Quantitative Detection of PLGA Nanoparticle Degradation in Tissues following Intravenous Administration

The biodegradable polymer poly­(lactic-<i>co</i>-glycolic) acid (PLGA) has been extensively utilized and investigated as a drug delivery system. Although <i>in vivo</i> biodegradation (at specific administration sites only) of PLGA-based drug delivery constructs, such as foams and microparticles, has been studied, quantitative <i>in vivo</i> biodegradation of distributed polymer nanoparticles has not been accomplished and is quintessential for designing formulations to achieve desired pharmacokinetic properties of a drug in a target tissue. We determined the <i>in vivo</i> degradation kinetics of PLGA nanoparticles, of two sizes, distributed in liver, spleen, and lungs following intravenous administration. In addition, we simultaneously determined the amount of polymer in tissues. Nanoparticle degradation <i>in vitro</i> and <i>in vivo</i> appears to be a first-order process, and useful correlations were obtained between <i>in vitro</i> and <i>in vivo</i> tissue degradation of the nanoparticles. The ability to detect <i>in vivo</i> degradation and biodistribution of polymer nanoparticles is a significant milestone for the rational design of degradable nanoparticle-based drug delivery systems capable of delivering the therapeutic agent in a closely predictable manner to target tissue