Article Cite This: Langmuir 2019, 35, 7879−7886
pubs.acs.org/Langmuir
Structural Characterization of Reconstituted Bioactive-Loaded Nanodomains after Embedding in Films Using Electron Paramagnetic Resonance and Self-Diffusion Nuclear Magnetic Resonance Techniques Eva Abramov,† Maria Francesca Ottaviani,*,‡ Alexander I. Shames,§ Alberto Fattori,‡ and Nissim Garti*,† Downloaded via BUFFALO STATE on July 23, 2019 at 02:28:21 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.
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The Ratner Chair of Chemistry, Casali Institute of Applied Chemistry, The Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 91904, Israel ‡ Department of Pure and Applied Sciences (DiSPeA), University of Urbino, Via Ca’ le Suore 2/4, Urbino 61029, Italy § Department of Physics, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 8410501, Israel S Supporting Information *
ABSTRACT: Pharmaceutical applications of microemulsions (MEs) as drug delivery vehicles are recently gaining scientific and practical interests. Most MEs are able to solubilize bioactive molecules, but, at present, they cannot guarantee either controlled release of the drugs or significant advantage in the bioavailability of the bioactives. This study proposes to incorporate the modified ME structures, or nanodomains, into a natural polymeric film, to be used as a stable and capacious reservoir of drug-loaded nanodomains. These nanodomainloaded films may release the nanodroplets along with the drug molecules in a slow and controlled way. Gellan gum, an anionic polysaccharide, was used in aqueous solution as the film former, and curcumin, hydrophobic polyphenol, served as the guest molecule in the loaded systems. Films were prepared by using empty and curcumin-loaded MEs. It is imperative to verify the persistence of the ME structure upon the dissolution of the film mimicking its behavior when in contact with a human physiological aqueous environment via reaching the cell membranes. For this purpose, the films were dissolved, and the reconstituted ME structure was compared with the ME structure before film formation. Characterization of these structures, before and after dissolution, was achieved using electron paramagnetic resonance (EPR) and self-diffusion nuclear magnetic resonance (SD-NMR) techniques. Specific spin probes were inserted in the system, and a computer-aided analysis of the EPR spectra was performed to provide information on nanodomain microstructure assemblies. In addition, the SD-NMR profile of each component was analyzed to extract information on the diffusivity of the ME components before film formation and after ME reconstitution. The EPR and SD-NMR results were in good agreement to each other. The most important finding was that, after film dissolution, the ME nanodomains were reversibly and spontaneously reformed. It was also found that the film did not perturb the ME-nanodomain structure embedded in it. The film remained transparent and the bioactive curcumin was easily solubilized into the ME-droplet/water interface even after film dissolution. The combined techniques confirmed that the film constituted by bioactive-loaded MEs can serve as novel drug delivery vehicles.
1. INTRODUCTION
semi-solid vehicles for drug delivery because they provide several important advantages such as thermodynamic stability, low viscosity and Newtonian behavior, high surface area, very small and almost monodispersed size of the droplets. These characteristics well improve the ME chances to adhere to physiological membranes and permeate them, in order to enhance their transport across human membranes.5−7
Microemulsions (MEs) are small (
