Molecular Dynamics Studies of Poly(Lactic Acid) Nanoparticles and Their Interactions with Vitamin E and TLR Agonists Pam<sub>1</sub>CSK<sub>4</sub> and Pam<sub>3</sub>CSK<sub>4</sub>
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...
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| Format: | Article |
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MDPI AG
2020-11-01
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| Series: | Nanomaterials |
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| Online Access: | https://www.mdpi.com/2079-4991/10/11/2209 |
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| author | Simon Megy Stephanie Aguero David Da Costa Myriam Lamrayah Morgane Berthet Charlotte Primard Bernard Verrier Raphael Terreux |
| author_facet | Simon Megy Stephanie Aguero David Da Costa Myriam Lamrayah Morgane Berthet Charlotte Primard Bernard Verrier Raphael Terreux |
| author_sort | Simon Megy |
| collection | DOAJ |
| description | 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 Pam<sub>1</sub>CSK<sub>4</sub> and Pam<sub>3</sub>CSK<sub>4</sub>, 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, Pam<sub>1</sub>CSK<sub>4</sub> and Pam<sub>3</sub>CSK<sub>4</sub> 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. |
| first_indexed | 2024-03-10T15:04:25Z |
| format | Article |
| id | doaj.art-c5d6f9dec30d4c5084a0ab39121db06b |
| institution | Directory Open Access Journal |
| issn | 2079-4991 |
| language | English |
| last_indexed | 2024-03-10T15:04:25Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nanomaterials |
| spelling | doaj.art-c5d6f9dec30d4c5084a0ab39121db06b2023-11-20T19:55:57ZengMDPI AGNanomaterials2079-49912020-11-011011220910.3390/nano10112209Molecular Dynamics Studies of Poly(Lactic Acid) Nanoparticles and Their Interactions with Vitamin E and TLR Agonists Pam<sub>1</sub>CSK<sub>4</sub> and Pam<sub>3</sub>CSK<sub>4</sub>Simon Megy0Stephanie Aguero1David Da Costa2Myriam Lamrayah3Morgane Berthet4Charlotte Primard5Bernard Verrier6Raphael Terreux7PRABI (Pôle Rhône-Alpes de Bioinformatique), Lyon Gerland, UMR5305, LBTI, IBCP, Lyon 1 University, 7 Passage du Vercors, 69367 Lyon CEDEX 07, FrancePRABI (Pôle Rhône-Alpes de Bioinformatique), Lyon Gerland, UMR5305, LBTI, IBCP, Lyon 1 University, 7 Passage du Vercors, 69367 Lyon CEDEX 07, FranceColloidal Vectors and Tissue Transport, UMR5305, LBTI, IBCP, Lyon 1 University, 7 Passage du Vercors, 69367 Lyon CEDEX 07, FranceColloidal Vectors and Tissue Transport, UMR5305, LBTI, IBCP, Lyon 1 University, 7 Passage du Vercors, 69367 Lyon CEDEX 07, FranceColloidal Vectors and Tissue Transport, UMR5305, LBTI, IBCP, Lyon 1 University, 7 Passage du Vercors, 69367 Lyon CEDEX 07, FranceAdjuvatis, 7 Passage du Vercors, 69007 Lyon, FranceColloidal Vectors and Tissue Transport, UMR5305, LBTI, IBCP, Lyon 1 University, 7 Passage du Vercors, 69367 Lyon CEDEX 07, FrancePRABI (Pôle Rhône-Alpes de Bioinformatique), Lyon Gerland, UMR5305, LBTI, IBCP, Lyon 1 University, 7 Passage du Vercors, 69367 Lyon CEDEX 07, FrancePoly(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 Pam<sub>1</sub>CSK<sub>4</sub> and Pam<sub>3</sub>CSK<sub>4</sub>, 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, Pam<sub>1</sub>CSK<sub>4</sub> and Pam<sub>3</sub>CSK<sub>4</sub> 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.https://www.mdpi.com/2079-4991/10/11/2209polylactic acidnanoparticlesmolecular dynamicsdissipative particle dynamicsPam<sub>3</sub>CSK<sub>4</sub>Pam<sub>1</sub>CSK<sub>4</sub> |
| spellingShingle | Simon Megy Stephanie Aguero David Da Costa Myriam Lamrayah Morgane Berthet Charlotte Primard Bernard Verrier Raphael Terreux Molecular Dynamics Studies of Poly(Lactic Acid) Nanoparticles and Their Interactions with Vitamin E and TLR Agonists Pam<sub>1</sub>CSK<sub>4</sub> and Pam<sub>3</sub>CSK<sub>4</sub> Nanomaterials polylactic acid nanoparticles molecular dynamics dissipative particle dynamics Pam<sub>3</sub>CSK<sub>4</sub> Pam<sub>1</sub>CSK<sub>4</sub> |
| title | Molecular Dynamics Studies of Poly(Lactic Acid) Nanoparticles and Their Interactions with Vitamin E and TLR Agonists Pam<sub>1</sub>CSK<sub>4</sub> and Pam<sub>3</sub>CSK<sub>4</sub> |
| title_full | Molecular Dynamics Studies of Poly(Lactic Acid) Nanoparticles and Their Interactions with Vitamin E and TLR Agonists Pam<sub>1</sub>CSK<sub>4</sub> and Pam<sub>3</sub>CSK<sub>4</sub> |
| title_fullStr | Molecular Dynamics Studies of Poly(Lactic Acid) Nanoparticles and Their Interactions with Vitamin E and TLR Agonists Pam<sub>1</sub>CSK<sub>4</sub> and Pam<sub>3</sub>CSK<sub>4</sub> |
| title_full_unstemmed | Molecular Dynamics Studies of Poly(Lactic Acid) Nanoparticles and Their Interactions with Vitamin E and TLR Agonists Pam<sub>1</sub>CSK<sub>4</sub> and Pam<sub>3</sub>CSK<sub>4</sub> |
| title_short | Molecular Dynamics Studies of Poly(Lactic Acid) Nanoparticles and Their Interactions with Vitamin E and TLR Agonists Pam<sub>1</sub>CSK<sub>4</sub> and Pam<sub>3</sub>CSK<sub>4</sub> |
| title_sort | molecular dynamics studies of poly lactic acid nanoparticles and their interactions with vitamin e and tlr agonists pam sub 1 sub csk sub 4 sub and pam sub 3 sub csk sub 4 sub |
| topic | polylactic acid nanoparticles molecular dynamics dissipative particle dynamics Pam<sub>3</sub>CSK<sub>4</sub> Pam<sub>1</sub>CSK<sub>4</sub> |
| url | https://www.mdpi.com/2079-4991/10/11/2209 |
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