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Nonionic surfactants have been widely used in agri-sprays to enhance the solubility and mobility of pesticides, but what happens when pesticides become solubilized into surfactant micelles remains poorly characterized. To facilitate physical characterisations, we used the nonionic surfactant hexaethylene glycol monododecyl ether (C12E6) as a model system to solubilize 4 pesticides including Cyprodinil (CP), Diuron (DN), Azoxystrobin (AZ) and Difenoconazole (DF). The investigation focused on the influence of solubilizate and temperature in driving changes to the micellar nanostructures. Dynamic light scattering (DLS), cryogenic transmission electron microscopy (Cryo-TEM) and small-angle neutron scattering (SANS) measurements were used to reveal changes to the micellar structure before and after pesticide solubilisation. Nuclear magnetic resonance (NMR) was also applied to investigate the solubility and location of each pesticide in the micelles. Pesticides clearly altered the micellar structure, by increasing the aggregation number and micellar lengths, whilst shrinking and dehydrating the shells, leading to a consequent decrease in the dispersion cloud points. Increases in temperature affected micellar structures in a similar way. Thus, temperature increases and the solubilisation of pesticides can both make the surfactant effectively more hydrophobic, altering the micellar nanostructures and shifting the pesticide location within the micelles. These changes subsequently implicate how pesticides are delivered into plants through the natural wax films.

Hypothesis Surfactants have been widely used as adjuvants in agri-sprays to enhance the solubility of pesticides in foliar spray deposits and their mobility through leaf cuticles. Previously, we have characterised pesticide solubilisation in nonionic surfactant micelles, but what happens when pesticides become solubilised in anionic, cationic and zwitterionic and their mixtures with nonionic surfactants remain poorly characterised. Experiments To facilitate characterisations by SANS and NMR, we used nonionic surfactant hexaethylene glycol monododecyl ether (C12E6), anionic sodium dodecylsulphate (SDS), cationic dodecyltrimethylammonium bromide (DTAB) and zwitterionic dodecylphosphocholine (C12PC) as model adjuvant systems to solubilise 3 pesticides, Cyprodinil (CP), Azoxystrobin (AZ) and Difenoconazole (DF), representing different structural features. The investigation focused on the influence of solubilisates in driving changes to the micellar nanostructures in the absence or presence of electrolytes. NMR and NOESY were applied to investigate the solubility and location of each pesticide in the micelles. SANS was used to reveal subtle changes to the micellar structures due to pesticide solubilisation with and without electrolytes. Findings Unlike nonionic surfactants, the ionic and zwitterionic surfactant micellar structures remain unchanged upon pesticide solubilisation. Electrolytes slightly elongate the ionic surfactant micelles but have no effect on nonionic and zwitterionic surfactants. Pesticide solubilisation could alter the structures of the binary mixtures of ionic/zwitterionic and ionic/nonionic micelles by causing elongation, shell shrinkage and dehydration, with the exact alteration being determined by the molar ratio in the mixture.

During the formulation of therapeutic monoclonal antibodies (mAbs), nonionic surfactants are commonly added to attenuate structural rearrangement caused by adsorption/desorption at interfaces during processing, shipping, and storage. We examined the adsorption of a mAb (COE-3) at the SiO2/water interface in the presence of pentaethylene glycol monododecyl ether (C12E5), polysorbate 80 (PS80-20EO), and a polysorbate 80 analogue with seven ethoxylates (PS80-7EO). Spectroscopic ellipsometry was used to follow COE-3 dynamic adsorption, and neutron reflection was used to determine interfacial structure and composition. Neither PS80-20EO nor C12E5 had a notable affinity for COE-3 or the interface under the conditions studied and thus did not prevent COE-3 adsorption. In contrast, PS80-7EO did coadsorb but did not influence the dynamic process or the equilibrated amount of absorbed COE-3. Near equilibration, COE-3 underwent structural rearrangement and PS80-7EO started to bind the COE-3 interfacial layer and subsequently formed a well-defined surfactant bilayer via self-assembly. The resultant interfacial layer comprised an inner mAb layer of about 70 Å thickness and an outer surfactant layer of a further 70 Å, with distinct transitional regions across the mAb–surfactant and surfactant–bulk water boundaries. Once formed, such interfacial layers were very robust and worked to prevent further mAb adsorption, desorption, and structural rearrangement. Such robust interfacial layers could be anticipated to exist for formulated mAbs stored in type II glass vials; further research is required to understand the behavior of these layers for siliconized glass syringes.

Hypothesis Nonionic surfactants are used as adjuvants in agri-sprays to stabilise pesticides, but what happens when pesticide-loaded micelles are brought into direct contact with plant leaves? As pesticide solubilisation dehydrates the micellar shell and increases the effective hydrophobicity of the surfactant, we hypothesise that these micelles would uptake plant waxes and alter the amount of pesticide solubilized as a result of the re-equilibrating process. Experiments The solubility of the pesticide cyprodinil (CP) and its effect on the shape of hexaethylene glycol monododecyl ether (C12E6) micelles were studied using changes in cloud point, nuclear magnetic resonance (NMR), cryogenic transmission electron microscopy (Cryo-TEM) and small-angle neutron scattering (SANS). Similarly, the solubility of wheat leaf waxes was examined, as was the effect of adding leaf waxes to pre-dissolved cyprodinil in micellar C12E6. Findings Wax solubilisation caused pesticide release and shell hydration, and shortened the length of the cylindrical micelles of the CP loaded C12E6. Temperature increase led to a significant rise in the amount of the dissolved waxes, increased pesticide release, increased micellar length, and caused shrinkage and dehydration of the shell. This study indicates that agrochemical sprays are capable of dissolving leaf waxes, and may trigger pesticide release from surfactant micelles upon contact with plant surfaces.

The physical stability of a monoclonal antibody (mAb) solution for injection in a prefilled syringe may in part depend on its behavior at the silicone oil/water interface. Here, the adsorption of a mAb (termed COE-3) and its fragment antigen-binding (Fab) and crystallizable (Fc) at the oil/water interface was measured using neutron reflection. A 1.4 ± 0.1 μm hexadecane oil film was formed on a sapphire block by a spin-freeze-thaw process, retaining its integrity upon contact with the protein solutions. Measurements revealed that adsorbed COE-3 and its Fab and Fc fragments retained their globular structure, forming layers that did not penetrate substantially into the oil phase. COE-3 and Fc were found to adsorb flat-on to the interface, with denser 45 and 42 Å inner layers, respectively, in contact with the oil and a more diffuse 17-21 Å outer layer caused by fragments adsorbing in a tilted manner. In contrast, Fab fragments formed a uniform 60 Å monolayer. Monolayers were formed under all conditions studied (10-200 ppm, using three isotopic contrasts), although changes in packing density across the COE-3 and Fc layers were observed. COE-3 had a higher affinity to the interface than either of its constituent fragments, while Fab had a lower interfacial affinity consistent with its higher net surface charge. This study extends the application of high-resolution neutron reflection measurements to the study of protein adsorption at the oil/water interface using an experimental setup mimicking the protein drug product in a siliconized prefilled syringe.

During the formulation of therapeutic monoclonal antibodies (mAbs), nonionic surfactants are commonly added to attenuate structural rearrangement caused by adsorption/desorption at interfaces during processing, shipping, and storage. We examined the adsorption of a mAb (COE-3) at the SiO