Radiolanthanide-loaded agglomerated Fe₃O₄nanoparticles for possible use in the treatment of arthritis: formulation, characterization and evaluation in rats

Abstract

This investigation reports the preparation of agglomerated Fe 3 O 4 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 À :Na + ) after dispersing particles in a NaHCO 3 solution at pH = 7 which is conducive for radiolanthanide (*Ln = 90 Y, 153 Sm, 166 Ho, 169 Er, 177 Lu) loading by replacement of Na + ions with tripositive radiolanthanide ions. Radiolanthanide-loaded particulates exhibited excellent in vitro stability up to B3 half-lives of the respective lanthanide radionuclides when stored in normal saline at 37 1C. The radiochemical purities of the loaded particulates were found to be retained to the extent of 470% 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 Fe 3 O 4 nanoparticles. Biodistribution studies of 90 Y and 166 Ho-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 (498% 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 Fe 3 O 4 nanoparticles for the treatment of arthritis.

Barium titanate microparticles as potential carrier platform for lanthanide radionuclides for their use in the treatment of arthritis

“…[1][2][3][4][5][6] The key determinants for the success of RSV are the selection of an appropriate radionuclide and a biocompatible carrier platform which results in robust and irreversible binding with the radionuclide. 4,[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] This is attributed to the availability of a package of therapeutically useful radionuclides among lanthanide elements having a wide range of energy (0.34-2.28 MeV) of β − emission along with other desirable decay characteristics. 2,3,7-9 As for example, radionuclide emitting β − having maximum energy more than 1.5 MeV would be suitable for knee and hip joints, while medium energy β − emitters (maximum energy 0.5-1.0 MeV) would be suitable for ankle, elbow, and wrist joints and low energy β − emitters (maximum energy less than 0.5 MeV) for finger joints.…”

“…2,3,7-9 As for example, radionuclide emitting β − having maximum energy more than 1.5 MeV would be suitable for knee and hip joints, while medium energy β − emitters (maximum energy 0.5-1.0 MeV) would be suitable for ankle, elbow, and wrist joints and low energy β − emitters (maximum energy less than 0.5 MeV) for finger joints. 7,10,11,15,19,20 In the present work, our aim was to put forward an innovative and effective carrier platform on which lanthanide ions can be easily loaded and the loaded particles of appropriate size could be used to deliver cytotoxic dose to the diseased synovium after loco-regional administration. Based on these considerations, a plethora of therapeutic radionuclides have been proposed and clinically utilized in RSV, among which radionuclide of lanthanide elements such as 90 Y (yttrium is considered as a pseudolanthanide), 153 Sm, 165 Dy, 166 Ho, 169 Er, and 177 Lu (Table 1) are prominent ones.…”

“…Based on these considerations, a plethora of therapeutic radionuclides have been proposed and clinically utilized in RSV, among which radionuclide of lanthanide elements such as 90 Y (yttrium is considered as a pseudolanthanide), 153 Sm, 165 Dy, 166 Ho, 169 Er, and 177 Lu ( Table 1) are prominent ones. 4,[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] This is attributed to the availability of a package of therapeutically useful radionuclides among lanthanide elements having a wide range of energy (0.34-2.28 MeV) of β − emission along with other desirable decay characteristics. Treatment of the chronic inflammatory disease affecting different joints of human body (viz.…”

“…Additionally, all these radionuclide can be produced in required quantity and adequate radionuclidic purity in a nuclear reactor with moderate thermal neutron flux. 7,10,11,15,19,20 In the present work, our aim was to put forward an innovative and effective carrier platform on which lanthanide ions can be easily loaded and the loaded particles of appropriate size could be used to deliver cytotoxic dose to the diseased synovium after loco-regional administration. This single carrier platform would result in a series of radiolanthanide-loaded particulates which can be used for different joints of human body based on the energy of β − emission of the radionuclide ( 166 Ho for knee and hip, 153 Sm for ankle and elbow, 177 Lu for elbow and wrist, 169 Er for finger).…”

“…Target for the production of 177 Lu from enriched Lu 2 O 3 (84.0% in176 Lu) powder was prepared as per our earlier reported procedure 10,27. The sealed ampoule was placed inside standard aluminum container, sealed, and irradiated in DHRUVA research reactor at Bhabha Atomic Research Centre, India, at a thermal neutron flux of~1.6 × 10 14 n.cm −2 .s −1 .…”