ABSTRACT Polymeric gels that undergo deformation upon appropriate changes in pH or temperature have considerable promise as drug delivery... Show moreABSTRACT Polymeric gels that undergo deformation upon appropriate changes in pH or temperature have considerable promise as drug delivery vehicles. Uptake of drug macromolecules into swelling and non-swelling cylindrical and spherical gels and release of drug macromolecules from deswelling and non-deforming gels into a target fluid are investigated here. A mathematical model for gel-solution composite, a composite of a distributed parameter system (gel spheres or cylinders) and a lumped parameter system (surrounding solution), is developed. The polymer network displacement in swelling/deswelling gels is described by a stress diffusion coupling model. The analytical solution for network displacement is used to predict solvent intake by swelling gels, solvent efflux from deswelling gels, and changes in pressure, porosity and effective drug diffusivity resulting from network displacement. These in turn influence drug uptake during and after gel swelling and drug release from gel during and after gel deswelling. Numerical results illustrate benefits of gel swelling for drug loading and merits of different modes of drug release. Also, the attempt is made to analyze he effect of gel mesh size on the loading and release of large molecular weight drugs. Comparisons are made, as concerns drug uptake and drug release, with gels not subject to deformation. As a special case of application of the above developed model, we tried to simulate drug delivery to the human eye. Since, the therapeutic modalities for posterioreye diseases involve mostly interventions through the anterior eye, which are difficult for physicians and patients alike, sustained drug delivery to the posterior eye is gaining importance. A study for sustained delivery of an anti-VEGF agent (IgG) to the posterior eye from an implant, made of poly(N-isopropylacrylamide) (NIPAM) and placed episclerally, is presented. The model developed in the study is used to simulate the phase transition of the implant made of a thermo-sensitive polymer. The study xvii utilizes compartments for various eye tissues, with individual compartments considered to be completely mixed and drug transport between compartments occurring by one-dimensional diffusion. Further implementation of this model to predict drug concentrations in the eye tissues to arrive at optimum drug loading conditions is also presented here. Ph.D. in Chemical Engineering, July 2011 Show less
