Research topics

We use innovative formulations and manufacturing technologies for creating drug delivery systems corresponding to the needs of modern society. Our research focuses mainly on electrospinning and micro-extrusion-based or fused deposition modelling 3D printing methods. These methods provide a tool for designing intricate polymeric structures with the benefit of mimicking tissue extracellular matrix and/or allowing fine-tuned spatiotemporal control over drug release. Additionally, 3D-printing offers a highly flexible platform to produce personalized medicines with easily adjustable doses and selection of APIs. We have also experience in developing liposomal and other nanocarrier based DDSs (such as polymersomes, solid lipid nanoparticles), providing a versatile platform to enhance the permeability and stability of drugs.

Comprehensive understanding of the material and process characteristics is crucial for the implementation of novel technologies. Thus, our research aims to improve the understanding of these factors starting from the molecular level and solid-state properties of the materials, influence of process parameters, and coming to see how these define the structural properties of produced materials and how it all affects biopharmaceutical properties that finally translate into biological responses.

Chronic wounds and wound infections are a major problem for society and patients. As current therapeutic options lack efficacy, especially in the presence of biofilm, new solutions are needed. Importantly, it is recognized that antimicrobial strategies play an integral part in the management of non-healing wounds. Our aim is to design and develop novel clinically relevant antimicrobial wound matrices, that would exhibit both desirable structural properties (oxygen permeability, high effective surface area and porosity promoting hemostasis and absorption of wound exudate) and have the capability to deliver drugs to the site of action at a controlled rate.  In addition to the antimicrobial drugs, we have taken the next step to incorporate living bacterial cells capable of producing antimicrobial substances into the electrospun nanofibers. Such electrospun wound matrices can be tuned to be sensitive and responsive to the environmental changes in the wound.

Oral cavity represents a challenging setting for wound healing due to bacteria-laden environment and constant physical trauma. Localized antimicrobial treatment of oral wounds and infections, e.g., periodontitis, offer several advantages over systemic administration, such as allowing higher antibiotic levels while avoiding systemic toxicity, prolonged retention of antibiotic at the target site with the consequent decreased possibility of emergence of bacterial resistance, and enhanced patient compliance. Recognizing these advantages, we develop electrospun antimicrobial DDSs for the local treatment of oral wounds and infections.

DOI: 10.1016/j.ejps.2018.07.024

We see that electrospun wound matrices are unique drug delivery systems that need special analytical techniques in addition to the established methods for the evaluation of their performance. Thus, in parallel with the development of wound matrices we also develop methods and biorelevant models which enable to understand their behavior in biological environment, safety and efficacy, unraveling the structure and activity relationships, and more importantly help us to understand the wound matrix-bacteria-eukaryotic cell interactions in wound environment. Better understanding of these relationships helps to guide rational design of safe and effective electrospun fibrous wound dressings.

For example, conventional drug release testing methods do not reflect the wound environment adequately and cause difficulties for correlating and predicting biological activity from the dissolution data. We have developed biorelevant hydrogel-based drug release and diffusion assays using extraction/HPLC, UV-imaging and bacterial bioreporters for detection. The latter provides an additional benefit of simultaneously monitoring antibacterial activity of the released drug. Also,  we put special emphasis on designing wound infection models with sessile bacteria in biofilm as it is recognized as a major culprit in therapeutic failure of non-healing wounds.

Many active pharmaceutical ingredients (APIs) may exist in different solid state forms. These forms may have different physicochemical properties, hence the solid state transformations during processing and storage may cause therapeutic, pharmaceutical as well as juridical problems. The main goal is to obtain an overall understanding about the solid state properties of APIs/excipients and their transformations. The main focus is to find novel approaches to modify the solid state properties of APIs which help to design the drug products with desired biopharmaceutical properties. Novel analysis methods are developed in parallel for solid state monitoring (spectroscopy with multivariate modelling).

Poor aqueous solubility is a major problem for drug development, therefore novel pharmaceutical technology approaches are sought to improve this. Preparation of amorphous solid dispersions (ASDs) is one of the possible solutions for this problem as amorphous drugs have improved apparent aqueous solubility and higher dissolution rate. The main scientific scope of the research work is to gain understanding of the solid-state transformation phenomena when preparing ASDs of poorly water-soluble drugs, and to exploit this knowledge in the development of stable formulations consisting of amorphous drug. Within ASDs the drug is stabilized in its amorphous form within a polymer matrix. Different processing and formulation-based methods, such as electrospinning (ES), milling at variable temperatures, quench cooling of co-melts and solvent evaporation, are used to prepare ASDs of poorly water-soluble APIs. Improved stability and dissolution behavior of ASDs together with better in vivo biopharmaceutical performance in rats has been demonstrated. Deeper investigation is performed to understand the miscibility of the ASDs and two-phase ASD systems. API-polymer interactions at the molecular level are investigated which significantly influence the stability of ASDs. Excipients are a relevant part of the pharmaceutical formulation and all excipients used in a dosage form preparation need to have a specified functionality. Novel substances are tested to be used as potential new pharmaceutical excipients (e.g. lignin, lignocellulose). Drug-excipient interactions during in vitro dissolution testing as well as in vivo animal studies have been investigated.

https://doi.org/10.1016/j.ejps.2018.06.004