| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 600233 | Colloids and Surfaces B: Biointerfaces | 2013 | 8 Pages |
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.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► 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.
