The synthesis of MP-CDCA conjugates and dissolution kinetics of model cholesterol gallstones.

ABSTRACT

The comb-like copolymers of polycarboxylic acid were synthesized and then reacted with chenodeoxycholic acid (CDCA) to obtain a series of conjugates, MPn-CDCA, where n is the number of the groups of oxyethylene in each graft chain. This was confirmed by infrared spectroscopy and thin-layer chromatography. We investigated the effects of dissolving model cholesterol gallstones with the MPn-CDCA conjugates in phosphate-buffered saline at pH 7.4. The dissolution rates of CDCA, MP40-CDCA, MP30-CDCA, MP20-CDCA and MP10-CDCA were 5.33, 5.717, 17.59, 6.868 and 9.615x10(-7)kgm(-2)s(-1), micellar solubilities were 0.2431, 3.095, 12.972, 5.248 and 5.790kgm(-3) and total resistances were 5.33, 5.717, 17.59, 6.868 and 9.615x10(-7)kgm(-2)s(-1), respectively. These studies suggested that the interfacial resistance was the dominant rate-determining factor in dissolving model cholesterol gallstones. Model cholesterol gallstones could be more effectively dissolved by increasing the steric interactive potential energy of side chains and ensuring that the hydrophilic-lipophilic properties of MP-CDCA are within an appropriate range. The micellar dissolution rates of model cholesterol gallstones by MP20-CDCA were significantly faster than by the other conjugates.