Abstract
Objective: To investigate whether macrophages in the synovial lining can be selectively eliminated by local administration of an improved boron-10 (10B) containing liposome formulation combined with neutron irradiation (boron neutron capture synovectomy [BNCS]).
Methods: Disodium dodecahydrododecaborate (Na210B12H12) was encapsulated into unilamellar liposomes (10B-liposomes). 10B-liposomes were injected into the mouse knee joint. Amounts of 10B in synovial tissue were measured over time using inductively coupled plasma-optical emission spectrometry (ICP-OES). Arthritis was induced in knee joints of mice. Joint inflammation and cartilage destruction was measured using histology.
Results: When a 10 μl 10B-liposome solution (containing 40 μg 10B) was injected into the murine knee joint, high concentrations of 10B were measured in macrophages in the synovial lining (At 24 h 306±226 μg. g−1 macrophages). Completing the BNCS by neutron irradiation of the legs 24 h after 10B-liposome injection showed a clear selective depletion of macrophages in synovial lining of the knee joints. An estimated total physical dose of 13±9 Gy was given to the macrophages. When arthritis was induced in the macrophage-depleted joints, swelling of the knee was significantly lower as compared to the controls (53% and 79% lower at days 1 and 3, respectively). Histology confirmed the influx of inflammatory cells was strongly decreased and severe cartilage destruction was almost completely prevented.
Conclusion: BNCS using an improved 10B-containing liposome formulation can cause selective depletion of macrophages in the synovial lining of murine knee joints. As a result of this proof-of principle, future applications are recommended.