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Fluorescent DTPA-Silk Fibroin Nanoparticles Radiolabeled with <sup>111</sup> In: A Dual Tool for Biodistribution and Stability Studies
摘要： This work aims to provide an effective and novel dual tool for the biodistribution studies of biopolimeric nanoparticles by using modified silk fibroin nanoparticles as a model. This is an indispensable step in the evaluation of the applicability of biopolymeric nanoparticles as drug delivery systems. In this paper, we report a new facile method for radiolabeling silk fibroin nanoparticles conjugated to the chelating agent diethylenetriamine pentaacetic acid (DTPA) and tagged with fluorescein isothiocyanate (FITC). Nanoparticles were characterized by means of dynamic light scattering (DLS), scanning electron microscopy (SEM), infrared and fluorescence spectroscopy. The in vitro studies included the stability in biological media and the evaluation of the cytotoxicity of the nanoparticles in a cell culture. The in vivo study was focused in the scintigraphic study over 24 h conducted on New Zealand rabbits, after intra-articular injection of [111In]In-nanoparticles containing 8.03 ± 0.42 MBq. Biodistribution of the nanoparticles was assessed also ex vivo by fluorescence microscopy of post mortem biopsied organs. This radiolabeling method was reproducible and robust with high radiolabeling efficiency (~80 %) and high specific activity suitable for the in vivo studies. Radiolabeled nanoparticles, having hydrodynamic radius of 113.2 ± 2.3 nm, a polydispersity index (PdI) of 0.101 ± 0.015 and Z-potential of -30.1 ± 2.0 mV, showed and optimum retention in the articular space, without activity clearance up to 24 h post injection. Thus, an easy and robust radiolabeling method has been developed, and its applicability is demonstrated in vitro and in vivo studies, showing its value for future investigation of silk fibroin nanoparticles as versatile and stable (steady) local drug delivery systems for consideration as a therapeutic option, particularly in the treatment of joint disorders.
关键词： biodistribution,theragnostic,radiolabeling,mesenchymal stem cells culture,FITC,silk fibroin nanoparticles,Indium-111,stability
更新于2025-09-23 15:19:57
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Silk fibroin nanoparticles for enhanced bio-macromolecule delivery to the retina
摘要： The aim of this study was to investigate intravitreal injection of silk fibroin nanoparticles (SFNs) encapsulating bio-macromolecules, achieving enhanced drug bioavailability and extended retention in retina. SFNs were prepared with regenerated silk fibroin (RSF) using desolvation method with fluorescein isothiocyanate labeled bovine serum albumin (FITC-BSA) as bio-macromolecular model drug encapsulated. In vitro physicochemical properties and in vitro drug release of FITC-BSA loaded SFNs (FITC-BSA-SFNs) were evaluated. Cytotoxicity, cellular uptake, and retention of FITC-BSA-SFNs were determined in human retinal pigment epithelial cell line (ARPE-19). In addition, in vivo distribution and safety of intravitreally administered FITC-BSA-SFNs were investigated in New Zealand white rabbits. The particle size of FITC-BSA-SFNs was 179.1±3.7 nm with polydispersity index (PDI) of 0.102±0.033 and the zeta potential was greater than -25 mV. FITC-BSA-SFNs exhibited excellent biocompatibility with no cytotoxicity observed within 24 h and 48 h in AREP-19 cells. Compared to FITC-BSA solution, FITC-BSA-SFNs showed enhanced cellular uptake and prolonged retention. Furthermore, FITC-BSA-SFNs achieved accumulated distribution and extended retention in retina in vivo following intravitreal injection compared to a single administration of free drug solution. Therefore, this bio-macromolecule delivery platform based on SFNs could have great potential in the treatment of posterior segment disorders.
关键词： bio-macromolecules,Silk fibroin nanoparticles,ocular drug delivery,posterior segment diseases,intravitreal injection
更新于2025-09-10 09:29:36