1. Silk fibroin nanoparticles for locoregional cancer therapy: Preliminary biodistribution in a murine model and microfluidic GMP-like production.
- Author
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Ferrera F, Resaz R, Bari E, Fenoglio D, Mastracci L, Miletto I, Modena A, Perteghella S, Sorlini M, Segale L, Filaci G, Torre ML, and Giovannelli L
- Abstract
Silk fibroin nanoparticles (SFNs) have been widely investigated for drug delivery, but their clinical application still faces technical (large-scale and GMP-compliant manufacturing), economic (cost-effectiveness in comparison to other polymer-based nanoparticles), and biological (biodistribution assessments) challenges. To address biodistribution challenge, we provide a straightforward desolvation method (in acetone) to produce homogeneous SFNs incorporating increasing amounts of Fe
2 O3 (SFNs-Fe), detectable by Magnetic Resonance Imaging (MRI), and loaded with curcumin as a model lipophilic drug. SFNs-Fe were characterized by a homogeneous distribution of the combined materials and showed an actual Fe2 O3 loading close to the theoretical one. The amount of Fe2 O3 incorporated affected the physical-chemical properties of SFNs-Fe, such as polymer matrix compactness, mean diameter and drug release mechanism. All formulations were cytocompatible; curcumin encapsulation mitigated its cytotoxicity, and iron oxide incorporation did not impact cell metabolic activity but affected cellular uptake in vitro. SFNs-Fe proved optimal for biodistribution studies, as MRI showed significant nanoparticle retention at the administration site, supporting their potential for locoregional cancer therapy. Finally, technical and economic challenges in SFN production were overcome using a GMP-compliant microfluidic scalable technology, which optimized preparation to produce smaller particle sizes compared to manual methods and reduced acetone usage, thus offering environmental and economic benefits. Moreover, enabling large-scale production of GMP-like SFNs, this represents a considerable step forward for their application in the clinic., Competing Interests: Declaration of competing interest Sara Perteghellaa and Maria Luisa Torre are co-founders and members of the company's advisory board Pharmaexceed S.r.l. Marzio Sorlini is the CEO of Pharmaexceed S.r.l. This company had no role in the design of the study, in the collection, analysis, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2024
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