POLYETHYLENEGLYCOL-STABILIZED MANGANESE-SUBSTITUTED HYDROXYLAPATITE AS A POTENTIAL CONTRAST AGENT FOR MAGNETIC-RESONANCE-IMAGING - PARTICLESTABILITY IN BIOLOGIC FLUIDS
S. Fallis et al., POLYETHYLENEGLYCOL-STABILIZED MANGANESE-SUBSTITUTED HYDROXYLAPATITE AS A POTENTIAL CONTRAST AGENT FOR MAGNETIC-RESONANCE-IMAGING - PARTICLESTABILITY IN BIOLOGIC FLUIDS, Investigative radiology, 33(12), 1998, pp. 847-852
RATIONALE AND OBJECTIVES. Polymer-stabilized manganese(II)-substituted
hydroxylapatite (MnHA) has been investigated as a particulate contras
t agent for magnetic resonance imaging. The MnHA core requires a polym
er coating to retard opsonization, thereby prolonging its systemic per
sistence. Therefore, the aim of this study was to assess the stability
of various formulations in biologic media in vitro. METHODS. Polyethy
leneglycol-coated manganese(II)-substituted hydroxylapatite particles
were studied in bovine plasma as a function of the concentration of po
lymer in the formulation, Particle sizing techniques and nuclear magne
tic resonance proton relaxometry were used to evaluate both in vitro a
nd in vivo stability. RESULTS. A small-sized particle (similar to 10 n
m diameter) that is stable in bovine plasma and rabbit whole blood was
formed in formulations with high amounts of polymer concentration. In
formulations with low amounts of polymer concentration, larger-sized
particles (similar to 100 nm diameter) were present along with the sma
ll-sized population. The larger particles de-aggregated into the small
-size particle distribution on dispersion in bovine plasma and rabbit
whole blood. CONCLUSIONS. Ultrasmall particles with high surface coat
were stable in plasma, whereas larger aggregates de-aggregated. Unlike
Mn2+, the interaction of polyethyleneglycol-stabilized manganese(II)-
substituted hydroxylapatite with plasma proteins was weak.