Time frame: 2021-2024, No LIDER/56/0231/L-11/19/NCBR/2020; budget: 1,5 mln PLN principal investigator: Paulina Skupin-Mrugalska, PhD with habilitation
The aim of the project is to formulate BCS class II drugs in amorphous solid dispersions composed of polymer-phospholipid matrix and develop manufacturing technology by hot-melt extrusion (HME), which is a prominent candidate-enabling formulation strategy for oral drug administration and bioavailability enhancement.
The project will provide a comprehensive solution for the rapid prototyping of advanced pharmaceutical formulations and the design of the HME process. The solution provided should meet the requirements of pharmaceutical CROs and R&D departments in Poland.
The project is multifaceted and multidisciplinary, aiming to develop a new class of pesticides for combating fungal and bacterial plant diseases. The innovation of the project lies in the use of photodynamic therapy technology, which represents a groundbreaking approach in plant protection. So far, there have been no light-activated plant protection agents on the market, making this project potentially pioneering in agriculture. This strategy aligns with the development of modern, ecological, and sustainable agriculture, offering an alternative to traditional, often toxic plant protection methods.
The project plans to develop six active chemical compounds, which will undergo detailed testing for biological efficacy on six different plant species. The research will include evaluating the effectiveness against pathogens as well as the impact on plant health and growth. The results will allow for the optimization of selected substances and their preparation for further development stages, including potential commercialization. The project represents a unique combination of innovative technologies and a sustainable approach, addressing the growing needs of contemporary agriculture for ecological and effective plant protection solutions.
Duration: 09.2023 - 03.2025
Project leader: Dr. Daniel Ziental
The project aims to address the growing issue of antibiotic resistance by developing new treatment methods for infections caused by antibiotic-resistant microorganisms. The research focuses on innovative photodynamic therapy (PACT) and sonodynamic antimicrobial therapy (SACT), which could serve as alternatives to traditional antibiotics. The main objective is to assess the potential of two compounds – violacein and deoxyviolacein – as photo- and sonosensitizers. These indole-based dyes, derived from Chromobacterium violaceum, exhibit antimicrobial activity and can generate reactive oxygen species under light or ultrasound exposure, leading to the death of microorganisms. So far, violacein has primarily been studied in the context of cancer therapies, but its potential for treating bacterial infections has not been fully explored.
The project aims to develop new formulations of these compounds that address their water insolubility, thus expanding their therapeutic application. The researcher plans to use liposomes to create stable and effective preparations, which could facilitate the development of new sensitizers for dynamic therapies. The formulations will also be tested on selected cancer cell lines to evaluate their potential for treating cancer using SACT. Additionally, toxicity will be assessed on fibroblasts to gain a thorough understanding of the safety of these compounds in therapy.
The results of this project could mark a breakthrough in the treatment of antibiotic-resistant infections, offering new tools in the fight against bacteria resistant to traditional drugs.
Time frame: 2022-2025, No 2021/41/N/NZ7/04105; budget: 210 000 PLN
principal investigator: Mikołaj Czajkowski, MPharm
The project's main goal is to design novel Dual-Loaded Lipid Nanoparticles (DL-LNPs), a delivery carrier containing gefitinib, a first-generation EGFR-TKI and small interfering RNA (siRNA).
In our project, the siRNA will be used to inhibit the expression of a certain gene, responsible for the development of acquired resistance in NSCLC cells to EGFR-TKIs therapy. The advantage of the project is that, instead of administering the two therapeutics - gefitinib and siRNA - separately, we will develop one carrier system co-delivering both molecules.
The proposed strategy may open new doors in the field of drugs and genes delivery in combating drug resistance.
The presented project contributes to the development of RNA-based therapeutics and vaccines in Poland and worldwide. This is of great importance for a currently developed national strategy to implement RNA-based technology, where the advanced delivery systems are absolutely essential for therapeutic material protection and efficacious delivery, so crucial for proper therapeutic performance.
Above all, the presented project results may have great potential to significantly impact the field of drug delivery and improve the efficiency of therapy of lung and other types of cancer.
Time frame: 2022-2027, No 2021/42/E/NZ7/00287; budget: 4 284 986 PLN
Principal investigator: Paulina Skupin-Mrugalska, PhD with habilitation
Our research aims to adapt the AF4 method to isolate lipid nanoparticle-corona complexes from unbound proteins after incubation in various biological fluids.
Then, to better understand the role of the protein corona, we will examine the influence of the corona on the interaction of liposomes and lipid nanoparticles with selected cells (macrophages, epithelial cells and cancer cells), which are potential "recipients" of nanoparticles used in medicine and their cargos, i.e. drug molecules or a nucleic acid (e.g., mRNA). In the final stage, we will examine the corona's influence on nucleic acid delivery (model mRNA) efficiency in lipid nanoparticles (analogous to those used in mRNA vaccines against the SARS-Cov-2 virus) in cell culture and in an animal model.
Why are the results of our project important? The outcomes of our project will enhance understanding of (i) the composition of protein corona formed in different fluids on the surface of the most commonly used types of drug delivery system (liposomes, lipid nanoparticles) and (ii) nanoparticle-corona complexes uptake mechanism in cells that are physiological targets for those nanoparticles. Thus, we could further design lipid nanoparticles and liposomes with better properties and improved efficacy. Importantly, the presented project contributes to understanding the corona effect on mRNA delivery by lipid nanoparticles. The above aspect is important while facing the increasing role of mRNA therapeutics and delivery systems. In addition, project results could initiate further research that will increase the effectiveness of drugs that use nanoparticles as drug carriers and allow the use of the properties of the protein corona in new applications, e.g., as markers, diagnostics and other purposes.
SONATA (completed):
Time frame: 2017-2023, No 2016/21/D/NZ7/01607; budget: 847 150 PLN
Principal investigator: Paulina Skupin-Mrugalska, PhD with habilitation
PRELUDIUM:
Time frame: 2013-2016, No 2012/07/N/NZ7/04325; budget: 150 000 PLN
Principal investigator: Łukasz Sobotta, PhD
In the project PRELUDIUM and SONATA, we designed theranostic liposomes carrying contrast agent (CA) for magnetic resonance imaging and a photosensitizer (ZnPc) for photodynamic therapy of cancer, resulting in a formula with desirable properties for diagnosis and treatment of head and neck cancer. The research resulted in novel methods suited for preparing and characterizing theranostic liposomes (ThLip) and contributed to understanding the ThLip structure-properties relationship. Importantly, theranostic liposomes were characterized by relaxivities higher than those of commercially used CA, e.g., Magnevist®. The above finding triggered further studies and has raised the possibility of reducing the amount of gadolinium, which can greatly reduce the risk of nephrotoxicity.
More information can be found here:
Skupin-Mrugalska, P.; Zalewski, T.; Elvang, P. A.; Nowaczyk, G.; Czajkowski, M.; Piotrowska-Kempisty, H. Insight into Theranostic Nanovesicles Prepared by Thin Lipid Hydration and Microfluidic Method. Colloids and Surfaces B: Biointerfaces 2021, 205, 111871. https://doi.org/10.1016/j.colsurfb.2021.111871.
Skupin-Mrugalska, P.; Elvang, P. A.; Brandl, M. Application of Asymmetrical Flow Field-Flow Fractionation (AF4) for Characterizing the Size and Drug Release Kinetics of Theranostic Lipid Nanovesicles. International Journal of Molecular Sciences 2021, 22 (19), 10456. https://doi.org/10.3390/ijms221910456.
Skupin-Mrugalska, P.; Sobotta, L.; Warowicka, A.; Wereszczynska, B.; Zalewski, T.; Gierlich, P.; Jarek, M.; Nowaczyk, G.; Kempka, M.; Gapinski, J.; Jurga, S.; Mielcarek, J. Theranostic Liposomes as a Bimodal Carrier for Magnetic Resonance Imaging Contrast Agent and Photosensitizer. Journal of Inorganic Biochemistry 2018, 180, 1–14. https://doi.org/10.1016/j.jinorgbio.2017.11.025.
Completed.
Time frame: 2017-2023, No 2016/23/D/NZ7/03954; budget: 990 889 PLN
Principal investigator: Hanna Piotrowska-Kempisty, PhD with habilitation
PHOSPHOLIPID RESEARCH CENTER, HEIDELBERG, Germany
Principal investigator: Paulina Skupin-Mrugalska, PhD with habilitation
Time frame: 2021-2024, No PSM-2020-085/1budget: 120 560 EUR
Professor Dr. Martin Brandl (collaborator) – Drug Transport and Delivery Group, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense DK-5230, Denmark (mmb@sdu.dk)
Dr. Edyta Szalek, Dr. Agnieszka Karbownik (collaborator) – Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences
Kinga Biedrzycka, M.Sc.Eng. (collaborator) – Applied Manufacturing Science (kinga.biedrzycka@ams-pharma.org)
The project aims to use phospholipids as components of mixed phospholipid and polymer-based amorphous solid dispersions for oral delivery of poorly soluble drugs. Selected formulations will be screened using cellulose or polyvinylpyrrolidone derivatives and (hydrogenated) phospholipids. Initially, Fenofibrate (FEN), an orally active lipid-regulating drug, will be used as a model drug in the project. FEN is a Biopharmaceutical Classification System (BCS) class II drug in which its oral bioavailability is limited by poor aqueous solubility. Amorphous solid dispersions of drug substances in a polymer-phospholipid matrix will be prepared by simple film-casting/batch-melting and later by hot-melt extrusion. FEN is commonly used as a model drug for amorphous solid dispersion studies and has been reported as a suitable candidate for hot-melt extrusion manufacturing. The effect of phospholipid on the formation of amorphous solid dispersion of FEN will be evaluated by screening techniques, including analysis of dispersed mixed films.
Further, the pharmaceutical performance of formulations will be studied by dissolution testing in biorelevant media. Special efforts will be focused on establishing a hot-melt extrusion process for preparing FEN amorphous solid dispersion in a polymer/phospholipid matrix. Finally, the bioavailability of a drug in selected formulations with and without phospholipids will be compared with an originator in vivo.
The project's innovative aspect embraces carriers for oral application based on mixed matrices composed of polymers and (hydrogenated) phospholipids, in which the drug is present in an amorphous state. These carriers can increase the bioavailability of the incorporated drug and have not been screened and characterized in detail so far. Therefore, it is assumed that the research project outcome will increase the interest in applying hydrogenated phospholipids as an excipient for oral formulations.
