Alkyl Esters of L-Ascorbic Acid: From Synthesis to Applications

LUCIANO A. BENEDINI; MARIA LAURA FANANI; RAQUEL VIVIANA VICO

Ascorbic Acid: Properties, Synthesis and Applications

Nova Science Publishers

Lugar: Nwe York; Año: 2016; p. 156 - 182

Antioxidants are important additives in food, cosmetics and pharmaceutics, and vitamin C is one of the best-positioned for industrial applications. The usage of native L-ascorbic acid is limited to water-containing media because it is hydrophilic. To overcome this, an extensive effort has been made to develop new amphiphilic derivatives capable of being applied in lipophilic environments. The alkyl derivatives obtained through esterification of the primary hydroxyl group of L-ascorbic acid with carboxylic acids are the most widely studied compounds from the synthetic, physicochemical and pharmaceutical point of view, as well as being those most used in commercial formulations. This chapter offers a comprehensive review of the bibliography regarding the main pathways to synthesize these alkyl derivatives, involving enzyme catalysis and esterification in acidic or alkaline media to obtain the alkanoyl-6-O-ascorbic acid esters (ASCn). This information is presented together with their stability properties. Besides its antioxidant properties, the ASCn family has been used in different pharmacological preparations for its amphiphilic nature. The presence of the acyl chain provides the capacity to self-organize into micelles and coagels when suspended in water. Knowledge of the phase behavior of surfactants in aqueous media is important for understanding the properties of these systems and is vital for numerous industrial applications. These, along with a review of surface properties of the ASCn family, are dealt with in this chapter. ASCn amphiphiles, when self-organized at the air-water interface, form Gibbs and Langmuir monolayers with a large variety of stability, phase states and surface textures, depending on the length of the acyl chain moiety and ionization conditions. Furthermore, different members of the ASCn family have differences in their effectiveness for particular pharmaceutical purposes. Thus, the physicochemical properties of each member of this drug family may be determinant for their efficacy in pharmaceutical processes, in particular those related to surface phenomena and interaction with biomembranes. Cell membranes are the first contact of lipophilic drugs with cells and often form a reservoir. Drug/membrane interaction is thus a fundamental condition for their pharmacological function and a potential regulatory point. We review here some attempts to experimentally explore the interaction and the general physicochemical effect of ASCn family members when they are incorporated into model lipid membranes under controlled conditions.Finally, we review some approaches to the use of ASCn in biomedicine. Those are based mainly on I) their antioxidant capacity, because the presence of ASCn derivatives in formulations may prevent the degradation of drugs sensitive to light exposure, oxidant or reactive oxygen compounds, and/or II) the capacity of ASCn to form micelles, coagels and liquid crystals, which can modify some properties of the medium and act as drug delivery nanostructures. The new strategies in the use of ASCn comprise examples from liposome-based encapsulated nanoparticles to novel adjuvant activity of ASCn liquid crystals with high immunological efficiency.