Degradation of Polymer-Drug Conjugate Nanoparticles Based on Lactic and Itaconic Acid
Tuberculosis (TB) is still a significant threat to human health. A promising solution is engineering nanoparticulate drug carriers to deliver anti-TB molecules. Itaconic acid (ITA) potentially has anti-TB activity; however, its incorporation in nanoparticles (NP) is challenging. Here we show an appr...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/22/14461 |
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| author | Mai Dang Le Vuong Mohamed Haouas Merve Seray Ural Didier Desmaële Charlotte Martineau-Corcos Ruxandra Gref |
| author_facet | Mai Dang Le Vuong Mohamed Haouas Merve Seray Ural Didier Desmaële Charlotte Martineau-Corcos Ruxandra Gref |
| author_sort | Mai Dang Le Vuong |
| collection | DOAJ |
| description | Tuberculosis (TB) is still a significant threat to human health. A promising solution is engineering nanoparticulate drug carriers to deliver anti-TB molecules. Itaconic acid (ITA) potentially has anti-TB activity; however, its incorporation in nanoparticles (NP) is challenging. Here we show an approach for preparing polymer-ITA conjugate NPs and a methodology for investigating the NP degradation and ITA release mechanism. The conjugate was synthesized by the two-directional growing of polylactic acid (PLA) chains, followed by capping their extremities with ITA. The poly(lactate)-itaconate PLA-ITA was then used to formulate NPs. The degradation and drug release processes of the polymer conjugate NPs were studied qualitatively and quantitatively. The molecular structures of released species were characterized by using liquid NMR spectroscopy and mass spectrometry. We discovered a complex NP hydrolysis process forming diverse oligomers, as well as monomeric lactic acid (LA) and drug ITA. The slow degradation process led to a low release of free drugs, although raising the pH from 5.3 to 7.4 induced a slight increase in the amounts of released products. TEM images showed that bulk erosion is likely to play the primary role in the degradation of PLA-ITA NPs. The overall results and methodology can be of interest for understanding the mechanisms of NP degradation and drug release of this new polymer-drug conjugate system. |
| first_indexed | 2024-03-09T18:15:49Z |
| format | Article |
| id | doaj.art-82c2ce194fe64485aefe29fa5390f925 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T18:15:49Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-82c2ce194fe64485aefe29fa5390f9252023-11-24T08:44:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221446110.3390/ijms232214461Degradation of Polymer-Drug Conjugate Nanoparticles Based on Lactic and Itaconic AcidMai Dang Le Vuong0Mohamed Haouas1Merve Seray Ural2Didier Desmaële3Charlotte Martineau-Corcos4Ruxandra Gref5CNRS, Institut Lavoisier de Versailles, UVSQ, Université Paris-Saclay, 78000 Versailles, FranceCNRS, Institut Lavoisier de Versailles, UVSQ, Université Paris-Saclay, 78000 Versailles, FranceCNRS, Institut des Sciences Moléculaires d’Orsay, Université Paris-Saclay, 91405 Orsay, FranceCNRS, Institut Galien Paris-Saclay, Université Paris-Saclay, 91400 Orsay, FranceCNRS, Institut Lavoisier de Versailles, UVSQ, Université Paris-Saclay, 78000 Versailles, FranceCNRS, Institut des Sciences Moléculaires d’Orsay, Université Paris-Saclay, 91405 Orsay, FranceTuberculosis (TB) is still a significant threat to human health. A promising solution is engineering nanoparticulate drug carriers to deliver anti-TB molecules. Itaconic acid (ITA) potentially has anti-TB activity; however, its incorporation in nanoparticles (NP) is challenging. Here we show an approach for preparing polymer-ITA conjugate NPs and a methodology for investigating the NP degradation and ITA release mechanism. The conjugate was synthesized by the two-directional growing of polylactic acid (PLA) chains, followed by capping their extremities with ITA. The poly(lactate)-itaconate PLA-ITA was then used to formulate NPs. The degradation and drug release processes of the polymer conjugate NPs were studied qualitatively and quantitatively. The molecular structures of released species were characterized by using liquid NMR spectroscopy and mass spectrometry. We discovered a complex NP hydrolysis process forming diverse oligomers, as well as monomeric lactic acid (LA) and drug ITA. The slow degradation process led to a low release of free drugs, although raising the pH from 5.3 to 7.4 induced a slight increase in the amounts of released products. TEM images showed that bulk erosion is likely to play the primary role in the degradation of PLA-ITA NPs. The overall results and methodology can be of interest for understanding the mechanisms of NP degradation and drug release of this new polymer-drug conjugate system.https://www.mdpi.com/1422-0067/23/22/14461drug deliverypolymer nanoparticlespoly(lactic acid)itaconic acidNMR spectroscopy |
| spellingShingle | Mai Dang Le Vuong Mohamed Haouas Merve Seray Ural Didier Desmaële Charlotte Martineau-Corcos Ruxandra Gref Degradation of Polymer-Drug Conjugate Nanoparticles Based on Lactic and Itaconic Acid International Journal of Molecular Sciences drug delivery polymer nanoparticles poly(lactic acid) itaconic acid NMR spectroscopy |
| title | Degradation of Polymer-Drug Conjugate Nanoparticles Based on Lactic and Itaconic Acid |
| title_full | Degradation of Polymer-Drug Conjugate Nanoparticles Based on Lactic and Itaconic Acid |
| title_fullStr | Degradation of Polymer-Drug Conjugate Nanoparticles Based on Lactic and Itaconic Acid |
| title_full_unstemmed | Degradation of Polymer-Drug Conjugate Nanoparticles Based on Lactic and Itaconic Acid |
| title_short | Degradation of Polymer-Drug Conjugate Nanoparticles Based on Lactic and Itaconic Acid |
| title_sort | degradation of polymer drug conjugate nanoparticles based on lactic and itaconic acid |
| topic | drug delivery polymer nanoparticles poly(lactic acid) itaconic acid NMR spectroscopy |
| url | https://www.mdpi.com/1422-0067/23/22/14461 |
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