Completed PhD and PostDoc projects since 2021


Below you can read more about the compleeted PhD and PostDoc projects in our research group

PhD student:
Lisa  Myrseth Hemmingsen

Main supervisor:
Natasa Skalko-Basnet

Lipid and polymer based drug delivery systems for membrane active peptides (2022)

In a global perspective, it is estimated that 1-2 % of the population will experience at least one chronic wound throughout their lifetime. With an aging population with increasingly more underlying diseases, the situation might worsen in the coming years. Bacterial biofilms in these wounds are among the major contributors to the challenges in wound management and antimicrobial resistance. Biofilms are found in up to 80 % of all chronic wounds and the bacteria embedded in the extracellular polymeric substance often require a 1000-fold increase of the antibiotic dose. We need novel strategies to overcome these challenges and we propose pharmaceutical technology as a possible solution. 
In this project, we work with novel, patented membrane-active antimicrobials synthesised at our university. The aim is to develop lipid and polymer-based drug delivery systems for localized treatment of chronic wounds, especially biofilm-infected wounds, using these novel antimicrobials. Optimization of these topical formulations is expected to improve the therapeutic action of membrane-active antimicrobials to reduce cytotoxicity and improve the antimicrobial activity. 

PostDoc: Sybil Obuobi

Supervisor:
Natasa Skalko-Basnet

SMART THERAPEUTIC HYBRID MATERIALS AS ADJUVANTS FOR NANOMEDICINE (2022)

Inspired by the spatiotemporal accuracy of elevated biochemical signals within the tissue microenvironment and their impact on controlling disease pathogenesis, smart functional biomaterials that adapt their properties to these cues have provided new opportunities in developing targeted nanomedicines. Notable progress in the fabrication of these materials has shown precedence in controlling drug delivery and minimizing toxicity. Nevertheless, the complexity of many disease conditions and emergence of drug resistance preclude drug monotherapy. Within this context, smart hybrid nanocarriers fabricated with biomolecules such as nucleic acids, polysaccharides, proteins and lipids can revolutionized disease management by assuring multi-responsiveness and synergize functionality. Our work focuses on developing smart hybrid carrier systems that can deliver high doses of therapeutic cargoes, leverage the endogenous cues for site-specific drug release and limit toxicity. To achieve this, therapeutic cargoes (e.g., peptides) have been loaded into nucleic acid-based hybrid systems that combine nanostructured DNA and liposomes. We have demonstrated that this platform can address the current gap in liposomal formulations (i.e. poor loading efficiency). We have also achieved synergistic anti-inflammatory activity and successfully treated persistent intracellular infections using our hybrids. Future exploring seeks to adapt these systems in the diagnosis (e.g. infectious and metabolic diseases) and treatment of diseases (e.g. infectious, cardiovascular, gastrointestinal and central nervous system diseases). 

FUNDING
This project has received funding from the European Union’s Horizon 2020 Research & Innovation programme under grant agreement No. 834811.

RELEVANT PUBLICATIONS
1. Obuobi, S.*, Julin, K., Fredheim, E. G. A., Johannessen, M., Škalko-Basnet, N. (2020). Liposomal delivery of antibiotic loaded nucleic acid nanogels with enhanced drug loading and synergistic anti- inflammmatory activity against S. aureus intracellular infections. JOURNAL OF CONTROLLED RELEASE, 324, 620-632. doi:10.1016/j.jconrel.2020.06.002

2. Obuobi, S*., Škalko-Basnet, N. (2020). Nucleic acid hybrids as advanced antibacterial nanocarriers. PHARMACEUTICS, 12, 7, 643. doi:10.3390/pharmaceutics12070643
PhD student: 

Jennifer Cauzzo

 

Main supervisor:
Natasa Skalko-Basnet

Visualizing cellular internalization of lipid-based nanocarriers (2022)

The project aims to investigate the internalization of drug delivery systems (DDSs) within cells, with a focus on the challenges of labeling nanoparticles for imaging purposes. Lipid-based DDSs – such as liposomes and solid lipid nanoparticles, are utilized as model nanocarriers for their high biosafety, therapeutic relevance and structural versatility. The body clearance system is of particular interest for the project. Hence, the cellular testing is focused on macrophages and liver scavenging mechanisms, which are responsible for the recognition, internalization and dispatch of drugs and DDSs in the blood stream. The project involves different carrier preparation methods, such as thin film hydration, ethanol injection and microfluidics (in collaboration with Elvesys – Microfluidics Innovation Center, Paris, France), but also novel characterization techniques both label-dependent (i.e. fluorescence fluctuation super resolution microscopy) and label-free (i.e. quantitative phase microscopy). The cell internalization of nanocarriers is then followed, quantified and visualized with live cell imaging in light microscopy, flow cytometry, electron microscopy and through the combination of such techniques (in collaboration with Bayer AG – Applied Physics, Leverkusen, Germany). This project is part of an International Training Network funded by the European Union’s Horizon 2020 research and innovation programme, under the Marie Skłodowska-Curie grant agreement No. 766181.

DeLIVER-ITN website: https://www.deliver-itn.eu/index.php/en/

PhD student: 

Margherita Falavigna 

 

Main supervisor:
Gøril Eide Flaten

The development journey of an artificial intestinal model predicting oral drug absorption: the mucus-PVPA model (2021)

The development of one new drug can take up to 15 years and cost over 22 billion NOK. To overcome these time- and cost-related issues, the need for artificial tools mimicking the human body to study drug absorption has become ever so evident. For orally administered drugs, their capacity to reach the systemic blood circulation depends on their ability to dissolve in the gastrointestinal fluids and cross the intestinal membrane. To estimate how a drug would behave in patients, this project focuses on the development of the mucus-PVPA model, an artificial tool simulating the membrane and fluids in the intestine. The model is used to study drug permeation, and the obtained results are compared to animal studies. The comparison demonstrates that the artificial model is able to correctly predict drug absorption in animals, likely correlated to the one found in humans. Thus, this novel artificial model shows great potential for use as a tool in the development of new drugs and formulations.