(302g) Computational Design of Peptide Containing Poly(ethylene glycol) Brushes for Stimuli Responsive Drug Delivery

Stimuli-responsive biomaterials have used in various biomedical applications, such as carriers/vectors or matrix to facilitate intracellular or extracellular drug and gene delivery. The targeted delivery aspect of the stimuli-responsive carrier is imparted by incorporating chemistries that are able to recognize a specific micro-environment and are sensitive to various factors, such as temperature, pH, ionic strength, electric or magnetic fields, and light. In particular, pH-responsive biomaterials have been exploited to control the delivery of drugs to specific organs, intracellular compartments, cancer cells, site of inflammation or infection characterized by different pHs. One of the limitations in the design of pH-responsive biomaterials is that the contrast between ‘stimulus’ and ‘non-stimulus’ is often small, especially the pH difference between intracellular and extracellular environments. To maximize this contrast, it is important to understand and manipulate the balance between the various inter-molecular forces (e.g. electrostatics, van der Waals), which then allow functional molecules to be reversibly exposed and shielded to the environment in the presence and absence of a stimulus. We use molecular dynamics (MD) simulations to design such a system where the shielding aspect of the stimuli-responsive carrier is imparted by the use of polyethylene glycol (PEG) brush and the pH responsive component is a PEG-tethered oligopeptide that is able to change conformation in response to the change of pH. Using simulations we optimize the features of the PEG brush (e.g. molecular weight, polydispersity, etc.) and oligopeptide sequences and composition, so that the steric forces provided by PEG, compete with the electrostatic forces between peptide, water and PEG, and within the peptide leading to shielded and exposed conformations in the two different pH.