Modeling Mass Transfer from Carmustine-Loaded Polymeric Implants for Malignant Gliomas

Abstract

Significant advances in the encapsulation and release of drugs from degradable polymers have led to the Food and Drug Administration approval of Gliadel wafers for controlled local delivery of the chemotherapeutic drug carmustine to high-grade gliomas following surgical resection. Due to the localized nature of the delivery method, no pharmacokinetic measurements have been taken in humans. Rather, pharmacokinetic studies in animals and associated modeling have indicated the capability of carmustine to be delivered in high concentrations within millimeters from the implant site over approximately 5 days. Mathematical models have indicated that diffusion has a primary role in transport, which may be complemented by enhanced fluid convection from postsurgical edema in the initial 3 days following implantation. Carmustine's penetration distance is also presumably limited by its lipophilicity and permeability in the capillaries. This review discusses the mathematical models that have been used to predict the release and distribution of carmustine from a polymeric implant. These models provide a theoretical framework for greater understanding of systems for localized drug delivery while highlighting factors that should be considered in clinical applications. In effect, Gliadel wafers and similar drug delivery implants can be optimized with reduction in required time and resources with such a quantitative and integrative approach.