Control of drug release rate by partition effect via drug immobilization.
Date of Issue2011
School of Mechanical and Aerospace Engineering
New technology and clearer biological insight have led to new classes of therapeutic agents; typical examples are antibodies, gene-based drugs, antisense oligonucleotides, virus-like particles, recombinant proteins and hormone. But the potency and activity of these biotechnological agents are often thwarted by the wrong or the improperly constructed delivery systems, due to the fact that these agents frequently have short half-lives, poor permeability in membranes, and serious toxicity when delivered systemically in large doses. Drug Delivery Systems (DDS) are designed to deliver hormones and other protein drugs so as to maximize their therapeutic effect. Precise control of the drug release rate is crucial in such systems; yet it is not achieved with reasonable flexibility and accuracy. One of the reasons behind the imprecise control is that some of the important factors governing drug release rate are not actively controlled. Partition coefficient is one of such factors. The objective of our project is to provide a method to actively control the partition coefficient so as to more precisely control the overall drug release rate for a better therapeutic outcome. It is hypothesized that the drug partition coefficient can be tailored by immobilizing the same drug in the DDS due to the chemical potential contribution. It is found that the immobilization of the model drug (Bovine Serum Albumin, BSA) in the DDS results in a slower release rate for the un-immobilized drug (BSA). The reduction in release rate can be attributed to partition coefficient reduction, and the mathematical equation that depicts this relation between partition coefficient and the amount of immobilization is derived based on first-principle thermodynamic analysis.