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Development of siRNA and Budesonide Dual-Loaded Hybrid Lipid-Polymer Nanoparticles by Microfluidics Technology as a Platform for Dual Drug Delivery to Macrophages: An In Vitro Mechanistic Study.

Articolo
Data di Pubblicazione:
2023
Abstract:
Macrophages play a key role in the development of many diseases, like tissue injury, cancer, and autoimmune diseases. So far, single-drug loaded nanoparticles are developed to target macrophages. Nevertheless, macrophage dysregulation can induce multiple conditions, i.e., inflammation and fibrosis. Therefore, the simultaneous codelivery of a small molecule drug and a small interfering RNA (siRNA) for gene silencing may be beneficial to modulate macrophage dysfunction. Herein, hybrid lipid–polymer nanoparticles (LPNs) coloaded with both budesonide and enhanced green fluorescence protein siRNA (eGFP-siRNA) as model anti-inflammatory small molecule drug and siRNA, respectively, are developed by an optimized microfluidics method. Specifically, a poly(lactic-co-glycolic acid) core is coated by a lipid shell, and LPNs with size homogeneity and colloidal stability are obtained. Both payloads are loaded efficiently, and a controlled release is achieved. Additionally, LPNs are nontoxic in murine RAW 264.7 cells and human THP-1 cells and are efficiently taken up by these cells. Finally, the transfection efficiency of dual-loaded LPNs is high at low LPNs doses, thus proving the suitability of this nanosystem for gene silencing. Overall, the optimized LPNs are a suitable nanoplatform for the dual drug delivery to macrophages for the treatment of complex conditions requiring dual therapeutic approaches.
Tipologia CRIS:
1.1 Articolo in rivista
Elenco autori:
Cerda, Sl; Fontana, F; Wang, Sq; Correia, A; Molinaro, G; Tello, Rp; Hirvonen, J; Celia, C; Barreto, G; Santos, Ha.
Autori di Ateneo:
CELIA Christian
Link alla scheda completa:
https://ricerca.unich.it/handle/11564/821756
Pubblicato in:
ADVANCED THERAPEUTICS
Journal
Progetto:
Innovation, digitalisation and sustainability for the diffused economy in Central Italy - VITALITY
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