Novel high relaxivity colloidal particles based on the specific phase organisation of amphiphilic gadolinium chelates with cholesterol.
To obtain high T(1)-relaxivity colloidal particles with a simultaneously high loading of amphiphilic Gd-chelates, a novel drug dosage form based on the phase organisation of amphiphilic gadolinium chelates with cholesterol was developed. In order to find a formulation, which exhibit both high T(1)-relaxivity and gives small particles a D-optimal mixture design (experimental design) was applied. Gadolinium 1,4,7-tris(carboxymethyl)-10-(2-hydroxyhexadecyl)-1,4,7,10-tetraazacyclododecane (Gd-HHD-DO3A) and cholesterol at approximately equimolar ratio proved to form thermodynamic stable disc-like colloidal particles as seen by cryo-electron micrographs. T(1)-relaxivity of these particles was typically around 20mM(-1)s(-1) and the size below 100 nm (photon correlation spectroscopy (PCS)). The particles do most probably not interact with blood components as no change in T(1)-relaxivity was observed when the particles were mixed with whole blood. The particles were stable at room temperature for at least 6 months.
Gløgård
Christian
C
Department of Medicinal Chemistry, School of Pharmacy, University of Oslo, PO Box 1155 Blindern, N-0318, Oslo, Norway. christian.glogard@farmasi.uio.no
Stensrud
Gry
G
Klaveness
Jo
J
D002784:Cholesterol / Q000737:chemistry*; D003102:Colloids; D003287:Contrast Media / Q000737:chemistry*; D020285:Cryoelectron Microscopy; D004355:Drug Stability; D004356:Drug Storage; D005682:Gadolinium; D006573:Heterocyclic Compounds, 1-Ring / Q000097:blood / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D009942:Organometallic Compounds / Q000097:blood / Q000737:chemistry*; D009994:Osmolar Concentration; D019308:Palmitic Acid; D010316:Particle Size; D013696:Temperature
D003102:Colloids; D003287:Contrast Media; D006573:Heterocyclic Compounds, 1-Ring; D009942:Organometallic Compounds; C477443:gadolinium 1,4,7-tris(carboxymethyl)-10-(2-hydroxyhexadecyl)-1,4,7,10-tetraazacyclododecane; D019308:Palmitic Acid; D002784:Cholesterol; D005682:Gadolinium