Effect of phospholipid composition on characterization of liposomes containing 9-nitrocamptothecin.
9-Nitrocamptothecin (9-NC), a newly developed camptothecin derivative, had poor solubility in any pharmaceutically acceptable solvents. One way of improving the solubility is to formulate the drug into liposomes. However, 9-NC has low affinity to lipid membranes resulting in a very low drug-to-liposome entrapment. We developed a novel liposome-based 9-NC formulation which was composed of soybean phosphatidylcholine (SPC), hydrogenated soybean phosphatidylcholine (HSPC), and cholesterol. Compared with conventional liposomes composed of only SPC and cholesterol, 9-NC/lipid molar ratio increased from 1:72 to 1:18 while incorporation efficiency was still maintained about 80%. In addition, after 9-NC was encapsulated into novel liposomes, pharmacokinetic results revealed an increase in area under the plasma concentration-time curve (AUC) and a decrease in distribution volume of 9-NC following intravenous administration to rats. Increased stability in plasma may account for the improved pharmacokinetic behavior of the novel liposomes. Effect of HSPC/SPC molar ratio on characterization of the novel liposomes was also investigated. Except for drug/lipid molar ratio and encapsulation efficiency, HSPC/SPC molar ratio had only a little effect on other properties of novel liposomes. In conclusion, the study suggests that the novel liposomes can act as promising carriers for hydrophobic substances such as 9-NC.
Chen
J
J
Department of Pharmaceutics, China Pharmaceutical University, Nanjing, P. R. China.
Ping
Q N
QN
Guo
J X
JX
Chu
X Z
XZ
Song
M M
MM
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D002784:Cholesterol / Q000737:chemistry; D004339:Drug Compounding; D005240:Feasibility Studies; D006865:Hydrogenation; D007275:Injections, Intravenous; D008081:Liposomes; D008297:Male; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013025:Glycine max / Q000737:chemistry
D000970:Antineoplastic Agents; D008081:Liposomes; D010713:Phosphatidylcholines; D002784:Cholesterol; C079905:rubitecan; D002166:Camptothecin