Molecules, Vol. 24, Pages 3751: Characterization of Redox-Responsive LXR-Activating Nanoparticle Formulations in Primary Mouse Macrophages

Molecules, Vol. 24, Pages 3751: Characterization of Redox-Responsive LXR-Activating Nanoparticle Formulations in Primary Mouse Macrophages Molecules doi: 10.3390/molecules24203751 Authors: Tyler K. T. Smith Zaina Kahiel Nicholas D. LeBlond Peyman Ghorbani Eliya Farah Refel Al-Awosi Marceline Cote Suresh Gadde Morgan D. Fullerton Activation of the transcription factor liver X receptor (LXR) has beneficial effects on macrophage lipid metabolism and inflammation, making it a potential candidate for therapeutic targeting in cardiometabolic disease. While small molecule delivery via nanomedicine has promising applications for a number of chronic diseases, questions remain as to how nanoparticle formulation might be tailored to suit different tissue microenvironments and aid in drug delivery. In the current study, we aimed to compare the in vitro drug delivering capability of three nanoparticle (NP) formulations encapsulating the LXR activator, GW-3965. We observed little difference in the base characteristics of standard PLGA-PEG NP when compared to two redox-active polymeric NP formulations, which we called redox-responsive (RR)1 and RR2. Moreover, we also observed similar uptake of these NP into primary mouse macrophages. We used the transcript and protein expression of the cholesterol efflux protein and LXR target ATP-binding cassette A1 (ABCA1) as a readout of GW-3956-induced LXR activation. Following an initial acute uptake period that was meant to mim...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research