posted on 2019-01-28, 18:48authored byJeffrey
C. Foster, Ryan J. Carrazzone, Nathan J. Spear, Scott C. Radzinski, Kyle J. Arrington, John B. Matson
Drug
delivery from polymer micelles has been widely studied, but
methods to precisely tune rates of drug release from micelles are
limited. Here, the mobility of hydrophobic micelle cores was varied
to tune the rate at which a covalently bound drug was released. This
concept was applied to cysteine-triggered release of hydrogen sulfide
(H2S), a signaling gas with therapeutic potential. In this
system, thiol-triggered H2S donor molecules were covalently
linked to the hydrophobic blocks of self-assembled polymer amphiphiles.
Because release of H2S is triggered by cysteine, diffusion
of cysteine into the hydrophobic micelle core was hypothesized to
control the rate of release. We confirmed this hypothesis by carrying
out release experiments from H2S-releasing micelles in
varying compositions of EtOH/H2O. Higher EtOH concentrations
caused the micelles to swell, facilitating diffusion in and out of
their hydrophobic cores and leading to faster H2S release
from the micelles. To achieve a similar effect without addition of
organic solvent, we prepared micelles with varying core mobility via
incorporation of a plasticizing comonomer in the core-forming block.
The glass transition temperature (Tg)
of the core block could therefore be precisely varied by changing
the amount of the plasticizing comonomer in the polymer. In aqueous
solution under identical conditions, the release rate of H2S varied over 20-fold (t1/2 = 0.18–4.2
h), with the lowest Tg hydrophobic block
resulting in the fastest H2S release. This method of modulating
release kinetics from polymer micelles by tuning core mobility may
be applicable to many types of physically encapsulated and covalently
linked small molecules in a variety of drug delivery systems.