A voxel-based Monte Carlo model of drug release from bulk eroding nanoparticles.
The use of polymeric nanoparticles as drug delivery devices is becoming increasingly prevalent in a variety of therapeutic applications. Despite their widespread clinical use, the factors influencing the release profiles of nanoparticle-encapsulated drugs are still not quantitatively understood. We present here a new, semi-empirical model of drug release from polymeric nanoparticles using a formulation of dexamethasone encapsulated within poly(lactic-co-glycolic acid) to set model parameters. We introduce a three-dimensional voxel-based framework for Monte Carlo simulations that enables direct investigation of the entire spherical nanoparticle during particle degradation and drug release. Due to implementation of this model at the nanoscale, we utilize assumptions that simplify the model while still allowing multi-phase drug release to be simulated with good correlation to experimental results. In the future, emerging mechanistic understandings of nanoparticle drug release may be integrated into this simulation framework to increase predictive power.
Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
David A
DA
Eavarone
Venkataramanan
V
Soundararajan
Toomas
T
Haller
Ram
R
Sasisekharan
D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D006801:Humans; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000737:chemistry; D008954:Models, Biological; D009010:Monte Carlo Method; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone