J. Mater. Chem. B

Biocompatible, non- ionic oil-in-water (O/W) microemulsion was developed to encapsulate and deliver novel lipophilic polymers possessing photoacoustic properties. , In the present study a biocompatible oil-in-water (O/W) microemulsion was developed carrying short-wave infrared (SWIR) π-conjugated polymers and possessing photoacoustic properties for the first time. SWIR and NIR absorbing conjugated polymers were accomplished to be dissolved in a Food & Drug Administration (FDA) approved natural oil limonene, to formulate an O/W microemulsion using biocompatible surfactants (Span80, Labrasol®). Detailed structural characterization in the absence and presence of the polymers was performed by means of dynamic light scattering (DLS), small-angle X-ray scattering (SAXS) and electron paramagnetic resonance (EPR) spectroscopy. In terms of biological evaluation of the loaded microemulsions, inhibition of cell proliferation in various cancer cell lines without exhibiting significant cytotoxicity was tested through the MTT assay. The developed π-conjugated polymers hosted in O/W microemulsions represent a technological approach with a wide range of biomedical and bioelectronic applications and in this contribution, their photoacoustic properties are presented as a proof-of-concept

Analyzing the impact of the oil phase selection and curcumin presence on the nanoemulsion stabilizing layer using electron paramagnetic resonance spectroscopy

ANALYZING THE IMPACT OF THE OIL PHASE SELECTION AND CURCUMIN PRESENCE ON THE NANOEMULSION STABILIZING LAYER USING ELECTRON PARAMAGNETIC RESONANCE SPECTROSCOPY Jelena Đoković1*, Sotiria Demisli2, Vassiliki Papadimitriou2, Aristotelis Xenakis2, Snežana Savić1 1University of Belgrade – Faculty of Pharmacy, Department of Pharmaceutical Technology and Cosmetology, Belgrade, Serbia 2National Hellenic Research Foundation – Institute of Chemical Biology, Athens, Greece *[email protected] The stabilizing layer of nanoemulsions impacts their stability and destiny upon in vivo administration (1). The aim of this work was to gain information about the dynamics of the surfactants’ monolayer when different oils (soybean / fish) were used, and obtain data regarding the localization of curcumin (2), an active compound with many potential health benefits, using electron paramagnetic resonance (EPR) spectroscopy. Formulations were analysed using EPR technique with three different spin probes: 5-, 12- and 16-doxyl stearic acid (DSA), to investigate membrane dynamics at different depths. The results indicated that the oil type played a crucial role, not only on the structure, but also in the localization of the bioactive compound. The addition of curcumin changed the rotational correlation time (τR) values, most notably for 5-DSA, both in soybean oil and fish oil nanoemulsions, indicating its localization in the stabilizing layer, but with opposite effects. In the soybean oil nanoemulsion the addition of curcumin increased spin probe mobility, with τR decreasing from 2.18±0.60 ns to 1.66±0.61 ns, indicating a less rigid stabilizing structure, while in the fish oil formulations it resulted in a more rigid structure reflected in τR increase from 1.19±0.10 ns to 2.96±0.81 ns and 1.63±0.13 ns to 2.27±0.19 ns, for 5-DSA and 12-DSA, respectively. This study concluded that the curcumin is located in the stabilizing layer of nanoemulsions, but its impact on stabilizing layer structure depended on the oil phase selection, with particular stabilizing effects on fish oil nanoemulsions. References 1. Nikolic, I. et al. Curcumin-loaded low‐energy nanoemulsions: Linking EPR spectroscopy‐ analysed microstructure and antioxidant potential with in vitro evaluated biological activity. J. Mol. Liq. 2020, 301, 112479. 2. Griffith, O.H. and Jost, P.C. Lipid Spin Labels in Biological Membrane. In Spin Labeling, Theory and Applications; Berliner, L.J., Eds.; Academic Press: New York, NY, USA, 1976; pp 454–484 Acknowledgements This research was funded by the MESDT, Republic of Serbia through Grant Agreement with University of Belgrade – Faculty of Pharmacy No: 451-03-68/2022-14/200161 and supported by the Science Fund of the Republic of Serbia, GRANT No 7749108, Neuroimmune aspects of mood, anxiety and cognitive effects of leads/drug candidates acting at GABAA and/or sigma‐2 receptors: In vitro/in vivo delineation by nano‐ and hiPSC‐based platform - NanoCellEmоCo

Biological evaluation of oil-in-water microemulsions as carriers of benzothiophene analogues for dermal applications

During the last decade, many studies have been reported on the design and formulation of novel drug delivery systems proposed for dermal or transdermal administration. The efforts focus on the development of biocompatible nanodispersions that can be delivered to the skin and treat severe skin disorders, including cancer. In this context, oil-in-water (O/W) microemulsions have been developed to encapsulate and deliver lipophilic bioactive molecules for dermal application. An O/W biocompatible microemulsion composed of PBS buffer, Tween 80, and triacetin was assessed for its efficacy as a drug carrier of DPS-2, a lead compound, initially designed in-house to inhibit BRAFV600E oncogenic kinase. The system was evaluated through both in vitro and ex vivo approaches. The cytotoxic effect, in the presence and absence of DPS-2, was examined through the thiazolyl blue tetrazolium bromide (MTT) cell proliferation assay using various cell lines. Further investigation through Western blotting revealed that cells died of necrosis. Porcine ear skin was used as a skin model to evaluate the degree of permeation of DPS-2 through skin and assess its retention. Through the ex vivo experiments, it was clarified that encapsulated DPS-2 was distributed within the full thickness of the stratum corneum (SC) and had a high affinity to hair follicles

Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties

The aim of this study was development of biocompatible topical microemulsions (MEs) for incorporation and improved dermal delivery of sertaconazole nitrate (SN). For this purpose, phase behavior and microstructure of pseudo-ternary glycereth-7-caprylate/caprate (Emanon EV-E, EV)/cosurfactant/Capryol (TM) 90/water systems were investigated. Furhermore, the influence of these properties on the drug skin delivery was also assessed. Expansion of ME single-phase regions with the use of short chain alcohols was a consequence of the more fluid interface when compared to other investigated systems, which was confirmed by electron paramagnetic resonance spectroscopy-EPR. The chosen bicontinuous to inverted bicontinuous formulations were assessed against the ME based on polysorbate 80 as referent sample. Despite incorporation of SN within the selected formulations induced similar alternations in electrical conductivity, viscosity and pH values, obtained EPR spectra suggested different SN localization: within the oil phase (for most of the EV based formulations), or interacting with the interface (polysorbate 80 based formulation). Due to higher in vitro drug release (12.24%-18.53%), ex vivo SN penetration into porcine ear skin (dermal retention Enhancement Ratio (ERO) ranged from 2.66 to 4.25) and pronounced antifungal activity, the chosen MEs represent promising vehicles for dermal delivery of SN in treatment of cutaneous fungal infections. The biopharmaceutical and skin performance differences obtained with different formulations were possible to be explained on the basis of their physicochemical characteristics.This is the peer-reviewed version of the article: Pajic, N. B., Nikolić, I., Mitsou, E., Papadimitriou, V., Xenakis, A., Randjelović, D., Dobricic, V., Smitran, A., Cekic, N., Calija, B.,& Savić, S. D. (2018). Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties. Journal of Molecular LiquidsElsevier Science Bv, Amsterdam., 272, 746-758. [https://doi.org/10.1016/j.molliq.2018.10.002]The published version: [https://cer.ihtm.bg.ac.rs/handle/123456789/2360

The Impact of the Oil Phase Selection on Physicochemical Properties, Long-Term Stability, In Vitro Performance and Injectability of Curcumin-Loaded PEGylated Nanoemulsions

A nanotechnology-based approach to drug delivery presents one of the biggest trends in biomedical science that can provide increased active concentration, bioavailability, and safety compared to conventional drug-delivery systems. Nanoemulsions stand out amongst other nanocarriers for being biodegradable, biocompatible, and relatively easy to manufacture. For improved drug-delivery properties, longer circulation for the nanoemulsion droplets should be provided, to allow the active to reach the target site. One of the strategies used for this purpose is PEGylation. The aim of this research was assessing the impact of the oil phase selection, soybean or fish oil mixtures with medium chain triglycerides, on the physicochemical characteristics and injectability of curcumin-loaded PEGylated nanoemulsions. Electron paramagnetic resonance spectroscopy demonstrated the structural impact of the oil phase on the stabilizing layer of nanoemulsions, with a more pronounced stabilizing effect of curcumin observed in the fish oil nanoemulsion compared to the soybean oil one. The design of the experiment study, employed to simultaneously assess the impact of the oil phase, different PEGylated phospholipids and their concentrations, as well as the presence of curcumin, showed that not only the investigated factors alone, but also their interactions, had a significant influence on the critical quality attributes of the PEGylated nanoemulsions. Detailed physicochemical characterization of the NEs found all formulations were appropriate for parenteral administration and remained stable during two years of storage, with the preserved antioxidant activity demonstrated by DPPH and FRAP assays. In vitro release studies showed a more pronounced release of curcumin from the fish oil NEs compared to that from the soybean oil ones. The innovative in vitro injectability assessment, designed to mimic intravenous application, proved that all formulations tested in selected experimental setting could be employed in prospective in vivo studies. Overall, the current study shows the importance of oil phase selection when formulating PEGylated nanoemulsion

Oxidation Catalysis by Enzymes in Microemulsions

Microemulsions are regarded as “the ultimate enzyme microreactors” for liquid oxidations. Their structure, composed of water nanodroplets dispersed in a non-polar medium, provides several benefits for their use as media for enzymatic transformations. They have the ability to overcome the solubility limitations of hydrophobic substrates, enhance the enzymatic activity (superactivity phenomenon) and stability, while providing an interface for surface-active enzymes. Of particular interest is the use of such systems to study biotransformations catalyzed by oxidative enzymes. Nanodispersed biocatalytic media are perfect hosts for liquid oxidation reactions catalyzed by many enzymes such as heme peroxidases, phenoloxidases, cholesterol oxidase, and dehydrogenases. The system’s composition and structural properties are important for better understanding of nanodispersion-biocatalyst interactions

Microemulsion-based organogels containing lipase: Application in the synthesis of esters

Journal URL: http://www.springerlink.com/content/110318

Olive oil microemulsions as a biomimetic medium for enzymatic studies: Oxidation of oleuropein

Journal URL: http://www.springerlink.com/content/120382