ProjektportalMultiscale Molecular Dynamics Simulations of Drug Release from Nanoparticle Surfaces
Terrmin
HT25
Beskrivning
Aim
To investigate drug release mechanisms from various nanoparticle systems using multiscale molecular dynamics (MD) simulations, assessing how factors such as nanoparticle composition, biological fluid interactions, and pH affect release dynamics.
Background
Nanoparticle-based drug delivery systems have emerged as promising tools in targeted therapy, offering precise control over drug localization and release profiles. However, understanding the complex molecular mechanisms governing drug release at nanoscale interfaces requires detailed computational modeling. Multiscale molecular dynamics simulations, which span atomistic to coarse-grained resolutions, enable the exploration of molecular phenomena across biologically relevant timescales, elucidating critical insights into drug-nanoparticle interactions and their responsiveness to environmental conditions.
Methods
o Construction and parameterization of nanoparticle-drug simulation systems (lipid nanoparticle, polymeric).
o Performing multiscale simulations:
• All-atom MD simulations (~3 replicates per NP-drug combination, simulation timescale ~50 ns–200 ns per run).
• Coarse-grained MD simulations (~3 replicates per NP-drug combination, simulation timescale ~200 ns–10 ?s per run).
o Simulation conditions:
• Different nanoparticle materials.
• Multiple environmental conditions.
• Interaction with simplified cell surface models.
o Data analysis:
• Quantitative assessment of drug release kinetics and molecular interactions.
• Statistical analysis to characterize variability across conditions.
My task
The student’s role will include:
• Building and validating at least 2-3 distinct nanoparticle models loaded with model drugs.
• Implementing multiscale MD simulations, performing at least 3 independent replicates per system to ensure statistical robustness.
• Investigating the effects of the environmental factors.
• Analyzing and quantifying drug release kinetics, diffusion coefficients, and interaction energies.
• Comparing outcomes across different levels of simulation detail (atomistic vs. coarse-grained).
Expected results:
This project is anticipated to yield:
• Quantitative characterization of drug release rates from various nanoparticles under distinct biological conditions.
• Identification of key molecular interactions governing the stability and controlled release profiles of drug-loaded nanoparticles.
• Insightful comparisons between atomistic and coarse-grained simulation predictions, validating and refining multiscale modeling approaches for nanoparticle-based drug delivery systems.
Huvudområde
Läkemedelsutveckling
Ämne
Läkemedelsformulering och Molekylär galenisk farmaci
Typ
Beräkningsstudie
Företag
Uppsala University
Ort/Plats
Uppsala
Handledarens namn
Aleksei Kabedev
Handledarens e-post
aleksei.kabedev@uu.se
Institution
Institutionen för farmaci
Program
Masterprogram i läkemedelsmodellering
Kurs
Degree Project in Pharmaceutical Modelling within Pharmaceutics and Biopharmaceutics 45 c - 3FG001
Omfattning/hp
45hp
Hur många studenter kan antagas för detta projekt?
1