Particle-stabilized oil-in-water emulsions as a platform for topical lipophilic drug delivery.

Low-environmental-impact emulsion systems for transdermal drug delivery in topical treatment have gained increasing interest. However, low stability and adverse systemic side effects severely decrease their efficiency. This study proposed a stable oil-in-water (O/W) emulsion loaded with bifonazole (BFZ) as a lipophilic drug stabilized by poly(2-isopropoxy-2-oxo-1,3,2-dioxaphospholane)-modified cellulose nanocrystals (CNC-g-PIPP) as vehicles for topical delivery of lipophilic drugs. We fully characterized stability, BFZ-loaded particle-stabilized emulsions (PEs) for morphology, droplet size, and its distribution. In addition, we evaluated the in vitro drug-releasing capacity and in vitro skin permeation of BFZ in a porcine skin animal model using a side-bi-side® diffusion cell. An O/W BFZ-loaded emulsion stabilized with CNC-g-PIPP particles (BFZ-loaded CP-PE) with a small mean droplet size of 2.54 ± 1.39 µm was developed and was stable for > = 15 days without a significant change in droplet size. The BFZ-loading efficiency in PEs was 83.1 %. BFZ was slowly released over an extended period, and the releasing ratio from BFZ-loaded CP-PE was only 17 % after 48 h. The BFZ-loaded CP-PE showed a ∼4.4-fold increase in BFZ permeation and penetration compared to a conventional surfactant-stabilized emulsion and BFZ control solution. Fluorescence-labeling studies showed that BFZ-loaded CP-PE could well penetrate skin layers from the stratum corneum (SC) to the dermis. In addition, histopathology studies of porcine skin treated with the PE formulation showed an intact SC with unaltered adjacent structures and no observed signs of inflammation. Therefore, the proposed CP-PE shows great potential as a transdermal drug carrier for enhancing lipophilic drug permeation.

Effect of Stabilizing Particle Size on the Structure and Properties of Liquid Marbles.

A liquid marble (LM) describes a liquid droplet that is wrapped by nonwetting micro- or nanoparticles and therefore obtains characteristics of a solid powder particle. Here, we investigate the effect of the stabilizing particle size on the resulting structure and properties of the LM. We synthesize a series of polystyrene particles with ultrathin coatings of heptadecafluorooctanesulfonic acid-doped polypyrrole with diameters ranging between 1 and 1000 µm by an aqueous chemical oxidative seeded polymerization of pyrrole. The methodology produced a set of hydrophobic particles with similar surface characteristics to allow the formation of LMs and to probe size effects in the LM formation and stabilization efficiency. We found that particles with a size above 20 µm adsorb as a particle monolayer to the surface of the LM, while smaller particles are adsorbed as ill-defined, multilayered aggregates. These results indicate that the balance between particle-particle interaction and gravity is an important parameter to control the surface structure of the LMs. The assembly behavior and size of the particles also correlated with the mechanical integrity of the LM against fall impact. The mechanical resistance was affected by the gap distance between the inner liquid of the LM and supporting substrate, the capillary forces acting between the particles at the LM surface, and the potential energy that depended on the particle size. Last, we demonstrate that the broadband light-absorbing properties of the polypyrrole shell also allow manipulating the evaporation rate of the inner liquid.

Particle Monolayer-Stabilized Light-Sensitive Liquid Marbles from Polypyrrole-Coated Microparticles.

Liquid marbles are water droplets coated with solid particles that prevent coalescence and allow storage, transport, and handling of liquids in the form of a powder. Here, we report on the formation of liquid marbles that are stabilized entirely by a single monolayer of solid particles and thus minimize the amount of required solid material. As stabilizing particles, we synthesize relatively monodisperse, 80 µm-sized polystyrene (PS) particles coated with heptadecafluorooctanesulfonic acid-doped polypyrrole (PPy-C8F) shell (PS/PPy-C8F particles) by aqueous chemical oxidative seeded polymerization of pyrrole using FeCl3 as an oxidant and heptadecafluorooctanesulfonic acid as a hydrophobic dopant. We characterize the physicochemical properties of the particles as a function of the PPy-C8F loading. Laser diffraction particle size analyses of dilute aqueous suspensions indicate that the polymer particles disperse stably in water medium before and after coating with the PPy-C8F shell. X-ray photoelectron spectroscopy studies indicate the formation of a PPy-C8F shell around the PS seed particles, which was further supported by deflated morphologies observed by scanning electron microscopy after extraction of the PS component from the PS/PPy-C8F particles. We investigate the performance of the dried PS/PPy-C8F particles to stabilize liquid marbles. Stereo- and laser microscope observations, as well as gravimetric studies, confirm that the PS/PPy-C8F particles adsorb to the water droplet surface in the form of a particle monolayer with the characteristic hexagonal close-packed structure expected for spherical (colloidal) particles. Mechanical integrity of the liquid marble increases with an increase of PPy-C8F loading of the PS/PPy-C8F particles. The water contact angle of the PS/PPy-C8F particles at air-water interface increases from 82 ± 12° to 102 ± 17° with an increase of PPy-C8F loading. This increase in water contact angle directly correlates with the shape of the LM, with higher contact angles giving more spherical LMs. Furthermore, the broadband light absorption properties of the PPy coating was used to control evaporation rate of the enclosed water phase on demand by irradiation with a near-infrared laser. The evaporation rate could be finely controlled by the thickness of the PPy-C8F shell of the particles stabilizing the liquid marbles.

Light-Driven Locomotion of Bubbles.

Remotely controlling the movement of small objects is a challenging research topic, which can realize the transportation of materials. In this study, remote locomotion control of particle-stabilized bubbles on a planar water surface by near-infrared laser or sunlight irradiation is demonstrated. A light-induced Marangoni flow was utilized to induce the locomotion of the bubbles on water surface, and the timing and direction of the locomotion can be controlled by irradiation timing and direction on demand. The velocity, acceleration, and force of the bubbles were analyzed. It was also confirmed that the bubbles can work as light-driven towing engines to pull other objects. Furthermore, it was demonstrated that the bubbles can work as an adhesive to bond two solid substrates by application of compressive stress under water. Such remote transport of the materials, pulling of the objects by light, and controlling the release of gas on demand should open up a wide field of conceivable applications.

Influence of particle size on extraction from a charged bed - toward liquid marble formation.

The interactions between particles and the role of their physical properties are not well understood for the electrostatic formation of liquid marbles. Here we focus initially on the impact of increasing particle diameter (notionally 20 to 140 µm) on the ease of particle extraction from an advancing bed of charged particles beneath an earthed, suspended water droplet. A larger particle diameter increased the ease of extraction, due to decreased interparticle cohesion, with increased potential applied to the particle bed. Whilst particle extraction is a crucial step in liquid marble formation, transport to the droplet and subsequent coating and stabilisation of the liquid is also significant. Further investigation highlighted that the smaller particle diameters afforded increased liquid stabilisation due to increased coverage and smaller interstitial spaces between particles on the liquid surface. Optimal conditions for controllable liquid marble formation using electrostatics was postulated as a trade-off between drop-bed separation distance, applied potential and kinetics of coating when studying impact of particle size. Furthermore, preliminary modelling, utilising weakest-link statistics and fracture mechanics, of the experimental data was undertaken to focus on development of the relationship between particle properties and extractability in the presence of electrostatics. This model represents a step towards predicting the suitability of particles for use in the electrostatic formation of liquid marbles prior to undertaking experimental work.

Surface Grafting Polyphosphoesters on Cellulose Nanocrystals To Improve the Emulsification Efficacy.

Particle-stabilized emulsion systems have been developed to address the problematic properties of conventional surfactants. However, the nature and properties of the fine particles used in such systems remain a critical issue for stability enhancement. Herein, we describe a thermoswitchable oil-in-water (O/W) particle-stabilized emulsion that exhibits improved stability due to the addition of cellulose nanocrystals (CNCs) modified with poly[2-isopropoxy-2-oxo-1,3,2-dioxaphospholane] (PIPP), which exhibits relatively good biocompatibility and biodegradability. Various parameters, such as surface activity, concentration of particles, polarity of solvents, and temperatures, on the formation of emulsions with CNCs grafted with PIPP (CNC-g-PIPP) were investigated. Results showed that the surface activity of CNC-g-PIPP was significantly improved compared with the unmodified material. Heptane-in-water particle-stabilized emulsions with CNC-g-PIPP were stably formed, and the effect of temperature on the stability of the emulsions was characterized. CNC-g-PIPP exhibited function as an effective particulate emulsifier at 4 °C because of the strong adsorption at the oil-water interface. However, the emulsions rapidly disintegrated at 45 °C, which is above the low critical solution temperature of PIPP on CNC, as the hydrophobized CNC-g-PIPP desorbed from the oil-water interface. Based on these findings, a thermally induced reversible emulsification/demulsification was presented. The resulting switchable particle-stabilized emulsion based on CNC-g-PIPP shows promise for the ability to control the stability of an emulsion in response to temperature, which is attractive for use in biological applications.

pH-Responsive Aqueous Bubbles Stabilized With Polymer Particles Carrying Poly(4-vinylpyridine) Colloidal Stabilizer.

Free radical dispersion polymerization was conducted to synthesize near-monodispersed, micrometer-sized polystyrene (PS) particles carrying pH-responsive poly(4-vinylpyridine) (P4VP) colloidal stabilizer (P4VP-PS particles). The P4VP-PS particles were extensively characterized in terms of morphology, size, size distribution, chemical composition, surface chemistry, and pH-response using optical and scanning electron microscopies, elemental microanalysis, X-ray photoelectron spectroscopy, laser diffraction particle size analysis, and zeta potential measurement. The P4VP-PS particles can work as a pH-responsive stabilizer of aqueous bubbles by adsorption at the air-water interface. At and above pH 4.0, where the particles have partially protonated/non-protonated P4VP stabilizer with relatively hydrophobic character, particle-stabilized bubbles were formed. Optical and scanning electron microscopy studies confirmed that the P4VP-PS particles were adsorbed at the air-water interface of the bubbles in aqueous media. At and below pH 3.0, where the particles have cationic P4VP stabilizer with water-soluble character, no bubble was formed. Rapid disruption of the bubbles can be induced by decreasing the pH; the addition of acid caused the in situ protonation of pyridine groups in P4VP, which impart water-soluble character to the P4VP stabilizer, and the P4VP-PS particles were desorbed from the air-water interface. The bubble stabilization/destabilization cycles could be repeated at least five times.