Synthesis and characterization of long chain O-acyl-l-alaninols and investigation of drug encapsulation and release by equimolar O-myristoyl-l-alaninol/SDS catanionic liposomes†

Abstract

L-Alaninol and its derivatives display interesting biological and pharmacological properties, suggesting potential use in biomedical applications. Here we present the synthesis and characterization of O-acyl-L-alaninols (OAAOHs) bearing long, saturated acyl chains (n = 14–20). Our study focuses on examining their thermotropic phase behavior, supramolecular organization, and interaction with sodium dodecyl sulfate (SDS), with the objective of preparing novel catanionic liposomes. Results from differential scanning calorimetry and powder X-ray diffraction (PXRD) studies revealed an odd–even alternation in the transition enthalpies (ΔH_t), transition entropies (ΔS_t) and d-spacings of OAAOHs. A linear dependence was observed in the values of ΔH_t and ΔS_t on the acyl chain length, independently for even and odd acyl chains for the dry samples (solid–liquid phase transition), wherein the odd chain length molecules exhibited higher values than the even chain length series. Analysis of crystal structures of O-palmitoyl-L-alaninol and O-heptadecanoyl-L-alaninol showed a tilted bilayer structure organised in a head-to-head (and tail-to-tail) fashion, although the packing arrangement within the bilayer was different for the odd- and even chain length compounds. However, significant similarities were also observed in the intermolecular interactions, with both compounds being stabilized by a number of C–H⋯O and N–H⋯Cl hydrogen bonds. Exploration of the interaction between O-myristoyl-L-alaninol and SDS revealed the formation of an equimolar catanionic complex, which assembles in aqueous dispersion to yield liposomes of 220–260 nm diameter. The vesicles could encapsulate doxorubicin, a widely used anticancer drug, and showed higher release at acidic pH (<7.0), indicating their potential utility as drug carriers in cancer chemotherapy.