Silk Fibroin Nanoparticles: A Biocompatible Multi-Functional Polymer for Drug Delivery

Abstract

The versatility of nanomedicines allows for various modifications of material type, size, charge and functionalization, offering a promising platform for biomedical applications including tumor targeting. One such material, silk fibroin (SF) has emerged, displaying an excellent combination of mechanical and biological properties characterized by its high tensile and breaking strength, elongation, stiffness and ductility. High stability allows SF to maintain its chemical structure even at high temperatures (around 250°C) and compared with other biological polymers like polylactide (PLA), poly(lactic-co-glycolic acid) (PLGA), and collagen, SF shows excellent biocompatibility and lower immunogenic response making it a very suitable material for drug delivery and tissue engineering. Here we describe the structure, synthesis and properties of SF nanoparticles. We evaluate its emergence as a multi-functional polymer for its utility as a nanocarrier to deliver cancer therapies directly to tumors together with considerations for its clinical use.

Translational Challenges and Prospective Solutions in the Implementation of Biomimetic Delivery Systems

“…BDSs have emerged as a transformative frontier in nanomedicine, promising unparalleled advantages in drug delivery and therapeutic modalities. These systems, rooted in the principles of self-assembly, molecular recognition, and biocompatibility, encompass a variety of platforms such as liposomes [91], PNPs [30,74,162,242,341,342], extracellular vesicles [17], and polysaccharides [300]. Their clinical applications have been praised for achievements in targeted delivery, reduced side effects, and improved therapeutic outcomes.…”

“…Silk fibroin (SF) and gelatin (GA) have been extensively researched for their potential in biomimetic delivery systems, owing to their biocompatibility and adjustable degradation rates, essential for in vivo nanoparticle application, especially in drug delivery [72][73][74]162]. However, translational challenges arise from their inherent complexity and the associated reproducibility issues in nanoparticle fabrication.…”

“…NDs, in their design, carry lipidbased structures, which render them susceptible to oxidation or hydrolysis, challenges further exacerbated by potential size inconsistencies that can lead to variable biodistribution, affecting their therapeutic reach and efficacy [150]. Finally, the naturally-derived PNPs, fibroin and gelatin, introduce their own set of challenges: their natural sourcing can lead to variability in nanoparticle properties between batches, potential toxicity stemming from the use of chemical crosslinkers, and the concern of rapid degradation in physiological settings, which can obstruct the controlled, sustained release of therapeutic agents [162,167,173,319]. In summation, while the promise of PNPs in revolutionizing therapeutic delivery is undeniable, their path is fraught with multifaceted scientific challenges that mandate rigorous research and optimization before clinical fruition.…”

Translational Challenges and Prospective Solutions in the Implementation of Biomimetic Delivery Systems

“…Silk fibroin (SF) and gelatin (GA) have been extensively researched for their potential in biomimetic delivery systems, owing to their biocompatibility and adjustable degradation rates, essential for in vivo nanoparticle application, especially in drug delivery [120][121][122][123]. However, translational challenges arise from their inherent complexity and the associated reproducibility issues in nanoparticle fabrication.…”

“…NDs, in their design, carry lipid-based structures, which render them susceptible to oxidation or hydrolysis, challenges further exacerbated by potential size inconsistencies that can lead to variable biodistribution, affecting their therapeutic reach and efficacy [108]. Finally, the naturally-derived PNPs, Fibroin and Gelatin, introduce their own set of challenges: their natural sourcing can lead to variability in nanoparticle properties between batches, potential toxicity stemming from the use of chemical crosslinkers, and the concern of rapid degradation in physiological settings, which can obstruct the controlled, sustained release of therapeutic agents [120,128,134,286]. In summation, while the promise of PNPs in revolutionizing therapeutic delivery is undeniable, their path is fraught with multifaceted scientific challenges that mandate rigorous research and optimization before clinical fruition.…”