Search for: All records

Abstract Maintaining safe and potent pharmaceutical drug levels is often challenging. Multidomain peptides (MDPs) assemble into supramolecular hydrogels with a well-defined, highly porous nanostructure that makes them attractive for drug delivery, yet their ability to extend release is typically limited by rapid drug diffusion. To overcome this challenge, we developed self-assembling boronate ester release (SABER) MDPs capable of engaging in dynamic covalent bonding with payloads containing boronic acids (BAs). As examples, we demonstrate that SABER hydrogels can prolong the release of five BA-containing small-molecule drugs as well as BA-modified insulin and antibodies. Pharmacokinetic studies revealed that SABER hydrogels extended the therapeutic effect of ganfeborole from days to weeks, preventingMycobacterium tuberculosisgrowth better than repeated oral administration in an infection model. Similarly, SABER hydrogels extended insulin activity, maintaining normoglycemia for six days in diabetic mice after a single injection. These results suggest that SABER hydrogels present broad potential for clinical translation. 

The dynamic stability of a cantilevered beam actuated by a nonconservative follower force has previously been studied for its interesting dynamical properties and its applications to engineering designs such as thrusters. However, most of the literature considers a linear model. A modest number of papers consider a nonlinear model. Here, a system of nonlinear equations is derived from a new energy approach for an inextensible cantilevered beam with a follower force acting upon it. The equations are solved in time, and the agreement is shown with published results for the critical force including the effects of damping (as determined by a linear model). This model readily allows the determination of both in-plane and out-of-plane deflections as well as the constraint force. With this novel transparency into the system dynamics, the nonlinear postcritical limit cycle oscillations (LCO) are studied including a concentration on the force which enforces the inextensibility constraint.