METADRUG · Drug release metadynamics simulations with natural micro- and nanostructured excipients
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-01-01 → 2022-12-31
- EU contribution
- €171,473
- Participants
- 1
- Scheme
- MSCA-IF
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Results in brief
Drug release metadynamics simulations with natural micro- and nanostructured excipients
Development of new drug delivery systems for drugs as relevant as praziquantel (for schistosomiasis disease), without increasing the final cost of the treatment, are current challenges of the pharmaceutical industry to contribute to global health. The use of efficient and novel methodologies or techniques based on computational chemistry able to predict the release kinetics of the drugs in low-cost natural inorganic carriers, like clay minerals, could be of great help to improve the biopharmaceutical profile of the drugs. This would mean a huge saving in the costs of the investigation, allowing a fast screening of the performance of a great number of drug-clay systems and reducing the time with respect to in vitro experimental tests. Therefore, our goal in this project was to apply the state-of-the-art methodologies (enhanced sampling methods) to establish a solid and accurate enough computational strategy for drug release simulations from clays and apply it to the systems of relevance according to the World Health Organization. With the work carried out in this project, we have developed a viable computational strategy using as a model praziquantel and montmorillonite clay as drug and excipient, respectively, that can be applied in other drug release simulations. By applying this strategy, we obtain the drug release time, rate, and diffusion coefficient, as well as the mechanism of the drug release from the excipient. These studies open a new field of research aimed at improving the design and development of new drugs in a faster and more efficient way.
Data: CORDIS, © European Union
Project objective
Finding the most efficient and cheapest drug-excipient complex for an increased or modified release kinetics profile of drugs in the body is a current technological challenge in the pharmaceutical industry, especially to improve the treatment of high prevalence and third-country diseases. In this context, it is highly interesting the research on adsorption and diffusion of organic compounds in the surface or internal spaces of clays or related systems. The aim of this proposal is to apply the unique enhanced sampling metadynamics computational tool to properly analyse the processes involved at the nanometric scale, leading not only to rational principles but also to predictions of the pharmaceutical properties. Initially, a computational strategy based on metadynamics simulations will be defined to reproduce known drug release kinetics in drug-clay complexes. A program to automatize all the computations and data management (METADRUG) will be developed after that and in a subsequent step it will be applied to predict unknown release kinetics of relevant drugs from laminar, porous and nanotubular clays. The overall results shall allow determining the clay structural parameters and drug-clay interactions which modulate the release energetics, contributing to the development of new drug delivery systems and novel analysis processed in pharmaceutical technology. The comprehension and accurate prediction of drug increased or modified release phenomena will contribute in this manner to the EU to gain a competitive edge in this area. By means of the proposed project, the fellow will reach a great expertise in the field of Theoretical and Computational Chemistry by strengthening her skills in the use of classical and quantum chemistry methods, acquiring experience with the employment of metadynamics approaches, and learning about programming in Lammps and Plumed. The fellowship will also allow the applicant to develop a promising scientific career to the European level.
Original text from CORDIS.
Participants
- FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA · GenovaCoordinatorItaly
Links
Data: CORDIS, © European Union