Chemical hydrolysis of DOTAP and DOPE in a liposomal environment. |
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Authors: | E A A M Vernooij J J Kettenes-van den Bosch W J M Underberg D J A Crommelin |
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Affiliation: | Department of Pharmaceutics, Faculty of Pharmacy, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80 082, 3508 TB, Utrecht, The Netherlands. |
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Abstract: | 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. |
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