Molecular Dynamics Studies of Poly(Lactic Acid) Nanoparticles and Their Interactions with Vitamin E and TLR Agonists Pam₁CSK₄and Pam₃CSK₄

• Main Authors: Simon Megy, Stephanie Aguero, David Da Costa, Myriam Lamrayah, Morgane Berthet, Charlotte Primard, Bernard Verrier, Raphael Terreux
• Format: Article
• Language: English
• Published: MDPI AG 2020-11-01
• Series: Nanomaterials
• Subjects: polylactic acid; nanoparticles; molecular dynamics; dissipative particle dynamics; Pam₃CSK₄; Pam₁CSK₄
• Online Access: https://www.mdpi.com/2079-4991/10/11/2209

Poly(lactic acid) (PLA) nanoparticles (NPs) are widely investigated due to their bioresorbable, biocompatible and low immunogen properties. Interestingly, many recent studies show that they can be efficiently used as drug delivery systems or as adjuvants to enhance vaccine efficacy. Our work focuses on the molecular mechanisms involved during the nanoprecipitation of PLA NPs from concentrated solutions of lactic acid polymeric chains, and their specific interactions with biologically relevant molecules. In this study, we evaluated the ability of a PLA-based nanoparticle drug carrier to vectorize either vitamin E or the Toll-like receptor (TLR) agonists Pam₁CSK₄ and Pam₃CSK₄, which are potent activators of the proinflammatory transcription factor NF-κB. We used dissipative particle dynamics (DPD) to simulate large systems mimicking the nanoprecipitation process for a complete NP. Our results evidenced that after the NP formation, Pam₁CSK₄ and Pam₃CSK₄ molecules end up located on the surface of the particle, interacting with the PLA chains via their fatty acid chains, whereas vitamin E molecules are buried deeper in the core of the particle. Our results allow for a better understanding of the molecular mechanisms responsible for the formation of the PLA NPs and their interactions with biological molecules located either on their surfaces or encapsulated within them. This work should allow for a rapid development of better biodegradable and safe vectorization systems with new drugs in the near future.