Enhancing Nanocarrier Trigger-Sensitivity for Targeted Drug Delivery Application using Ligand-Receptor Residence Time Factor

Abstract

The use of nanocarriers to encapsulate and carry drug molecules to different parts of the body for therapeutic purpose in a controlled and targeted manner has received extensive attention in the literature. To deliver the drug to the targets site, the nanocarrier has to be responsive to triggered-release stimuli. In some scenarios, the trigger stimuli will be externally introduced into the system in which case the nanocarrier must be equipped with a trigger-release mechanism. In the case where the release is initiated by membrane receptor-mediation, the responsiveness of the nanocarrier to the trigger stimuli is crucial. The responsiveness factor is a function of the nanocarrier sensitivity, which is primarily determined by the concentration of the membrane receptors. However, the nanoscale size of the nanocarrier limits the concentration of the receptor it can be equipped with. In this paper, based on the molecular communication (MC) paradigm, an approach that enhances the sensitivity of the nanocarrier to external stimuli is presented. The analytical expressions for the number of trigger molecule-receptor complex, which defines the nanocarrier sensitivity are presented. The effectiveness of the proposed model is investigated using simulation. Results show that the performance of the MC-based targeted drug delivery process is dependent on the sensitivity of the drug-carrying nanocarrier to external stimuli. In this sense, it is shown that the residence time factor can be used to greatly enhance the responsiveness of the nanocarrier to stimuli even at very low membrane receptor and stimuli concentrations.