TY - JOUR
T1 - Engineering approaches in siRNA delivery
AU - La Carrubba, Vincenzo
AU - Brucato, Valerio Maria Bartolo
AU - Carfi' Pavia, Francesco
AU - Ghersi, Giulio
AU - Tomaiuolo, Giovanna
AU - Cascone, Sara
AU - Guido, Stefano
AU - Abrami, Michela
AU - Grassi, Mario
AU - Caccavo, Diego
AU - Abbiati, Roberto Andrea
AU - Chiarappa, Gianluca
AU - Barba, Anna Angela
AU - Guido, Stefano
AU - Manca, Davide
AU - Lamberti, Gaetano
AU - Grassi, Gabriele
PY - 2017
Y1 - 2017
N2 - 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 vectorsâ production processes and siRNAs vectorsâ release from hydrogels, and the modeling of pharmacokinetics of siRNAs vectors. Furthermore, the use of physical models to study the siRNAs vectorsâ 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.
AB - 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 vectorsâ production processes and siRNAs vectorsâ release from hydrogels, and the modeling of pharmacokinetics of siRNAs vectors. Furthermore, the use of physical models to study the siRNAs vectorsâ 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.
KW - 3003
KW - Delivery vectors
KW - Mathematical modeling
KW - Physical modeling
KW - in vitro models
KW - siRNAs
KW - 3003
KW - Delivery vectors
KW - Mathematical modeling
KW - Physical modeling
KW - in vitro models
KW - siRNAs
UR - http://hdl.handle.net/10447/241989
M3 - Article
VL - 525
SP - 343
EP - 358
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
ER -