Nano-sized metal–organic frameworks (nanoMOFs), with engineered surfaces to enhance the targeting of the drug delivery, have proven efficient as drug nanocarriers.
Metal-organic framework nanoparticles (nanoMOFs) are novel porous drug delivery systems whose features include high drug loading capacity, versatile functionalization, biocompatibility, and biodegradability. However, little knowledge about the nature of nanoMOFs degradation mechanism is one of many reasons that prevents their clinical use. MIL-100 (MIL stands for Matériaux de l'Institut Lavoisier) is among the most studied nanoMOF for drug delivery.Here, we investigate at the atomic scale the degradation mechanism of metal(III)-trimesate nanoMIL-100 drug carrier in biological-mimicking phosphate medium. By using solid-state NMR (ssNMR) spectroscopy, we found that the first step of nanoMIL-100(Al) degradation is the substitution of labile water ligands, resulting in new coordination bonds between Al(III) and phosphate ions, followed by the substitution of trimesate ligands leading to their release. The data indicated that the reaction-limiting step most likely is the formation of an inorganic aluminophosphate layer at the nanoparticle surface and that drug encapsulation and surface coating affect the nanoMIL-100(Al) degradation. X-ray Absorption Near Edge Structure (XANES) spectroscopy study of nanoMIL-100(Fe) degradation corroborates the hypothesized alteration mechanism of nanoMIL-100(Al). From the ensemble of data, a stepwise degradation mechanism representative for the nanoMIL-100 drug delivery system is proposed.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.