title: A novel biocompatible bicephalous dianionic surfactant from oleic acid for solid lipid nanoparticles.
abstract: 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 logPoctanol/water were found to be 1.6mM/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.
authors: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga (E), Mumbai 400019, India.
authors: Rahul S
authors: RS
authors: Kalhapure
authors: Krishnacharya G
authors: KG
authors: Akamanchi
mesh_terms: D000818:Animals; D000838:Anions / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D049109:Cell Proliferation / Q000187:drug effects*; D016503:Drug Delivery Systems; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007654:Ketoconazole / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008422:Materials Testing; D008823:Micelles; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry*; D019301:Oleic Acid / Q000737:chemistry*; D011817:Rabbits; D012867:Skin / Q000187:drug effects*; D017550:Spectroscopy, Fourier Transform Infrared; D013501:Surface-Active Agents / Q000737:chemistry / Q000494:pharmacology*; D014961:X-Ray Diffraction
chemical_list: D000838:Anions; D008055:Lipids; D008823:Micelles; D013501:Surface-Active Agents; D019301:Oleic Acid; D007654:Ketoconazole