Fallis S, Beaty-Nosco J, Dorshow R B, Adzamli K
Imaging Division, Mallinckrodt, Inc., St. Louis, MO 63134, USA.
Invest Radiol. 1998 Dec;33(12):847-52. doi: 10.1097/00004424-199812000-00001.
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.
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.
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.
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.
聚合物稳定的锰（II）取代羟基磷灰石（MnHA）已被研究用作磁共振成像的颗粒造影剂。MnHA核心需要聚合物涂层来延缓调理作用，从而延长其在体内的存留时间。因此，本研究的目的是评估各种制剂在体外生物介质中的稳定性。
研究了聚乙二醇包被的锰（II）取代羟基磷灰石颗粒在牛血浆中的情况，该颗粒是制剂中聚合物浓度的函数。采用颗粒大小测定技术和核磁共振质子弛豫测量法来评估体外和体内稳定性。
在聚合物浓度高的制剂中形成了一种在牛血浆和兔全血中稳定的小尺寸颗粒（直径约10 nm）。在聚合物浓度低的制剂中，除了小尺寸颗粒群体外，还存在较大尺寸的颗粒（直径约100 nm）。较大的颗粒在分散于牛血浆和兔全血中时会解聚为小尺寸颗粒分布。
具有高表面涂层的超小颗粒在血浆中稳定，而较大的聚集体会解聚。与Mn2+不同，聚乙二醇稳定的锰（II）取代羟基磷灰石与血浆蛋白的相互作用较弱。
