Stimuli-responsive polymeric nanoparticles for drug delivery platforms enhance on-demand drug release, drug loading capacity, and drug efficacy in response to the biological environment. The stability of polymeric nanoparticles plays a critical role in translational research. Kinetically-arrested nanoparticles are advantageous for their high loading capacity and ability to incorporate a variety of different solutes (e.g., drug cocktails or, drugs and imaging agents). We hypothesize that the stability of nanoparticles produced by a rapid assembly method can be further enhanced with the incorporation of dynamic-covalent bonds at the core/shell interlayer. Herein, we discuss the use of boronic acid/diol interactions to enhance nanoparticle stability and endow pH-responsiveness to these constructs. We have examined this on nanoparticles stabilized with toothbrush and bottlebrush triblock copolymers of poly(D,L-lactide), poly(2-methacryloyloxyethyl phosphorylcholine), and boronic acid-containing blocks. These were synthesized through a combination of ring-opening, reversible addition−fragmentation chain-transfer (RAFT), and atom transfer radical polymerizations (ATRP). These triblock copolymers were formulated into interlayer-crosslinked nanoparticles (ICN) by post stabilization with diol/catechol stabilizers such as tannic acid and poly(dopamine-<i>b</i>-MPC) using a four-stream vortex mixer. In addition, various solutes as model drugs (rose bengal lactone and probucol) were encapsulated into the ICN. ICN shape, size, and stability were characterized by a combination of DLS, SLS, and TEM. Additionally, we examined the stimuli-responsive properties of ICN by release kinetics in basic (pH 9.2), neutral (pH 7.4), and acidic (pH 6.4 and 5.5) media and related the differences in release profiles and particle stability with the properties of the stabilizers. In summary, our results suggest that dynamic-covalent interactions at the interface enhance the stability of drug-loaded ICN, and release drugs in a pH-, and stabilizer-dependent manner. Therefore, ICN has tremendous potential for stimuli-responsive drug delivery application.

Reversible interlayer boronic acid/diol crosslinked bottlebrush nanoparticles for drug delivery

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.