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Propaedeutic study for the delivery of nucleic acid-based molecules from PLGA microparticles and stearic acid nanoparticles

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Authors: G Grassi, N Coceani, R Farra, B Dapas, G Racchi, et al

Published Date May 2006 Volume 2006:1(4) Pages 523 - 533
DOI: http://dx.doi.org/10.2147/IJN.S

G Grassi1,2, N Coceani3, R Farra1, B Dapas1, G Racchi2, N Fiotti1, A Pascotto4, B Rehimers4, G Guarnieri1, M Grassi5

1Department of Internal Medicine, University Hospital of Trieste, italy; 2Department of Molecular Pathology, University Hospital of Tübingen, Tübingen, Germany; 3Department of Biochemistry, Biophysics and Macromolecular Chemistry, University of Trieste, italy; 4Cardiovascular Department, Civic Hospital, Venezia, Italy; 5Department of Chemical Engineering, DICAMP, University of Trieste, Italy

Abstract: We studied the mechanism governing the delivery of nucleic acid-based drugs (NABD) from microparticles and nanoparticles in zero shear conditions, a situation occurring in applications such as in situ delivery to organ parenchyma. The delivery of a NABD molecule from poly(DL-lactide-co-glycolide) (PLGA) microparticles and stearic acid (SA) nanoparticles was studied using an experimental apparatus comprising a donor chamber separated from the receiver chamber by a synthetic membrane. A possible toxic effect on cell biology, as evaluated by studying cell proliferation, was also conducted for just PLGA microparticles. A mathematical model based on the hypothesis that NABD release from particles is due to particle erosion was used to interpret experimental release data. Despite zero shear conditions imposed in the donor chamber, particle erosion was the leading mechanism for NABD release from both PLGA microparticles and SA nanoparticles. PLGA microparticle erosion speed is one order of magnitude higher than that of competing SA nanoparticles. Finally, no deleterious effects of PLGA microparticles on cell proliferation were detected. Thus, the data here reported can help optimize the delivery systems aimed at release of NABD from micro- and nanoparticles.

Keywords: nucleic acids delivery, microparticle, nanoparticle, erosion, modeling








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