Researchers at University of Napoli Federico II, Berlin Institute of Health, Ludwig-Maximilians-Universität München, University of Campania Luigi Vanvitelli, University of Milano, and University of British Columbia used PLGA-Rhodamine B (cat# AV011 https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AV011#h) from PolySciTech : Akina, Inc. (www.PolySciTech.com) combined with ionizable lipids to form nanoparticles for siRNA delivery through inhaled formulations. This research holds promise to improve respiratory therapy. Read more: Brusco, Susy, Ersilia Villano, Teresa Silvestri, Amar J. Azad, Muge Molbay, Ivana d'Angelo, Agnese Miro et al. "Lipid@ polymer hybrid nanoparticles for efficient siRNA transport across the lung barriers: Mechanistic insights into the role of Ionizable lipids." Journal of Colloid and Interface Science (2026): 140683. https://www.sciencedirect.com/science/article/pii/S002197972600860X
“Building on growing evidence that ionizable lipids improve RNA delivery, in this work, we developed ionizable lipid/poly(lactic-co-glycolic acid) hybrid nanoparticles (iLipid@PLGA hNPs), consisting in a PLGA core modified at surface with either 1,2-dioleoyloxy-3-dimethylaminopropane (DODMA), 1,2-dioleoyl-3-trimethylammonium-propane (DODAP), or the branched-tail proprietary amino lipid ALC0315. iLipid@PLGA hNPs were engineered to meet key requirements for inhalation. Thorough physicochemical characterization revealed how the choice of ionizable lipid influences pH responsiveness, surface composition, and architecture of iLipid@PLGA hNPs. In vitro studies demonstrated effective siRNA encapsulation, adjustable release kinetics, and poor interactions with mucus components, as assessed by combined UV–Vis, Dynamic Light Scattering, and Small Angle X-ray Scattering analyses. Confocal microscopy analysis of A549 cells transfected with iLipid@PLGA hNPs showed reduced colocalization of AlexaFluor647-labeled siRNA with lysosomes over time, suggesting enhanced endosomal escape in the case of DODMA@PLGA hNPs. Functional validation using GAPDH-targeting siRNA (siGAPDH) confirmed cellular uptake and gene silencing in normal human bronchial epithelial (NHBEs) cells, confirming the superior performance of DODMA@PLGA hNPs. Finally, representative fluorescently labeled DODMA@PLGA hNPs successfully diffused across a 3D air–liquid interface (ALI) cell model, simulating the human bronchial epithelial barrier. These findings highlight the successful integration of ionizable lipids into polymeric nanoparticles, establishing iLipid@PLGA hNPs as versatile and efficient carriers for siRNA therapeutics. This breakthrough supports their continued development in respiratory nanomedicine and in the local treatment of lung diseases.”
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