Towards optimised drug delivery: structure and composition of testosterone enanthate in sodium dodecyl sulfate monolayers

Abstract

Surface tension and specular neutron reflectivity measurements have been used, for the first time to systematically study both the interfacial structure and composition of monolayers of the soluble surfactant, sodium dodecyl sulfate containing a low-dose, poorly water soluble drug, testosterone enanthate. Modelling of the specular neutron reflectivity data suggests that the hydrophobic testosterone enanthate was adsorbed in the C12 hydrophobic tail region of the surfactant monolayer, regardless of the concentration of surfactant at the interface and whether or not additional drug was added to the interface. The location of the hydrophobic drug in the tail region of the surfactant monolayer is supported by the results of classical, large-scale molecular dynamics simulations. The thickness of the surfactant monolayer obtained, in the presence and absence of drug, using molecular dynamics simulations was in good agreement with the corresponding values obtained from the specular neutron reflectivity measurements. The stoichiometry of surfactant:drug at the air-water interface at sodium dodecyl sulfate concentrations above the critical micelle concentration was determined from specular neutron reflectivity measurements to be approximately 3 : 1, and remained constant after the spreading of further testosterone enanthate at the interface. Significantly, this stoichiometry was the same as that obtained in the micelles from bulk solubilisation studies. Important insights into the preferred location of drug in surfactant monolayers at the air-water interface as well as its effect on the structure of the monolayer have been obtained from our combined use of experimental and simulation techniques.

Structure of surfactant and phospholipid monolayers at the air/water interface modeled from neutron reflectivity data

“…As a result of this advance therefore, it may be possible in the future to gain sharper insight into biophysical processes by resolving the phase of monolayers during or as a result of molecular interactions with a range of systems includeing those involving interactions with synthetic polymers, 40 proteins, 41 DNA, 42 nanoparticles 43 or drugs. 44 . This possibility is of importance given that phase transitions occur as a result of changes in the ionic strength, 58 pH 59 and temperature 68 as well as surface pressure.…”

“…We feel that description of such a framework may lead to more successful routine exploitation in the future of monolayer data including systems that involve interactions with species such as synthetic polymers, 40 proteins, 41 DNA, 42 nanoparticles 43 or drugs. 44 Experimental Section Materials SDS (Sigma; 99.9%) was recrystallized twice from ethanol and C12TAB (Sigma; 99.9%) was recrystallized twice from acetone; each time solutions were cooled over several hours to maximize the purity. Chaindeuterated SDS (d25-SDS) and C12TAB (d25-C12TAB) were used as supplied by the ISIS Oxford Isotope Facility (Didcot, UK).…”

Interaction of testosterone-based compounds with dodecyl sulphate monolayers at the air–water interface

“…The experimental investigations that have been reported were focussed on oil 44,45 and fragrance 46,47 molecules. Only recently have we reported an interdisciplinary investigation of a drug molecule with a SDS monolayer 48 .…”

Structure and Dynamics of Nanoconfined Water Between Surfactant Monolayers

“…This shows that water molecules are able to permeate past the monolayer headgroups, as has been previously observed for SDS monolayers. [55][56][57]59 This behavior is not seen at the air-water interface, where the water intrinsic density decays monotonically, 2 as shown in SI Figure 5 interface, which suggests that water molecules are unlikely to interact strongly with a neutral substrate, as in the experiments of Dhopatkar and co-workers. 9 We note that in a symmetric system, shown in Figure 2(a), the two intrinsic densities are identical.…”