title: Engineering approaches in siRNA delivery.
abstract: 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.
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Salerno, Via Giovanni Paolo II, 132, 84084, Fisciano (SA), Italy.
authors.forename: Anna Angela
authors.initials: AA
authors.lastname: Barba
authors.affiliation: Dipartimento di Ingegneria Industriale, Università degli Studi di Salerno, Via Giovanni Paolo II, 132, 84084, Fisciano (SA), Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Cascone
authors.affiliation: Dipartimento di Ingegneria Industriale, Università degli Studi di Salerno, Via Giovanni Paolo II, 132, 84084, Fisciano (SA), Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Caccavo
authors.affiliation: Dipartimento di Ingegneria Industriale, Università degli Studi di Salerno, Via Giovanni Paolo II, 132, 84084, Fisciano (SA), Italy. Electronic address: glamberti@unisa.it.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Lamberti
authors.affiliation: Department of Engineering and Architecture, University of Trieste, Via Alfonso Valerio, 6/A, I-34127 Trieste, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Chiarappa
authors.affiliation: Department of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, I-34149 Trieste, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Abrami
authors.affiliation: Department of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, I-34149 Trieste, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Grassi
authors.affiliation: Department of Engineering and Architecture, University of Trieste, Via Alfonso Valerio, 6/A, I-34127 Trieste, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Grassi
authors.affiliation: Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale, Università di Napoli Federico II, Italy; CEINGE Biotecnologie avanzate, Napoli, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tomaiuolo
authors.affiliation: Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale, Università di Napoli Federico II, Italy; CEINGE Biotecnologie avanzate, Napoli, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Guido
authors.affiliation: Università degli Studi di Palermo, DICAM - Dipartimento di Ingegneria Civile, Ambientale, Aerospaziale, dei Materiali and ATeN Center - CHAB, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Brucato
authors.affiliation: Università degli Studi di Palermo, DICAM - Dipartimento di Ingegneria Civile, Ambientale, Aerospaziale, dei Materiali and ATeN Center - CHAB, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Carfì Pavia
authors.affiliation: Università degli Studi di Palermo, STEBICEF - Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche and ATeN Center - CHAB, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Ghersi
authors.affiliation: Università degli Studi di Palermo, DICAM - Dipartimento di Ingegneria Civile, Ambientale, Aerospaziale, dei Materiali and ATeN Center - CHAB, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: La Carrubba
authors.affiliation: PSE-Lab, Process Systems Engineering Laboratory - Dipartimento di Chimica, Materiali e Ingegneria Chimica "Giulio Natta" Politecnico di Milano - Piazza Leonardo da Vinci 32, 20133 Milano, Italy.
authors.forename: Roberto Andrea
authors.initials: RA
authors.lastname: Abbiati
authors.affiliation: PSE-Lab, Process Systems Engineering Laboratory - Dipartimento di Chimica, Materiali e Ingegneria Chimica "Giulio Natta" Politecnico di Milano - Piazza Leonardo da Vinci 32, 20133 Milano, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Manca
mesh_terms: D016503:Drug Delivery Systems; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D008962:Models, Theoretical; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D020100:Hydrogels; D034741:RNA, Small Interfering
keywords: Delivery vectors; Mathematical modeling; Physical modeling; in vitro models; siRNAs