Computer Modeling of Drug Delivery with Thermosensitive Liposomes in a Realistic Three-Dimensional Geometry.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Pharmacology

Background:

• Thermosensitive liposomes (TSL) offer targeted drug delivery when heated.
• Localized hyperthermia enhances TSL drug release.
• Accurate modeling is crucial for optimizing TSL-based therapies.

Purpose of the Study:

• To create and validate a 3D computer model for simulating TSL-Dox delivery to tumors.
• To compare model predictions with experimental data from phantom and in vivo studies.
• To assess the feasibility of computational modeling for preclinical TSL drug delivery research.

Main Methods:

• 3D scanning of a mouse hind limb and import into finite element modeling software.
• Simulation of localized hyperthermia using a surface probe.
• Coupling of heat transfer and drug delivery models.
• Experimental validation using gel phantoms and in vivo fluorescence imaging in mice.

Main Results:

• The computer model accurately reproduced temperature profiles in phantom experiments (mean error 0.71 °C).
• Simulated localized heating resulted in drug delivery concentrated near the probe.
• Model predictions for drug delivery kinetics correlated well with in vivo experimental data.
• Average tumor temperatures ranged from 34.4-43.4 °C, yielding drug concentrations of 11.8-25.6 µg/g.

Conclusions:

• The developed 3D computational model accurately simulates TSL drug delivery.
• This approach demonstrates feasibility for modeling preclinical drug delivery studies.
• Accurate geometric modeling enhances the predictive power of TSL delivery simulations.