Radiolanthanide-loaded agglomerated Fe3O4 nanoparticles for possible use in the treatment of arthritis: formulation, characterization and evaluation in rats.

Sudipta Chakraborty,Rajesh Kumar Vatsa,Raghumani Singh Ningthoujam,A Rajeswari,Ashutosh Dash,K V Vimalnath,K S Sharma,Usha Pandey,H D Sarma,Jagannath Jagannath

doi:10.1039/c5tb00677e

Sudipta Chakraborty, Rajesh Kumar Vatsa + Show 8 more

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https://doi.org/10.1039/c5tb00677e

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Abstract

This investigation reports the preparation of agglomerated Fe3O4 nanoparticles and evaluation of its utility as a viable carrier in the preparation of radiolanthanides as potential therapeutic agents for the treatment of arthritis. The material was synthesized by a chemical route and characterized by XRD, FT-IR, SEM, EDX and TEM analysis. The surface of agglomerated particle possessed ion pairs (-O-:Na+) after dispersing particles in a NaHCO3 solution at pH = 7 which is conducive for radiolanthanide (*Ln = 90Y, 153Sm, 166Ho, 169Er, 177Lu) loading by replacement of Na+ ions with tripositive radiolanthanide ions. Radiolanthanide-loaded particulates exhibited excellent in vitro stability up to ∼3 half-lives of the respective lanthanide radionuclides when stored in normal saline at 37 °C. The radiochemical purities of the loaded particulates were found to be retained to the extent of >70% after 48 h of storage when challenged by a strong chelator DTPA present at a concentration as high as 5 mM, indicating fairly strong chemical association of lanthanides with agglomerated Fe3O4 nanoparticles. Biodistribution studies of 90Y and 166Ho-loaded particulates carried out after intra-articular injection into one of the knee joints of a normal Wistar rat revealed near-complete retention of the radioactive preparations (>98% of the administered radioactivity) within the joint cavity even after 72 h post injection. This was further confirmed by sequential whole-body radio-luminescence imaging. These experimental results are indicative of the potential use of radiolanthanide-loaded agglomerated Fe3O4 nanoparticles for the treatment of arthritis.

Highlights

While a myriad of factors contribute to the utility of radiation synovectomy (RSV), selection of an appropriate bÀ emitting radionuclide of optimum tissue penetration range along with desirable radioactive decay PaperJournal of Materials Chemistry B Radionuclide166Ho 165Dy 153Sm 177Lu 175Yb 169Er Half-life26.9 h 2.35 h 46.9 h 6.65 d 4.18 d 9.39 d Eb(max) (MeV)Max. tissue penetration
We describe the synthesis, and radiochemical and physicochemical characterization of agglomerated Fe3O4 nanoparticles (Agl-MNP) loaded with lanthanide radionuclides namely 90Y, 166Ho, 153Sm, 177Lu and 169 Er for their possible utilization in the treatment of arthritis of different joints of the human body
The objective of development of a synthetic protocol based on a simple co-precipitation method that led to the formation of agglomerated Fe3O4 nanoparticles, with a size distribution (1–10 mm) optimal for use in RSV, has been successfully achieved

Summary

Introduction

While a myriad of factors contribute to the utility of RSV, selection of an appropriate bÀ emitting radionuclide of optimum tissue penetration range along with desirable radioactive decay. The radiochemical purity of the radiolabeled preparation was determined using the same technique subsequent to the removal of unlabeled *Ln activity by washing of loaded Agl-MNP using normal saline. The radio-luminescence imaging ( known as Cerenkov luminescence imaging) technique is based on the emission of visible light during the passage of particulate radiation from the decay of certain radionuclides thorough the condensed phase (that of biological tissue in the present case).[39] For biodistribution studies, loaded particles (B2 MBq) suspended in 100 mL of normal saline were injected intra-articularly into one of the knee joints of each animal. The results of the bio-distribution studies carried out in normal Wistar rats after loco-regional administration of 90Y- and 166Holoaded Agl-MNPs into one of the knee joint cavities of the animals are summarized in Tables 4 and 5, respectively. Values in the parentheses represent standard deviation.At every time point 4 animals have been used. 166Ho-Fe3O4 preparation was injected into the synovial cavity of the arthritis affected knee joints of each animal. a No detectable radioactivity above background. b Excretion has been calculated by subtracting the activity accounted in all the organs from the total activity injected

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