Combined Numerical and Experimental Studies for Release Kinetics of Embedded Drugs from Deformable Engineered Vectors in Response to External Stimuli, 20-R8305
Principal Investigators
Hakan Başağaoğlu
Gianny Rossini
John T. Carrola Jr.
Inclusive Dates: 01/04/12 – Current
Background — The main objective of this study is to develop a novel two- and three-dimensional numerical model to simulate (i) the fate and transport of nano- to micron size deformable capsules with embedded nanodrugs; (ii) releases of embedded nanodrugs in response to cumulative mass erosion on the particle surface induced by dynamic flow shear rates; and (iii) local concentrations of the released nanodrugs along the flow pathways of deformable particles. To our knowledge, there has been no numerical model developed with these capabilities. The project also includes experimental tasks focusing on (i) fabrication of deformable capsules, (ii) flexibility measurements of the capsules, and (iii) release kinetics of embedded drugs under controlled shear rates. To date, only limited and incomplete experimental data on release kinetics of embedded drugs from deformable particles have been presented in the literature. In this project, experimental data will be used to validate and enhance the numerical model.
Approach — A new numerical model, based on the lattice-Boltzmann method, will be developed to simulate trajectories of deformable particles in a transient flow field. As part of this model, a new algorithm, based on the Catmull-Rom Splines method and topological relations, will be developed to keep track of all interior and exterior boundary nodes in the vicinity of an arbitrarily deformed surface of a mobile particle, which will be central to deformable particle-fluid hydrodynamics calculations. Moreover, a new equation based on existing literature data will be formulated to calculate shear-induced cumulative mass erosion rates on deformable particle surfaces as a function of local shear stress and flow velocity at particle boundary nodes. To simulate local concentrations of the released nanodrugs from deformable particles, a stochastic-differential equation will be formulated. The new algorithm and the new equations will be integrated into the master code, which we developed previously. For the experimental tasks, new capsules (liposomes) will be developed with tunable flexibilities using different surfactants. The flexibility (deformability) test will be performed using a Lipex extruder to quantify flexibility indices. Release kinetics of embedded drugs will be quantified after flow pressure generated by circulating the sample using a peristaltic pump through narrow capillary tubing mimicking the conditions of in vivo capillary blood circulation. Experimental data on the release kinetics of Fluorescein from deformable capsules will be used for model validation.
Accomplishments — SwRI researchers successfully developed a new algorithm, a Triangular Caging algorithm, as a stand-alone module to locate all interior and exterior boundary nodes of an arbitrarily deformable surface of a mobile particle. A new equation was formulated and coded as a standalone module to simulate shear-induced release kinetics of nanodrugs from mobile deformable particles. For the experimental tasks, surfactants were used to successfully fabricate three different types of flexible capsules, each with different degrees of flexibility, and measured their flexibility indices in repeatable experiments. Findings were presented November 2 at the American Society of Mechanical Engineering Conference in Houston. After completing scoping analysis, proposals will be prepared for the Defense Advanced Research Projects Agency and the National Institutes of Health.
