New Orleans, Louisiana
June 26, 2016
June 26, 2016
August 28, 2016
Many modern protein and gene based therapies require sophisticated drug delivery systems to regulate the tissue concentration of therapies over time and in specific anatomical locations. Polymer systems have received significant interest as delivery vehicles for releasing therapies at a controlled rate. The rate of drug delivery is influenced by diffusion through polymer matrices, osmosis and polymer degradation. Thus, the design of polymer drug delivery systems requires an understanding of both material properties and fundamental mass transport principles. One polymer that has garnered significant interest in drug delivery applications is alginate, a naturally occurring polysaccharide found in algae. Alginate can be used to encapsulate proteins and small molecules by extruding droplets of alginate/protein solution into a bath of calcium chloride. Divalent calcium cations form bridges with adjacent alginate chains through ionic interactions, which creates an insoluble alginate matrix with a spherical geometry. The encapsulated protein is delivered from the alginate system via diffusion when placed in an aqueous environment.
A multi-week laboratory was adapted from previous work to enable students to experimentally measure and analyze controlled release from an alginate polymer system and investigate the biological effects of drug release. In the first week, a red-dye was used as a model drug and release from alginate beads into an aqueous solution was quantified with spectrophotometry over the course of 60 minutes. The effect of initial dye concentration and alginate composition on the release profile was investigated. In the second week, fluorescently labeled bovine serum albumin (FITC-BSA) was used as a model protein therapy and the release was quantified with fluorescence spectroscopy over the course of several days. Students generated a standard curve for a FITC-BSA concentration range of 0.005-0.1 mg/ml and determined the maximum FITC-BSA loading in alginate beads by dissolving polymers in sodium citrate and measuring the fluorescence of the surrounding solution. A mathematical model for diffusion in spherical coordinates was used to investigate the effect of alginate composition and initial FITC-BSA load on the diffusion coefficient in the polymer system. In the third week, a composite polymer system was fabricated with alginate and chitosan. The relationship between individual and composite polymer properties and BSA-FITC release profiles was investigated. Additionally, the diffusion coefficient in the composite materials was estimated.
The multi-week laboratory provides students an opportunity to investigate the effect of molecular size, drug concentration, and polymer composition on the rate of drug delivery from a non-degrading polymer. Additionally, mathematical models are employed to demonstrate the application of fundamental transport phenomena to controlled release drug delivery. In the future, an additional component of the lab will be developed that is focused on the biological effects of protein delivery, including basic cell function assays to evaluate cellular responses to mitogenic and chemotactic stimuli.
Anderson, C. R. (2016, June), Development of a Multi-week Drug Delivery Laboratory for Chemical Engineers Paper presented at 2016 ASEE Annual Conference & Exposition, New Orleans, Louisiana. 10.18260/p.26806
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