Determining dominant driving forces affecting controlled protein release from polymeric nanoparticles

• Published in: Biointerphases Vol. 12; no. 2; p. 02D412
• Main Authors: Smith, Josh, Sprenger, Kayla G, Liao, Rick, Joseph, Andrea, Nance, Elizabeth, Pfaendtner, Jim
• Format: Journal Article
• Language: English
• Published: United States American Vacuum Society 01-06-2017
• Subjects: Animals; Cattle; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacokinetics; In Focus: Protein Structure at Biointerfaces; Lactic Acid - chemistry; Molecular Dynamics Simulation; Nanoparticles - chemistry; Polyesters - chemistry; Polyglycolic Acid - chemistry; Polystyrenes - chemistry; Serum Albumin, Bovine - chemistry; Serum Albumin, Bovine - pharmacokinetics
• ISSN: 1934-8630; 1559-4106
• DOI: 10.1116/1.4983154

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 with these same polymers. Results indicate that the self-interaction tendencies of the polymer surrogates and other macroscale properties may play governing roles in protein release. Additional MD simulations of BSA in solution with poly(styrene)-acrylate copolymer reveal the possibility of enhanced control over the enzyme encapsulation process by tuning polymer self-interaction. Last, the authors find consistent protein surface binding preferences across simulations performed with polymer surrogates of varying lengths, demonstrating that protein/polymer interactions can be understood in part by studying the interactions and affinity of proteins with small polymer surrogates in solution.