Long-chain cationic gemini surfactants as drug retention adjuvant on liposomes. A methodological approach with atorvastatin

Abstract

This study delves into the development and characterization of dipalmitoyl phosphatidylcholine (DPPC) liposomes incorporated with gemini surfactant (tetradecamethylene-1,14 bis(dimethyl tetradecyl ammonium bromide); 14-14-14) and atorvastatin, aimed at enhancing drug delivery efficiency for cardiovascular diseases. The integration of gemini surfactants into liposomes is investigated for its potential to improve atorvastatin encapsulation and retention, addressing the drug's poor water solubility and the limitations of conventional liposomal systems. Through a combination of dynamic light scattering (DLS), differential scanning calorimetry (DSC), and molecular dynamics (MD) simulations, the study reveals that the presence of gemini surfactants significantly reduces liposome size and polydispersity, indicative of a more uniform and potentially unilamellar structure. DSC analysis highlights a decrease in transition temperatures and an alteration in transition symmetry, suggesting enhanced stability and a favourable drug release profile at physiological temperatures. MD simulations provide insight into the internalization mechanism of gemini surfactants and atorvastatin within the liposomal bilayer, demonstrating their mutual incorporation facilitated by polar interactions. Spectrophotometry-based retention studies further confirmed that liposomes containing gemini surfactants exhibit superior atorvastatin retention capabilities, nearly doubling the encapsulation efficiency compared to conventional liposomes. This research highlights the promising role of gemini surfactant-incorporated liposomes as an efficient drug delivery platform for cardiovascular therapeutics, offering insights into the molecular interactions and structural dynamics underlying their enhanced performance.