly over expressed G-coupled receptors on tumours and on

(iii) the neovascularisation of these tumours for radio-diagnosis by SPECT, PET and also for radiotherapy using targeted NPs.
For neo-angiogenesis, we will focus on synthetic analogue. To discover and optimise targeting molecules, an approach based on a combination of molecular modelling (similarity design) and randomized production and screening techniques (Phage-Display, synthetic peptide-libraries) will be used. Selected targets will be first validated using biosamples provided by the Bio bank of the Med. Univ. of Graz. To maximize the chance of generating useful results within this short project period, a maximum of 2 targets will be selected in close collaboration and consultation with the participating industrial partners to achieve utilizable results.
This project will result in an optimized approach for the development of new targeting sequences for known targets. 

Arteriosclerosis 

With the aid of nanotechnology, Nano-Health is working on a new method for the early diagnosis and treatment of atherosclerosis. Therefore, multifunctional nanoparticles were conjugated with monoclonal antibodies and / or biomarkers. These functionalized nanoparticles are designed to bind to structures that are specific to the atherosclerotic plaque in the early stages. The use of these nanoparticles allows for diagnostic imaging. For detection, a high-energy 3 Tesla MRI scanner is used. Furthermore, NP complexes, in addition to selective diagnostic imaging, are analyzed for their potential as a carrier for highly effective therapeutic agents (e.g. inflammation-inhibiting Biologica).

 

The term “Nanotoxicology” was introduced in 2004 by Donaldson and colleagues who realized that nano-scale particles behave very differently from their larger counterparts. The effects of the exposure and the mechanism of toxicity are much better documented for environmental combustion-derived NPs than for NPs designed for medical use.

Within Nano-Health safety and toxicology will be addressed using a panel of in-vitro screening assays to prevent further development of toxic nanoparticles. Diverse aspects of toxicity including cytotoxicity, hemocompatibility and genotoxicity will be addressed. NPs with no obvious toxicity in the dose range of interest will be screened for in-vivo toxicity in rats and mice. For these applications standardised protocols will be used and adapted to the application of NPs. Tests investigating organ specific toxicity will be added if indicated by blood analysis or histopathological evaluation of in-vivo experiments. The effect on the immune system is studied in more detail to characterise the allergenic potential of NPs. As particles after a single exposure may be retained in the body for a prolonged time a new testing system will be developed addressing chronic cytotoxicity. The relationship between in vitro and in vivo toxicity will be explored for selected particles.

One of the results will be a standardized toolbox of in-vitro assays to address acute and chronic toxicity of nanoparticles.