title: The effect of novel surfactants and Solutol HS 15 on paclitaxel aqueous solubility and permeability across a Caco-2 monolayer.
abstract: The effect of novel surfactants on the aqueous solubility and the permeability of paclitaxel across a Caco-2 cell monolayer were examined in this work. The solubility and permeability of paclitaxel was evaluated in the presence of four soft surfactants (SS) KXN441, KXN424, KXN437, and KXN 337 and Solutol HS15. All surfactants increased the aqueous solubility of paclitaxel. Caco-2 cell membrane integrity in the presence of SS and Solutol HS15 was assessed by mannitol permeability and LDH release. All surfactants were tested at 0.5x CMC, 5x CMC and 1.5 mM concentrations. The effect of SSs on paclitaxel permeability was concentration dependent. At all concentrations tested, KXN 441 and Solutol HS 15 showed partially inhibition of drug efflux with no discernable change in mannitol permeability or cytotoxicity as observed with LDH release. At these concentrations, other SSs exhibited some partial efflux inhibition along with compromised membrane integrity and increasing mannitol permeability. In conclusion, all SSs were able to increase the aqueous solubility and permeability of paclitaxel across Caco-2 cells monolayer. However, KXN441 and Solutol HS15 were able to enhance paclitaxel permeability across Caco-2 monolayer without cytotoxicity.
authors.affiliation: School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
authors.forename: Adam W G
authors.initials: AW
authors.lastname: Alani
authors.forename: Deepa A
authors.initials: DA
authors.lastname: Rao
authors.forename: Ron
authors.initials: R
authors.lastname: Seidel
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Jim
authors.initials: J
authors.lastname: Jiao
authors.forename: Glen S
authors.initials: GS
authors.lastname: Kwon
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry*; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008027:Light; D008353:Mannitol / Q000737:chemistry; D008823:Micelles; D017239:Paclitaxel / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012542:Scattering, Radiation; D012995:Solubility; D013229:Stearic Acids / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D013229:Stearic Acids; D013501:Surface-Active Agents; D008353:Mannitol; D011092:Polyethylene Glycols; C067028:Solutol HS 15; D007770:L-Lactate Dehydrogenase; D017239:Paclitaxel