Design and comprehensive characterization of dry powder inhalation aerosols of simvastatin DPPC/DPPG lung surfactant-mimic nanoparticles/microparticles for pulmonary nanomedicine.
Autor: | Encinas-Basurto D; Skaggs Pharmaceutical Sciences Center, College of Pharmacy, The University of Arizona AZ USA.; Biopolymers-CTAOA, Research Center for Food and Development (CIAD, A.C.) Hermosillo Mexico., Acosta MF; Skaggs Pharmaceutical Sciences Center, College of Pharmacy, The University of Arizona AZ USA., Eedara BB; Skaggs Pharmaceutical Sciences Center, College of Pharmacy, The University of Arizona AZ USA.; Center for Translational Science, Florida International University 11350 SW Village Parkway Port St. Lucie FL 34987-2352 USA hmansour@fiu.edu +7(772) 345-4731., Fineman JR; Department of Pediatrics, University of California San Francisco School of Medicine San Francisco CA USA., Black SM; Center for Translational Science, Florida International University 11350 SW Village Parkway Port St. Lucie FL 34987-2352 USA hmansour@fiu.edu +7(772) 345-4731.; Department of Medicine, Division of Translational and Regenerative Medicine, The University of Arizona College of Medicine Tucson AZ USA., Mansour HM; Skaggs Pharmaceutical Sciences Center, College of Pharmacy, The University of Arizona AZ USA.; Center for Translational Science, Florida International University 11350 SW Village Parkway Port St. Lucie FL 34987-2352 USA hmansour@fiu.edu +7(772) 345-4731.; Department of Medicine, Division of Translational and Regenerative Medicine, The University of Arizona College of Medicine Tucson AZ USA.; The University of Arizona, BIO5 Institute Tucson AZ USA. |
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Jazyk: | angličtina |
Zdroj: | RSC advances [RSC Adv] 2024 Sep 16; Vol. 14 (40), pp. 29413-29427. Date of Electronic Publication: 2024 Sep 16 (Print Publication: 2024). |
DOI: | 10.1039/d4ra04947k |
Abstrakt: | The Rho Kinase (ROCK) pathway is recognized to be involved in changes that lead to remodeling in pulmonary hypertension (PH), particularly cellular processes including signaling, contraction, migration, proliferation, differentiation, and apoptosis. Simvastatin (Sim) has a potent anti-proliferative and pro-apoptotic effect on vasculature smooth muscle cells through the inhibition of the synthesis of isoprenoids intermediates which are essential for the post-translational isoprenylation of Rho, Rac, and Ras family GTPases. Sim targets the underlying mechanism in vascular remodeling. Using bionanomaterials and particle engineering design, this innovative study reports on the advanced inhalable dry powders composed of sim with synthetic phospholipid bionanomaterials, DPPC/DPPG, as a lung surfactant-mimic. These were successfully designed and produced as co-spray dried (Co-SD) nanoparticles and microparticles for nanomedicine delivery as dry powder inhalers (DPIs). Different techniques were used to comprehensively characterize the physicochemical properties of the resulting Co-SD particles. The Next Generation ImpactorTM (NGI™) was used with three different FDA-approved human DPI devices with varying shear stress which were the HandiHaler®, Neohaler®, Aerolizer® DPI devices for aerosol dispersion performance. The formulation-device interactions were examined and correlated. Using human lung cells from different lung regions, in vitro cell viability and transepithelial electrical resistance (TEER) at the air-liquid interface showed biocompatibility of the formulations as a function of dose. Competing Interests: The authors declare no conflict of interest. (This journal is © The Royal Society of Chemistry.) |
Databáze: | MEDLINE |
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