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.

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

or continue here

Materials

PEGylated phospholipids (PEG-PLs)—PEG2000-DSPE (N-(Carbonyl-methoxypolyethylenglycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine, sodium salt)—purely plant-derived and synthetic raw material (1,2-distearoyl-sn-glycero-3-phosphoethanolamine DSPE and polyethylene glycol) with 95–105% of MPEG2000-PE, stearic acid purity not lower than 98%, and PEG-5000-DPPE (N-(Carbonyl-methoxypolyethylenglycol-5000)-1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine, sodium salt)—produced from vegetable and synthetic materials, i.e., natural sn-glycero-3-phosphocholine (GPC, derived from soybean), vegetable fatty acids, and synthetic polyethylene glycol, with not less than 96% of the phospholipids, and the purity of palmitic acid not less than 98%, soybean oil (Lipoid Purified Soybean Oil 700), sodium oleate (Lipoid Sodium Oleate B), and soybean lecithin (Lipoid S 75, with 70% of the phospholipids) were purchased from Lipoid GmbH (Ludwigshafen, Germany). Curcumin((E,E)-1,7-bis(4-Hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), fish oil, polysorbate 80 (polyoxyethylensorbitanmonooleate), benzyl alcohol (BA), butylated hydroxytoluene (BHT), 2,2-Diphenyl-1-picrylhydrazyl (DPPH), 2,4,6-Tris(2-pyridyl)-s-triazine (TPTZ), iron (III) chloride (FeCl₃), 5-, 12- and 16-Doxyl stearic acid, and hydrochloric acid were obtained from Sigma-Aldrich Co (St. Louis, MO, USA). Glycerol was provided by Merck KGaA (Darmstadt, Germany), and medium chain triglycerides (MCT) were purchased from Fagron GmbH & KG (Barsbüttel, Germany). Water used for the preparation of formulations as well as for analyses was ultra-pure and obtained via a GenPure apparatus (TKA Wasseranfbereitungssysteme GmbH, Neiderelbert, Germany). All other chemicals and reagents were of pharmaceutical or HPLC grade and were used without further purification.

Đoković, J.B.; Demisli, S.; Savić, S.M.; Marković, B.D.; Cekić, N.D.; Randjelovic, D.V.; Mitrović, J.R.; Lunter, D.J.; Papadimitriou, V.; Xenakis, A.; Savić, S.D. The Impact of the Oil Phase Selection on Physicochemical Properties, Long-Term Stability, In Vitro Performance and Injectability of Curcumin-Loaded PEGylated Nanoemulsions. Pharmaceutics 2022, 14, 1666. https://doi.org/10.3390/pharmaceutics14081666