Physicochemical and toxicological properties of novel amino acid-based amphiphiles and their spontaneously formed catanionic vesicles

Abstract

a b s t r a c tThe 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.

Self-assembling systems: Mining a rich vein

“…The synthesis and examination of new self-assembling compounds have drawn international attention, as illustrated here via an incomplete and arbitrary listing: Argentina (amphiphilic cyclodextrins) [1]; Australia (amphiphilic dendrimers) [2]; Brazil (sugar-based surfactants) [3]; Canada (amphiphilic copolymers) [4]; China (chiral surfactants) [5]; France (noncovalent amphiphiles) [6]; Germany (bolaamphiphiles) [7]; India (multiple-headgroup surfactants) [8]; Italy (gemini surfactants) [9]; Iran (cleavable surfactants) [10]; Japan (p-electronic amphiphiles) [11]; Korea (T-shaped amphiphiles) [12]; The Netherlands (carbohydrate-based gemini surfactants) [13]; Portugal (amino acid-based amphiphiles) [14]; Spain (urea-based surfactants) [15]; Sweden (heterogemini surfactants) [16]; United Kingdom (light-sensitive surfactants) [17]; and United States (redox-active surfactants) [18].…”

Exploring the usefulness of key green physicochemical properties: Quantitative structure–activity relationship for solvents from biomass

“…The aggregation behavior of chemicals has been used in other studies for a better understanding of their toxic effect [25]. The aggregation behavior of chemicals has been used in other studies for a better understanding of their toxic effect [25].…”

“…The critical aggregation concentration (i.e., the concentration at which small concentrations of molecular aggregates appear) provides useful information about bioavailability. The aggregation behavior of chemicals has been used in other studies for a better understanding of their toxic effect [25]. When the molecules are not aggregated, an increase in the bioavailability of molecules in the environment is expected [26].…”

Survival, mobility, and membrane‐bound enzyme activities of freshwater planarian, Dugesia japonica, exposed to synthetic and natural surfactants

“…For example, DTAB, a cationic surfactant, was harmful to D. japonica, with a 48-h LC50 of 126.79 mg/L, but it was found to be very toxic to Daphnia magna with a 48-h LC50 of 0.25 mg/L [17]. Both natural and synthetic surfactants can be toxic to planarians.…”