Computational and Mathematical Methods in Medicine
Volume 10 (2009), Issue 1, Pages 49-70
Original Article

Computer-Aided Design of Nanocapsules for Therapeutic Delivery

Center for Cell and Virus Theory, Department of Chemistry, Indiana University, Bloomington, IN 47405, USA

Received 21 December 2007; Accepted 22 April 2008

Copyright © 2009 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The design of nanocapsules for targeted delivery of therapeutics presents many, often seemingly self-contradictory, constraints. An algorithm for predicting the physico-chemical characteristics of nanocapsule delivery and payload release using a novel all-atom, multiscale technique is presented. This computational method preserves key atomic-scale behaviours needed to make predictions of interactions of functionalized nanocapsules with the cell surface receptors, drug, siRNA, gene or other payload. We show how to introduce a variety of order parameters with distinct character to enable a multiscale analysis of a complex system. The all-atom formulation allows for the use of an interatomic force field, making the approach universal and avoiding recalibration with each new application. Alternatively, key parameters, which minimize the need for calibration, are also identified. Simultaneously, the methodology enables predictions of the supra-nanometer-scale behaviour, such as structural transitions and disassembly of the nanocapsule accompanying timed payload release or due to premature degradation. The final result is a Fokker–Planck equation governing the rate of stochastic payload release and structural changes and migration accompanying it. A novel “salt shaker” effect that underlies fluctuation-enhancement of payload delivery is presented. Prospects for computer-aided design of nanocapsule delivery system are discussed.