6533b823fe1ef96bd127e244

RESEARCH PRODUCT

Engineering approaches in siRNA delivery.

Sara CasconeRoberto Andrea AbbiatiMario GrassiMichela AbramiAnna Angela BarbaGianluca ChiarappaVincenzo La CarrubbaGabriele GrassiGiovanna TomaiuoloDiego CaccavoFrancesco Carfì PaviaDavide MancaGaetano LambertiGiulio GhersiValerio BrucatoStefano Guido

subject

0301 basic medicine3003siRNAs Delivery vectors in vitro models Mathematical modeling Physical modelingDelivery vectors; In vitro models; Mathematical modeling; Physical modeling; SiRNAs; 3003Pharmaceutical ScienceNanotechnology02 engineering and technologyComputational biologyBiology03 medical and health sciencesDrug Delivery SystemsHumanssiRNAs; Delivery vectors; in vitro models; Mathematical modeling; Physical modelingRNA Small Interferingin vitro modelsPhysical modelingSettore ING-IND/34 - Bioingegneria IndustrialeHydrogelsDelivery vectorsModels Theoretical021001 nanoscience & nanotechnologyDelivery vectorsiRNAsClinical PracticeHydrogel030104 developmental biologyin vitro modelsiRNAMathematical modeling0210 nano-technologyBlood streamDrug Delivery SystemClearanceHuman

description

siRNAs are very potent drug molecules, able to silence genes involved in pathologies development. siRNAs have virtually an unlimited therapeutic potential, particularly for the treatment of inflammatory diseases. However, their use in clinical practice is limited because of their unfavorable properties to interact and not to degrade in physiological environments. In particular they are large macromolecules, negatively charged, which undergo rapid degradation by plasmatic enzymes, are subject to fast renal clearance/hepatic sequestration, and can hardly cross cellular membranes. These aspects seriously impair siRNAs as therapeutics. As in all the other fields of science, siRNAs management can be advantaged by physical-mathematical descriptions (modeling) in order to clarify the involved phenomena from the preparative step of dosage systems to the description of drug-body interactions, which allows improving the design of delivery systems/processes/therapies. This review analyzes a few mathematical modeling approaches currently adopted to describe the siRNAs delivery, the main procedures in siRNAs vectors’ production processes and siRNAs vectors’ release from hydrogels, and the modeling of pharmacokinetics of siRNAs vectors. Furthermore, the use of physical models to study the siRNAs vectors’ fate in blood stream and in the tissues is presented. The general view depicts a framework maybe not yet usable in therapeutics, but with promising possibilities for forthcoming applications.

10.1016/j.ijpharm.2017.02.032https://pubmed.ncbi.nlm.nih.gov/28213276