PLA-amine from PolySciTech used in development of atherosclerosis-targeted nanoparticles for treatment of heart disease

Heart disease, typically due to atherosclerotic lesions, is one of the leading causes of death in USA. Most treatments for this disease focus on surgical interventions (e.g. stent placement), which is often utilized in acute situations, or on systemic medicines such as statins, which are typically applied as a preventative. There is a need for therapies to be applied in non-emergency situations but where atherosclerotic lesions are known to be present. Conventionally, nanoparticles have been applied for use against cancer, however they can be targeted to lesions by using appropriate targeting moieties. Recently, researchers working jointly at Harvard Medical School, New York University, Technical University of Denmark, Korea Institute of Ceramic Engineering and Technology, Korea Advanced Institute of Science and Technology, and King Abdulaziz University used PLA-NH2 (PolyVivo AI041, from PolySciTech as a reactive precursor for generating a fluorescently-conjugated tracer as part of a novel nanoparticle-based system for treatment of artherosclerosis. Read more: Yu, Mikyung, Jaume Amengual, Arjun Menon, Nazila Kamaly, Felix Zhou, Xiaoding Xu, Phei Er Saw et al. “Targeted Nanotherapeutics Encapsulating Liver X Receptor Agonist GW3965 Enhance Antiatherogenic Effects without Adverse Effects on Hepatic Lipid Metabolism in Ldlr−/− Mice.” Advanced Healthcare Materials (2017).

“Abstract: The pharmacological manipulation of liver X receptors (LXRs) has been an attractive therapeutic strategy for atherosclerosis treatment as they control reverse cholesterol transport and inflammatory response. This study presents the development and efficacy of nanoparticles (NPs) incorporating the synthetic LXR agonist GW3965 (GW) in targeting atherosclerotic lesions. Collagen IV (Col IV) targeting ligands are employed to functionalize the NPs to improve targeting to the atherosclerotic plaque, and formulation parameters such as the length of the polyethylene glycol (PEG) coating molecules are systematically optimized. In vitro studies indicate that the GW-encapsulated NPs upregulate the LXR target genes and downregulate proinflammatory mediator in macrophages. The Col IV-targeted NPs encapsulating GW (Col IV–GW–NPs) successfully reaches atherosclerotic lesions when administered for 5 weeks to mice with preexisting lesions, substantially reducing macrophage content (≈30%) compared to the PBS group, which is with greater efficacy versus nontargeting NPs encapsulating GW (GW–NPs) (≈18%). In addition, mice administered the Col IV–GW–NPs do not demonstrate increased hepatic lipid biosynthesis or hyperlipidemia during the treatment period, unlike mice injected with the free GW. These findings suggest a new form of LXR-based therapeutics capable of enhanced delivery of the LXR agonist to atherosclerotic lesions without altering hepatic lipid metabolism.”

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