Friday, May 26, 2017

PolySciTech PS-PLA and PLA used in development of protein-loaded nanoparticles to study polymer-protein interactions

Proteins are a class of biopolymers which serve a multitude of critical functions within living organisms. Some proteins, such as collagen and keratin, provide mechanical support while others act as enzymes performing critical processes such as cellular metabolism, signaling, membrane transport. Because of their many biochemical interactions, protein-based medicines hold great promise for treating a wide range of diseases. Proteins are long biopolymers that are folded into a specific 3D orientation by a series of intramolecular forces, some of which are more delicate than others. The exact shape of the fold is critical to how the protein functions and if the protein is unfolded it, typically, can never be folded back into the same shape it was again. A simple, everyday example of this is cooking an egg. As an egg is heated, the proteins in the egg transition from folded into linear forms and link onto one another aggregating into insoluble crosslinked gels. In this way, the proteins transition from the clear, viscous fluid of a freshly cracked egg into the white solid gel associated with a well cooked egg. Similarly, many industrial and laboratory practices such as processing with organic solvents, high temperatures, etc. can cause denaturation rendering the protein useless. This, in addition to the high water-solubility of proteins, makes generating controlled-delivery systems for them particularly challenging. Recently, researchers from University of Washington utilized PolySciTech ( PS-PLA (PolyVivo AK042) and Polylactide to make nanoparticles loaded with albumin to study the interaction between polymers and proteins for drug-delivery applications. This research holds promise for enabling the development of a wide array of controlled-delivery systems of protein-based drugs. Read more: Smith, Josh, Kayla G. Sprenger, Rick Liao, Andrea Joseph, Elizabeth Nance, and Jim Pfaendtner. "Determining dominant driving forces affecting controlled protein release from polymeric nanoparticles." Biointerphases 12, no. 2 (2017): 02D412.

“ABSTRACT: 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.”
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