Polyethyleneglycol-stabilized manganese-substituted hydroxylapatite as a potential contrast agent for magnetic resonance imaging: particle stability in biologic fluids.
OBJECTIVE
Polymer-stabilized manganese(II)-substituted hydroxylapatite (MnHA) has been investigated as a particulate contrast agent for magnetic resonance imaging. The MnHA core requires a polymer coating to retard opsonization, thereby prolonging its systemic persistence. Therefore, the aim of this study was to assess the stability of various formulations in biologic media in vitro.


METHODS
Polyethyleneglycol-coated manganese(II)-substituted hydroxylapatite particles were studied in bovine plasma as a function of the concentration of polymer in the formulation. Particle sizing techniques and nuclear magnetic resonance proton relaxometry were used to evaluate both in vitro and in vivo stability.


RESULTS
A small-sized particle (approximately 10 nm 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 (approximately 100 nm diameter) were present along with the small-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.
Fallis
S
S
Imaging Division, Mallinckrodt, Inc., St. Louis, MO 63134, USA.
Beaty-Nosco
J
J
Dorshow
R B
RB
Adzamli
K
K
D000818:Animals; D001826:Body Fluids / Q000737:chemistry*; D002417:Cattle; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D017886:Durapatite / Q000097:blood / Q000737:chemistry*; D008027:Light; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008345:Manganese / Q000097:blood / Q000737:chemistry*; D010316:Particle Size; D010592:Pharmaceutic Aids / Q000737:chemistry* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D011817:Rabbits; D012542:Scattering, Radiation; D012996:Solutions; D013997:Time Factors
D003287:Contrast Media; D010592:Pharmaceutic Aids; D012996:Solutions; D011092:Polyethylene Glycols; D008345:Manganese; D017886:Durapatite