Expansile Nanoparticles: Synthesis, Characterization, And In Vivo Efficacy Of An Acid-responsive Polymeric Drug Delivery System

摘要

Micro- and nanoparticles are being employed for an increasing number of medical applications. In terms of drug delivery applications, these particles are being investigated as a means to increase drug solubility, alter biodistribution, enhance pharmacokinetics, target specific sites, and minimize side effects. These particles, depending on the application, are composed of lipids, proteins, carbohydrate, or hydroxy acid polymers. For example, micro- or nanoparticles composed of poly(lactic-glycolic acid), PLGA, are well studied for drug delivery and represent the prototypical polymer particle. Our efforts are focused on designing new nanoparticle compositions that possess an alternative delivery mechanism whereby a hydrophobic to hydrophilic transition is triggered by a physiologic stimulus resulting in swelling and rapid release of their contents. The synthesis of particles which respond to changes in environmental conditions like pH or temperature is a very promising and active area of research. Here, we report an engineered polymeric nanoparticle that expands several hundred-fold in volume in response to a pH change, going from nanometer to micrometer in diameter and that releases its contents. These expansile nanoparticles loaded with paclitaxel, a poorly water-soluble anticancer drug, prevent establishment of lung cancer in vivo and are superior to the conventional drug delivery method for paclitaxel using Cremophor EL/ethanol.