Smart Inhalation Therapy: Boosting siRNA Efficacy with Inulin-Based Multifunctional Polymers
Salvatore E. Drago, Marta Cabibbo, Cinzia Scialabba, Emanuela F. Craparo, Gennara Cavallaro
TL;DR
This paper introduces a new inulin-based polymer that improves siRNA delivery to the lungs, helping treat respiratory diseases more effectively.
Contribution
The study presents a novel inulin-based copolymer for efficient siRNA delivery via inhalation, overcoming lung barriers.
Findings
The polymer forms stable siRNA complexes with a size below 30 nm and shows pH-dependent membrane destabilization.
Polyplexes remain stable in mucus and surfactant, with high muco-diffusivity and over 80% cell viability in biocompatibility tests.
siRNA-mediated gene silencing was demonstrated in MDA-MB-231-eGFP cells, showing therapeutic potential for respiratory diseases.
Abstract
Therapeutic delivery of siRNA via inhalation holds significant promise for managing severe pulmonary diseases. However, an effective delivery platform capable of overcoming the lung’s physical and biological barriers is essential to achieve efficient gene silencing in the airway epithelium. Here, we describe the synthesis of an inulin (INU)-based copolymer, INU-VS-g-(PMeOx; bAPAE), designed for siRNA inhalation. A stepwise synthesis was employed: first, INU was functionalized with divinyl sulfone to form INU-VS, allowing controlled conjugation of 1,2-bis(3-aminopropylamino)ethane (bAPAE) and poly(2-methyl-2-oxazoline) (PMeOx) at, respectively, 25 and 5 mol % on the total INU repeat units. The resulting copolymer exhibited protonatable amine groups essential for nucleic acid complexation. Stable formation of siRNA polyplexes was found at low polymer/siRNA weight ratios (R = 5), with a…
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Taxonomy
TopicsRNA Interference and Gene Delivery · Inhalation and Respiratory Drug Delivery · Advanced Drug Delivery Systems