Rapamycin-Loaded, Capryol-TM 90 and Oleic Acid Mediated Nanoemulsions: Formulation Development, Characterization and Toxicity Assessment

This study was planned to explore the capability of nanoemulsions (nes) consisting of capryol-tm 90 and oleic acid for the delivery of rapamycin (rap). permeability and cytotoxicity of rap-loaded nes were also inspected. pseudo-ternary phase diagrams were created with oleic acid and capryol-tm 90 (as oil phase) and four surfactants and co-surfactants at various weight ratios (r_sm). selected nes from o/w region on the phase diagrams with the drug concentration of 1 mg/ml, were prepared via the spontaneous emulsification technique, characterized for particle size and subjected to stability tests at various temperatures over 9-12months. cumulative drug release was determined for a period of 48 h using a dialysis sac. the assay of rap was determined using hplc technique. cytotoxicity of nes was evaluated by mtt assay on breast cancer cell line, namely skbr-3. the permeability of rap-loaded nes across caco-2 mono layers was assessed by measurement of teer (transepithelial electrical resistance) value. the intracellular uptake of coumarin 6-loaded nes by skbr-3 cells was also investigated using florescence microscopy. nes containing oleic acid/tween 20/propyleneglycol, capryol-tm 90/tween 20/iso-propanol, and capryol-tm 90/cremophor® rh40/transcutol®p showed more cytotoxicity and permeability compared with the rap methanolic solution. the minimum toxic concentration of rap in ne formulations was found to be 7.5 µg/ml. the highest intracellular uptake was observed for the ne composed of capryol-tm 90/tween 20/isopropanol which was in consistent with the results obtained from cytotoxicity and permeability tests. the overall results implicated that this novel carrier was effective for enhancing rap permeation in caco-2 cell membrane along with enhancement of cytotoxicity.