Determining dominant driving forces affecting controlled protein release frompolymeric nanoparticles

摘要

Enzymes play a critical role in many applications in biology and medicine as potential therapeutics. One specific area of interest is enzyme encapsulation in polymer nanostructures, which have applications in drug delivery and catalysis. A detailed understanding of the mechanisms governing protein/polymer interactions is crucial for optimizing the performance of these complex systems for different applications. Using a combined computational and experimental approach, this study aims to quantify the relative importance of molecular and mesoscale driving forces to protein release from polymeric nanoparticles. Classical molecular dynamics (MD) simulations have been performed on bovine serum albumin (BSA) in aqueous solutions with oligomeric surrogates of poly(lactic-co-glycolic acid) copolymer, poly(styrene)-poly(lactic acid) copolymer, and poly(lactic acid). The simulated strength and location of polymer surrogate binding to the surface of BSA have been compared to experimental BSA release rates from nanoparticles formulated withthese same polymers. Results indicate that the self-interaction tendencies of the polymersurrogates and other macroscale properties may play governing roles in protein release. AdditionalMD simulationsof BSA in solutionwith poly(styrene)-acrylate copolymer reveal the possibility of enhanced control over the enzymeencapsulation process by tuning polymer self-interaction. Last, the authors findconsistent proteinsurface binding preferences across simulations performed with polymer surrogates ofvarying lengths, demonstrating that protein/polymerinteractions canbe understood in part by studying the interactions and affinity of proteins with small polymersurrogates in solution.