Evaluating the ready biodegradability of two poorly water-soluble substances: comparative approach of bioavailability improvement methods (BIMs).
ABSTRACT: Difficulties encountered in estimating the biodegradation of poorly water-soluble substances are often linked to their limited bioavailability to microorganisms. Many original bioavailability improvement methods (BIMs) have been described, but no global approach was proposed for a standardized comparison of these. The latter would be a valuable tool as part of a wider strategy for evaluating poorly water-soluble substances. The purpose of this study was to define an evaluation strategy following the assessment of different BIMs adapted to poorly water-soluble substances with ready biodegradability tests. The study was performed with two poorly water-soluble chemicals-a solid, anthraquinone, and a liquid, isodecyl neopentanoate-and five BIMs were compared to the direct addition method (reference method), i.e., (i) ultrasonic dispersion, (ii) adsorption onto silica gel, (iii) dispersion using an emulsifier, (iv) dispersion with silicone oil, and (v) dispersion with emulsifier and silicone oil. A two-phase evaluation strategy of solid and liquid chemicals was developed involving the selection of the most relevant BIMs for enhancing the biodegradability of tested substances. A description is given of a BIM classification ratio (R BIM), which enables a comparison to be made between the different test chemical sample preparation methods used in the various tests. Thereby, using this comparison, the BIMs giving rise to the greatest biodegradability were ultrasonic dispersion and dispersion with silicone oil or with silicone oil and emulsifier for the tested solid chemical, adsorption onto silica gel, and ultrasonic dispersion for the liquid one.
Project description:In this study, a water-silicone oil biphasic system was developed to enhance the biodegradation of monochlorobenzene (CB) by Delftia tsuruhatensis LW26. Compared to the single phase, the biphasic system with a suitable silicone oil fraction (v/v) of 20% allowed a 2.5-fold increase in the maximum tolerated CB concentration. The CB inhibition on D. tsuruhatensis LW26 was reduced in the presence of silicone oil, and the electron transport system activity was maintained at high levels even under high CB stress. Adhesion of cells to the water-oil interface at the water side was observed using confocal laser scanning microscopy. Nearly 75% of cells accumulated on the interface, implying that another interfacial substrate uptake pathway prevailed besides that initiated by cells in the aqueous phase. The 8-fold increase in cell surface hydrophobicity upon the addition of 20% (v/v) silicone oil showed that silicone oil modified the surface characteristics of D. tsuruhatensis LW26. The protein/polysaccharide ratio of extracellular polymeric substances (EPS) from D. tsuruhatensis LW26 presented a 3-fold enhancement. These results suggested that silicone oil induced the increase in the protein content of EPS and rendered cells hydrophobic. The resulting hydrophobic cells could adhere on the water-oil interface, improving the mass transfer by direct CB uptake from silicone oil.
Project description:Mosquito legs have a unique highly water-repellent surface structure. While being beneficial to mosquitoes, the water-repellence of the tarsi enhances the wettability of hydrophobic substances such as oils. This high wettability induces strong attraction forces on a mosquito's legs (up to 87% of the mosquito's weight) towards the oil. We studied the landing behaviour of mosquitoes on oil-coated surfaces and observed that the mosquito contact time was reduced compared to that on hydrophilic-liquid-coated surfaces, suggesting that the oil coating induces an escape response. The observed escape behaviour occurred consistently with several hydrophobic liquids, including silicone oil, which is used globally in personal care products. As the repellent effect is similar to multiple hydrophobic substances, it is likely to be mechanically stimulated owing to the physical properties of the hydrophobic liquids and not due to chemical interactions. On human skin, the contact time was sufficiently short to prevent mosquitoes from starting to blood-feed. The secretion of Hippopotamus amphibius, which has physical properties similar to those of low-viscosity silicone oil, also triggered an escape response, suggesting that it acts as a natural mosquito repellent. Our results are beneficial to develop new, safe, and effective mosquito-repellent technologies.
Project description:We report the preparation of highly transparent oil-in-water Pickering emulsions using contrast-matched organic nanoparticles. This is achieved via addition of judicious amounts of either sucrose or glycerol to an aqueous dispersion of poly(glycerol monomethacrylate)56-poly(2,2,2-trifluoroethyl methacrylate)500 [PGMA-PTFEMA] diblock copolymer nanoparticles prior to high shear homogenization with an equal volume of n-dodecane. The resulting Pickering emulsions comprise polydisperse n-dodecane droplets of 20-100 ?m diameter and exhibit up to 96% transmittance across the visible spectrum. In contrast, control experiments using non-contrast-matched poly(glycerol monomethacrylate)56-poly(benzyl methacrylate)300 [PGMA56-PBzMA300] diblock copolymer nanoparticles as a Pickering emulsifier only produced conventional highly turbid emulsions. Thus contrast-matching of the two immiscible phases is a necessary but not sufficient condition for the preparation of highly transparent Pickering emulsions: it is essential to use isorefractive nanoparticles in order to minimize light scattering. Furthermore, highly transparent oil-in-water-in-oil Pickering double emulsions can be obtained by homogenizing the contrast-matched oil-in-water Pickering emulsion prepared using the PGMA56-PTFEMA500 nanoparticles with a contrast-matched dispersion of hydrophobic poly(lauryl methacrylate)39-poly(2,2,2-trifluoroethyl methacrylate)800 [PLMA39-PTFEMA800] diblock copolymer nanoparticles in n-dodecane. Finally, we show that an isorefractive oil-in-water Pickering emulsion enables fluorescence spectroscopy to be used to monitor the transport of water-insoluble small molecules (pyrene and benzophenone) between n-dodecane droplets. Such transport is significantly less efficient than that observed for the equivalent isorefractive surfactant-stabilized emulsion. Conventional turbid emulsions do not enable such a comparison to be made because the intense light scattering leads to substantial spectral attenuation.
Project description:Currently, polymer-based prefillable syringes are being promoted to the pharmaceutical market because they provide an increased break resistance relative to traditionally used glass syringes. Despite this significant advantage, the possibility that barrel material can affect the oligomeric state of the protein drug exists. The present study was designed to compare the effect of different syringe materials and silicone oil lubrication on the protein aggregation. The stability of a recombinant fusion protein, abatacept (Orencia), and a fully human recombinant immunoglobulin G1, adalimumab (Humira), was assessed in silicone oil-free (SOF) and silicone oil-lubricated 1-mL glass syringes and polymer-based syringes in accelerated stress study. Samples were subjected to agitation stress, and soluble aggregate levels were evaluated by size-exclusion chromatography and verified with analytical ultracentrifugation. In accordance with current regulatory expectations, the amounts of subvisible particles resulting from agitation stress were estimated using resonant mass measurement and dynamic flow-imaging analyses. The amount of aggregated protein and particle counts were similar between unlubricated polymer-based and glass syringes. The most significant protein loss was observed for lubricated glass syringes. These results suggest that newly developed SOF polymer-based syringes are capable of providing biopharmaceuticals with enhanced physical stability upon shipping and handling.
Project description:Fish oil consists of omega-3 fatty acids which play an important role in human health. Its susceptibility to oxidation causes considerable degradation during the processing and storage of food products. Accordingly, encapsulation of this ingredient through freeze drying was studied with the aim of protecting it against environmental conditions. Gum arabic (GA) was used as the wall material for fish oil nanoencapsulation where tween 80 was applied as the emulsifier. A water-in-oil (W/O) emulsion was prepared by sonication, containing 6% fish oil dispersed in aqueous solutions including 20% and 25% total wall material. The emulsion was sonicated at 24 kHz for 120 s. The emulsion was then freeze-dried and the nanocapsules were incorporated into probiotic fermented milk, with the effects of nanocapsules examined on the milk. The results showed that the nanoparticles encapsulated with 25% gum arabic and 4% emulsifier had the highest encapsulation efficiency (EE) (87.17%) and the lowest surface oil (31.66 mg/100 kg). Using nanoencapsulated fish oil in fermented milk significantly (p<0.05) increased the viability of Lactobacillus plantarum as well as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) contents. The fermented milk sample containing fish oil nanoencapsulated with 25% wall material and 4% emulsifier yielded the greatest probiotic bacterial count (8.41 Log CFU/mL) and the lowest peroxide value (0.57 mEq/kg). Moreover, this sample had the highest EPA and DHA contents. Utilizing this nanoencapsulated fish oil did not adversely affect fermented milk overall acceptance. Therefore, it can be used for fortification of low fat probiotic fermented milk.
Project description:Characterizing protein aggregates in the presence of silicone oil is a long standing challenge for the pharmaceutical industry. Silicone oil is often used as a lubricant in devices that deliver and store therapeutic protein products and has been linked to protein aggregation, which can compromise a drug's effectiveness or cause autoimmune responses in patients. Most traditional technologies cannot quantitatively distinguish protein aggregates and silicone oil in their native formulations for sizes less than 5 ?m. We use holographic video microscopy to study protein aggregation to demonstrate its capability to quantitatively distinguish protein aggregates and silicone oil in the presence of varying amounts of the surfactants SDS and polysorbate 80 in the size range of 0.5-10 ?m without the need for dilution or special sample preparation. We show that SDS denatures proteins and stabilizes silicone oil. We also show that polysorbate 80 may limit protein aggregate formation if it is added to an IgG solution before introducing silicone oil.
Project description:We report a novel surgical sandwich technique using a combination of intraocular perfluoropropane (C3F8) and silicone oil for inferior retinal detachment (RD). After conventional pars plana vitrectomy and posterior vitreous detachment induction, fluid-gas exchange using 14% C3F8was done. This was followed by silicone oil injection using automated infusion pump to 50% fill of the vitreous cavity under direct visualization to achieve formation of two bubbles - gas bubble superiorly and silicone oil inferiorly. The patient was subsequently asked to maintain upright position. The two immiscible bubbles of C3F8and silicone oil provide tamponade to superior and inferior retina, respectively. With time, gas bubble reduces in size with a gradual superior shift of silicone oil. This novel sandwich technique achieves complete attachment of retina and reduces the risk of retinal redetachment in inferior RDs by adequately tamponading the inferior retina.
Project description:Subunit vaccines consisting of highly purified antigens require the presence of adjuvants to create effective and long-lasting protective immunity. Advances on adjuvant research include designing combination adjuvants which incorporate two or more adjuvants to enhance vaccine efficacy. Previously, an oil-in-water emulsion adjuvant (OW-14) composed of mineral oil and an inexpensive gum Arabic emulsifier has been reported demonstrating enhanced and robust immune responses when used as an adjuvant in swine subunit vaccines. This study presents a modified version of OW-14 prepared with food-grade Quillaja saponin extract (OWq). In new OWq emulsion, saponin extract served as an emulsifier for stabilization of emulsion droplets and as an immunoactive compound. The use of saponins allowed to reduce the required amount of emulsifier in the original OW-14. However, emulsion stabilized with saponins demonstrated extended physical stability even at elevated temperature (37°C). The two-dose vaccination with a classical swine fever virus (CSFV) glycoprotein E2-based vaccine formulated with OWq produced higher levels of E2-specific IgG and virus neutralizing antibodies in pigs in contrast with animals that received the vaccine adjuvanted with oil only. In addition, new OWq adjuvant was safe to use in the vaccination of pigs.
Project description:Silicone microspheres are exceedingly difficult to make. Here, polydimethylsiloxane microspheres (?1 ?m diameter) are synthesized using ultrasonic spray pyrolysis, the first demonstration of a scalable synthetic procedure for crosslinked silicone microspheres. This continuous, aerosol process is also used to directly produce fluorescent, magnetic, and copolymeric derivatives; the potential biomedical applications of these microspheres are explored.