Modeling Drug Delivery for Design of PLGA Microparticles

Ashlee N. Ford, Chemical & Biomolecular Engineering, University of Illinois, 600 South Mathews Avenue, 201 Roger Adams Laboratory, Box C-3, Urbana, IL 61801-3602, Daniel W. Pack, Chemical & Biomolecular Engineering, University of Illinois Urbana-Champaign, 600 S. Mathews, Box C-3 MC 712, Urbana, IL 61801, and Richard D. Braatz, Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Box C-3, 293 Roger Adams Laboratory, Urbana, IL 61801-3602.

The objective of this project is to develop a mechanistic model that is sufficiently accurate for predicting the drug release behavior that the model can be used for the optimal design of controlled-release drug delivery devices. A model is described for capturing the heterogeneity of autocatalytic degradation of poly(lactic-co-glycolic acid) (PLGA) polymer microspheres. The model is extended to apply to core-shell microparticles and microcapsules, which are important options for encapsulating drugs for delivery in a multi-stage pulsatile release fashion or for protecting proteins from being deactivated by suspension in an aqueous core for time-delayed delivery after polymer microcapsule degradation. The predictions for the core-shell microparticles and microcapsules are compared to experimental results. These mechanistic models contain no empirical parameters such as time-varying effective diffusivities--all model parameters are true physicochemical parameters taken from calculations of transport through pores or direct observation of depolymerization in well-characterized well-mixed reactors.

This poster describes the use of the mechanistic model to optimally design biodegradable polymeric microparticles for controlled release, which can be made reproducibly by the precision particle fabrication technique that yields highly uniform distributions with tight control of the specific sizes and thicknesses of core-shell microparticles and microcapsules. Changing the design variables of core diameter and shell thickness along with the distribution of molecular weights and pore sizes enables the design of microparticles to produce a large spectrum of obtainable release profiles. These profiles include zeroth-order release and pulsatile release with a range of shapes for the individual pulses. The model also determines the pH as a function of position within the microparticle, which can be used to design microparticles that limit the pH to ranges in which the released molecule is stable. The model can also be used to compute an optimal distribution of microparticles, which can be relevant when restrictions are placed on the microenvironment within the microparticles, such as limits to the pH.