1 research outputs found
Injectable On-Demand Pulsatile Drug Delivery Hydrogels Using Alternating Magnetic Field-Triggered Polymer Glass Transitions
Remote-controlled pulsatile or staged
release has significant potential in a wide range of therapeutic treatments.
However, most current approaches are hindered by the low resolution
between the on- and off-states of drug release and the need for surgical
implantation of larger controlled-release devices. Herein, we describe
a method that addresses these limitations by combining injectable
hydrogels, superparamagnetic iron oxide nanoparticles (SPIONs) that
heat when exposed to an alternating magnetic field (AMF), and polymeric
nanoparticles with a glass transition temperature (Tg) just above physiological temperature. Miniemulsion
polymerization was used to fabricate poly(methyl methacrylate-co-butyl methacrylate) (p(MMA-co-BMA))
nanoparticles loaded with a model hydrophobic drug and tuned to have
a Tg value just above physiological temperature
(∼43 °C). Co-encapsulation of these drug-loaded nanoparticles
with SPIONs inside a carbohydrate-based injectable hydrogel matrix
(formed by rapid hydrazone cross-linking chemistry) enables injection
and immobilization of the nanoparticles at the target site. Temperature
cycling facilitated a 2.5:1 to 6:1 on/off rhodamine release ratio
when the nanocomposites were switched between 37 and 45 °C; release
was similarly enhanced by exposing the nanocomposite hydrogel to an
AMF to drive heating, with enhanced release upon pulsing observed
even 1 week after injection. Coupled with the apparent cytocompatibility
of all of the nanocomposite components, these injectable nanocomposite
hydrogels are promising as minimally invasive but remotely actuated
release delivery vehicles capable of complex release kinetics with
high on–off resolution