Chemical hydrolysis of DOTAP and DOPE in a liposomal environment.
In this study the hydrolysis kinetics of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and 1,2-dioleoyltrimethylammoniumpropane (DOTAP) in net neutral DPPC-DOPE (3:1, mol/mol) and cationic DOTAP-DOPE (1:1, mol/mol) liposomes are described. The log k(obs)-pH profile for DOTAP-DOPE liposomes differs markedly from earlier observed hydrolysis profiles: the slope approaches zero in the acidic region and +1 in the alkaline region. The concept of amine-influenced hydrolysis is introduced to explain the lack of pH dependency in the acidic region of the log k(obs)-pH profiles.
Vernooij
E A A M
EA
Department of Pharmaceutics, Faculty of Pharmacy, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80 082, 3508 TB, Utrecht, The Netherlands.
Kettenes-van den Bosch
J J
JJ
Underberg
W J M
WJ
Crommelin
D J A
DJ
D004337:Drug Carriers / Q000493:pharmacokinetics*; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism / Q000493:pharmacokinetics*; D005456:Fluorescent Dyes / Q000378:metabolism / Q000493:pharmacokinetics; D006868:Hydrolysis; D008081:Liposomes / Q000493:pharmacokinetics; D010714:Phosphatidylethanolamines / Q000378:metabolism / Q000493:pharmacokinetics*; D000644:Quaternary Ammonium Compounds / Q000378:metabolism / Q000493:pharmacokinetics*
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D004337:Drug Carriers; D005229:Fatty Acids, Monounsaturated; D005456:Fluorescent Dyes; D008081:Liposomes; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane