(193aj) Structure of Amphipathic Dendrons in Non-Polar Environments

Structure
of Amphipathic Dendrons in Non-Polar Environments

Yang Wang^†, Karolina A. Kosakowska^‡, Scott M. Grayson^‡, and
Henry S. Ashbaugh^†

† Department of Chemical and Biomolecular Engineering, Tulane
University, New Orleans, LA

‡ Department of Chemistry, Tulane University,
New Orleans, LA

The design of drug delivery vehicles
that maintain their structural integrity is important for the efficient
delivery of drugs. In transdermal drug delivery, for example, the stratum
corneum is the most significant barrier to the delivery of polar drugs since it
makes a non-polar environment. Amphiphilic polymers with polyethylene glycol (PEG)
based core and dodecyl group based peripheral dendrons are potential delivery
vehicle for polar drugs, because they can form unimolecular micelles with a
polar core and a non-polar shell to adapt non-polar environment. The conformational
properties and aggregation of these polymers can be impacted by their
architectures determined by 3 architectural variables: The size of their PEG
cores; he degree of core branching (Linear, Dimer, Star); and the degree of
peripheral branching. Predicting the impact of these variables on the delivery
properties of these polymer is crucial for the efficient synthesis of dendrons.
Here we present a coarse-grained molecular dynamics simulation study of amphipathic
dendrons with different polymer architectures in toluene to investigate the
impact of these variables on the properties of unimolecular micelles. We
simulate the experimentally relevant range of PEG core sizes (500 g/mol to 5000 g/mol), core
architectures (linear, dimer, and star), and peripheral branching (from
generation 0 to 5). From our simulations we are able to develop scaling relations
for the fraction of PEG exposed to the solvent, which is expected to correlate
with the propensity of these polymers to aggregate in solution. Good agreement
is found between the experimental results for dendron aggregate dimensions and
core exposure.