Evaluation of cell tolerability of a series of lipoamino acids using biological membranes and a biomembrane model.
The interaction of a series of amphiphilic 2-alkyl aminoacids (lipoamino acids, LAAs) with different cell cultures and biomembrane models was investigated. LAAs can be useful promoieties to modify the physico-chemical properties of many drugs, and in particular their lipophilicity. Tests were performed in vitro on mammalian cells (murine astrocytes) and human red blood cells (haemolysis), and in vivo on rabbit eye as alternative models to assess the tolerability or the potential damaging effects of these compounds on different biological systems. The mode of interaction of LAAs with pure phospholipid multilamellar liposomes, taken as a biomembrane model, was also analysed by differential scanning calorimetry experiments. Different tolerability/toxicity patterns were obtained in the various models; in particular, the most lipophilic terms of the series, methyl 2-aminohexadecanoate (LAA16), displayed haemolytic activity and toxicity for mouse astrocyte cultures. A specific assay confirmed that LAA16 acted at level of cell membranes, while neither any damaging effects on nucleus or apoptotic induction were observed. The shorter-chain LAAs and the tetradecyl homologue (LAA14) showed the best compatibility with the various cell models.
Pignatello
R
R
Department of Pharmaceutical Sciences, University of Catania, Catania, Italy. r.pignatello@unict.it
Noce
C
C
Campisi
A
A
Acquaviva
R
R
Bucolo
C
C
Puglisi
G
G
Toth
I
I
D000596:Amino Acids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002152:Calorimetry, Differential Scanning; D002462:Cell Membrane / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D005123:Eye / Q000187:drug effects / Q000473:pathology; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology*; D008081:Liposomes; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D051379:Mice; D019814:Myristic Acid; D019308:Palmitic Acid; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry / Q000494:pharmacology*
D000596:Amino Acids; D008055:Lipids; D008081:Liposomes; D017382:Reactive Oxygen Species; D013501:Surface-Active Agents; D019814:Myristic Acid; D019308:Palmitic Acid; D004134:Dimyristoylphosphatidylcholine