The synthesis of MP-CDCA conjugates and dissolution kinetics of model cholesterol gallstones.
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.
Gong
Rui-yu
RY
Pharmaceutical School of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Lü
Zhi-liang
ZL
Zhang
Li-dong
LD
Du
Li-ping
LP
Zhang
Da
D
Qiao
Xue-liang
XL
Li
Jian-rong
JR
D001826:Body Fluids / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry* / Q000627:therapeutic use; D002635:Chenodeoxycholic Acid / Q000737:chemistry* / Q000627:therapeutic use; D002784:Cholesterol / Q000737:chemistry*; D004058:Diffusion; D004353:Drug Evaluation, Preclinical; D042882:Gallstones / Q000737:chemistry* / Q000188:drug therapy; D006801:Humans; D007700:Kinetics
D002264:Carboxylic Acids; D002635:Chenodeoxycholic Acid; D002784:Cholesterol