Morel S, Terreno E, Ugazio E, Aime S, Gasco M R
Dipartimento di Scienza e Tecnologia del Farmaco, Torino, Italy.
Eur J Pharm Biopharm. 1998 Mar;45(2):157-63. doi: 10.1016/s0939-6411(97)00107-0.
This work deals with the preparation and relaxometric investigations of solid lipid nanoparticles (SLN) containing [Gd-DTPA(H2O)]2- and [Gd-DOTA(H2O)]-. These paramagnetic chelates are commonly used as contrast agents (CA) for magnetic resonance imaging (MRI) owing to their ability to strongly increase the tissue water proton relaxation rate. The amount of gadolinium(III) (Gd(III)) complex included in the SLN has been evaluated and, on this basis, it has been found that the longitudinal relaxivity of these Gd(III) chelates apparently does not vary, at physiological pH, following their inclusion in SLN. We are unable to establish whether this is due to the free exchange of water from the inner compartment containing the Gd(III) chelate to the bulk water or whether the observed relaxation rate is essentially determined by a fraction of the complex which is close to the surface of the SLN in a region easily accessible to the bulk water. At acidic pH values, the relaxivity of the paramagnetic SLN containing the less thermodynamically and kinetically stable [Gd-DTPA(H2O)]2- markedly increases. This effect may be ascribed to an increased immobilization and/or to an enhanced hydration of the complex on SLN.
本工作涉及含[Gd-DTPA(H₂O)]²⁻和[Gd-DOTA(H₂O)]⁻的固体脂质纳米粒(SLN)的制备及弛豫特性研究。这些顺磁性螯合物由于能够显著提高组织水质子弛豫率,常被用作磁共振成像(MRI)的造影剂(CA)。已对SLN中钆(III)(Gd(III))配合物的含量进行了评估,在此基础上发现,在生理pH值下,这些Gd(III)螯合物包封于SLN后,其纵向弛豫率显然没有变化。我们无法确定这是由于含有Gd(III)螯合物的内隔室中的水与大量水自由交换所致,还是观察到的弛豫率主要由在大量水易于接近的区域中靠近SLN表面的一部分配合物所决定。在酸性pH值下,含有热力学和动力学稳定性较差的[Gd-DTPA(H₂O)]²⁻的顺磁性SLN的弛豫率显著增加。这种效应可能归因于配合物在SLN上固定化增加和/或水合作用增强。