A novel biocompatible bicephalous dianionic surfactant from oleic acid for solid lipid nanoparticles

New biocompatible bicephalous dianionic surfactant with low CMC value was successfully synthesized and its efficacy in pharmaceutical drug delivery system was explored by preparing solid lipid nanoparticles (SLNs) of ketoconazole, a BCS class II drug. Oleic acid based dianionic surfactant was synthesized by attachment of oleic acid through ester linkage, to a bidentate head component, prepared by 1,4-addition of propanolamine and tert-butyl acrylate, followed by hydrolysis and neutralization with sodium bicarbonate. Its critical micelle concentration (CMC), hydrophilic–lipophilic balance and log Poctanol/water were found to be 1.6 mM/L, 34.68 and −2.96, respectively. Cytotoxicity study, conducted using sulforhodamine B assay, showed LC50, GI50 and TGI values > 80 μg/ml indicating its biocompatibility. It was found to be non-irritant by in vivo skin irritation study. The particle size, polydispersity index, and zeta potential of the optimized formulation were 98.2 ± 1.74 nm, 0.462 ± 0.016, and −49.6 mV, respectively. Further, the SLNs were characterized by scanning electron microscopy, differential scanning calorimetry and X-ray diffraction studies. Drug entrapment efficiency was found to be 87.42 ± 0.31%, and the SLNs exhibited good stability over a period of 3 months. The current investigations, therefore, report the successful development of systematically optimized SLNs of ketoconazole.

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► Synthesis of new oleic acid based bicephalous dianionic surfactant.
► Finding of CMC less than half of sodium oleate was an important observation.
► In vitro cytotoxicity and in vivo skin irritation study revealed safe nature of surfactant for use in drug delivery systems.
► Application in formulation development of solid lipid nanoparticles of ketoconazole, a BCS class II drug.