Mucoadhesive Silk Fibroin Nanoparticles for Drug Delivery to the Ocular Surface

<b><i>Purpose:</i></b> To develop silk fibroin nanoparticles (SFNs) for prolonged drug delivery to the ocular surface. <b><i>Methods:</i></b> SFNs were prepared using nanoprecipitation, coated with chitosan (CS; positively charged), and stabilized with polyethylene glycol 400. Their morphology, particle size distribution, and surface charge were analyzed using dynamic light scattering. Fourier transform infrared (FTIR) spectroscopy assessed the intermolecular interactions between CS and silk fibroin. The entrapment efficiencies (EE) for sodium fluorescein (NaF) and Nile Red (NR), which served as hydrophilic and hydrophobic drug surrogates, respectively, were determined. The mucoadhesiveness of SFNs was examined <i>ex vivo</i> with freshly isolated porcine eyes. Cellular uptake and cytotoxicity were evaluated in a human corneal epithelium cell line (HCEC). <b><i>Results:</i></b> SFNs were spherical, measuring 198.47 ± 35.54 nm in diameter, and had a surface charge of 38.33 ± 0.67 mV. The coating of CS on SFNs resulted in a peak shift in the amide group in the FTIR spectrum. The maximum EEs for NaF and NR in SFNs were approximately 95% and 67%, respectively. SFNs exhibited prolonged mucoadhesion on corneas for over 240 min and were rapidly endocytosed by HCEC in less than 30 min without inducing cytotoxicity. <b><i>Conclusion:</i></b> The properties of SFNs are suitable for delivering drugs to the ocular surface.