Selectively induced death of macrophages in the synovial lining of murine knee joints using ¹⁰B-liposomes and boron neutron capture synovectomy

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.

Keywords:

• arthritis
• synovial lining
• macrophages
• BNCS
• joint inflammation
• liposomes