Encapsulation of cannabidiol in oil-in-water nanoemulsions and nanoemulsion-filled hydrogels: A structure and biological assessment study.

HYPOTHESIS: Lipophilic cannabidiol can be solubilized in oil-in water nanoemulsions, which can then be impregnated into chitosan hydrogels forming another colloidal system that will facilitate cannabidiol's release. The delivery from both systems was compared, alongside structural and biological studies, to clarify the effect of the two carriers' structure on the release and toxicity of the systems. EXPERIMENTS: Oil-in-water nanoemulsions (NEs) and the respective nanoemulsion-filled chitosan hydrogels (NE/HGs) were formulated as carriers of cannabidiol (CBD). Size, polydispersity and stability of the NEs were evaluated and then membrane dynamics, shape and structure of both systems were investigated with EPR spin probing, SAXS and microscopy. Biocompatibility of the colloidal delivery systems was evaluated through cytotoxicity tests over normal human skin fibroblasts. An ex vivo permeation protocol using porcine ear skin was implemented to assess the release of CBD and its penetration through the skin. FINDINGS: Incorporation of the NEs in chitosan hydrogels does not significantly affect their structural properties as evidenced through SAXS, EPR and confocal microscopy. These findings indicate the successful development of a novel nanocarrier that preserves the NE structure with the CBD remaining encapsulated in the oil core while providing new rheological properties advantageous over NEs. Moreover, NE/HGs proved to be more efficient as a carrier for the release of CBD. Cell viability assessment revealed high biocompatibility of the proposed colloids.

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 nanoemulsions.

Development and Study of Nanoemulsions and Nanoemulsion-Based Hydrogels for the Encapsulation of Lipophilic Compounds.

Biocompatible nanoemulsions and nanoemulsion-based hydrogels were formulated for the encapsulation and delivery of vitamin D3 and curcumin. The aforementioned systems were structurally studied applying dynamic light scattering (DLS), electron paramagnetic resonance (EPR) spectroscopy and viscometry. In vitro studies were conducted using Franz diffusion cells to investigate the release of the bioactive compounds from the nanocarriers. The cytotoxicity of the nanoemulsions was investigated using the thiazolyl blue tetrazolium bromide (MTT) cell proliferation assay and RPMI 2650 nasal epithelial cells as in vitro model. DLS measurements showed that vitamin D3 and curcumin addition in the dispersed phase of the nanoemulsions caused an increase in the size of the oil droplets from 78.6 ± 0.2 nm to 83.6 ± 0.3 nm and from 78.6 ± 0.2 nm to 165.6 ± 1.0 nm, respectively. Loaded nanoemulsions, in both cases, were stable for 60 days of storage at 25 °C. EPR spectroscopy revealed participation of vitamin D3 and curcumin in the surfactants monolayer. In vitro release rates of both lipophilic compounds from the nanoemulsions were comparable to the corresponding ones from the nanoemulsion-based hydrogels. The developed o/w nanoemulsions did not exhibit cytotoxic effect up to the concentration threshold of 1 mg/mL in the cell culture medium.