Physicochemical and toxicological properties of novel amino acid-based amphiphiles and their spontaneously formed catanionic vesicles.
The design of efficient liposomal systems for drug delivery is of considerable biomedical interest. In this context, vesicles prepared from cationic/anionic surfactants may offer several advantages, mainly due to their spontaneity in formation and long-term stability. There is also an impending need to produce less toxic, more biocompatible amphiphiles, while maintaining the desirable aggregation properties. In this work, we present data for acute toxicity to Daphnia magna (IC(50)), and potential ocular irritation (HC(50)) for some newly prepared ionic surfactants with dodecyl chains, derived from the amino acids tyrosine (Tyr), serine (Ser), hydroxyproline (Hyp) and lysine (Lys). The micellization behavior of the compounds, evaluated from surface tension measurements, is presented and compared to more conventional ionic amphiphiles. Two types of spontaneouly formed catanionic vesicles, composed either by a dodecyltrimethylammonium bromide (DTAB)/Lys-derivative and or Ser-/Lys-derivative mixture, have also been tested for their ecotoxicity and hemolytic potential. All the micelle-forming surfactants as well as the vesicle-containing mixtures are found to have lower ecotoxicity than the reference surfactant DTAB. Moreover, the results from hemolysis and hemoglobin denaturation tests show that the Tyr- and Lys-derivatives are moderately irritant, whereas the Hyp- and Ser- ones are just slightly irritant. Even more significantly, the vesicle-containing mixtures exhibit lower hemolytic activity than the neat surfactants, a positive result for their potential use in liposomal formulations.
Brito
Rodrigo O
RO
Departmento de Química, Faculdade de Ciências, Centro de Investigação em Química, Universidade do Porto, Porto, Portugal.
Marques
Eduardo F
EF
Silva
Sandra G
SG
do Vale
Maria Luísa
ML
Gomes
Paula
P
Araújo
Maria J
MJ
Rodriguez-Borges
J Enrique
JE
Infante
Maria Rosa
MR
Garcia
Maria Teresa
MT
Ribosa
Isabel
I
Vinardell
María Pilar
MP
Mitjans
Montserrat
M
D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D000838:Anions; D002412:Cations; D055598:Chemical Phenomena / Q000187:drug effects*; D003621:Daphnia / Q000187:drug effects; D005123:Eye / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007509:Irritants / Q000633:toxicity; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D013500:Surface Tension / Q000187:drug effects; D013501:Surface-Active Agents / Q000737:chemistry / Q000633:toxicity*; D023382:Toxicity Tests, Acute
D000596:Amino Acids; D000838:Anions; D002412:Cations; D007509:Irritants; D008823:Micelles; D013501:Surface-Active Agents