Abstract
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.
Highlights
In the past few decades, nanomaterials have emerged as a research field with a very broad range of applications in areas such as chemistry, physics, biology, medicine and pharmaceutical science [1,2,3,4,5,6]
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We investigated the behavior of different molecules interacting with self-assembling Poly(lactic acid) (PLA) NPs, using both biochemistry approaches and molecular modeling tools
Summary
In the past few decades, nanomaterials have emerged as a research field with a very broad range of applications in areas such as chemistry, physics, biology, medicine and pharmaceutical science [1,2,3,4,5,6]. In the particular field of drug delivery, NPs provide several advantages, including (1) improved water-solubility of poorly soluble drugs [7,8,9], (2) enhanced drug stability in physiological environments [10,11,12], (3) controlled and sustained drug release [13,14,15,16] and (4) enhanced bioavailability [17,18,19]. Such particles are commonly made of non-toxic, amphiphilic, self-assembling block polymers. This makes biodegradable NPs ideal vectors for drug and protein delivery, and excellent candidates for the future of vaccine administration [22,23,24]
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