Degradation of Polymer-Drug Conjugate Nanoparticles Based on Lactic and Itaconic Acid.

Autor: Vuong MDL; CNRS, Institut Lavoisier de Versailles, UVSQ, Université Paris-Saclay, 78000 Versailles, France.; CNRS, Institut des Sciences Moléculaires d'Orsay, Université Paris-Saclay, 91405 Orsay, France., Haouas M; CNRS, Institut Lavoisier de Versailles, UVSQ, Université Paris-Saclay, 78000 Versailles, France., Ural MS; CNRS, Institut des Sciences Moléculaires d'Orsay, Université Paris-Saclay, 91405 Orsay, France., Desmaële D; CNRS, Institut Galien Paris-Saclay, Université Paris-Saclay, 91400 Orsay, France., Martineau-Corcos C; CNRS, Institut Lavoisier de Versailles, UVSQ, Université Paris-Saclay, 78000 Versailles, France., Gref R; CNRS, Institut des Sciences Moléculaires d'Orsay, Université Paris-Saclay, 91405 Orsay, France.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2022 Nov 21; Vol. 23 (22). Date of Electronic Publication: 2022 Nov 21.
DOI: 10.3390/ijms232214461
Abstrakt: 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.
Databáze: MEDLINE
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