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Microstructure and biopharmaceutical performances of curcumin-loaded low-energy nanoemulsions containing eucalyptol and pinene: Terpenes’ role overcome penetration enhancement effect?

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2020
j.ejps.2019.105135_acc.pdf (1.153Mb)
Authors
Nikolić, Ines
Mitsou, Evgenia
Pantelić, Ivana
Ranđelović, Danijela
Marković, Bojan D.
Papadimitriou, Vassiliki
Xenakis, Aristotelis
Lunter, Dominique Jasmin
Zugic, Ana
Savić, Snežana D.
Article (Accepted Version)
,
Elsevier BV
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Abstract
The objective of this work was to develop low-energy nanoemulsions for enhanced dermal delivery of curcumin, using monoterpene compounds eucalyptol (EUC) and pinene (PIN) as chemical penetration enhancers. Spontaneous emulsification was the preparation method. All formulations contained 10% of the oil phase (medium-chain triglycerides (MCT), or their mixture with EUC or PIN). Formulations were stabilized by the combination of polysorbate 80 and soybean lecithin (surfactant-to-oil-ratio=1). Concentration of curcumin was set to 3 mg/ml. Average droplet diameter of all tested formulations ranged from 102 nm to 132 nm, but the ones containing monoterpenes had significantly smaller size compared to the MCT formulation. Such finding was profoundly studied through electron paramagnetic resonance spectroscopy, which proved that the presence of monoterpenes modified the nanoemulsions’ interfacial environment, resulting in droplet size reduction. The release study of curcumin (using Franz cell...s) demonstrated that the cumulative amount released after 6 h of the experiment was 10.1 ± 0.2% for the MCT nanoemulsions, 13.9 ± 0.1% and 14.0 ± 0.2% for PIN and EUC formulations, respectively. In vivo tape stripping revealed their performances in delivering curcumin into the skin, indicating the following order: EUC>MCT>PIN. The formulation with EUC was clearly the most successful, giving the highest cumulative amount of curcumin that penetrated per surface unit: 34.24±5.68 µg/cm2. The MCT formulation followed (30.62±2.61 µg/cm2) and, finally, the one with PIN (21.61±0.11 µg/cm2). These results corelated with curcumin's solubility in the chosen oils: 4.18±0.02 mg/ml for EUC, 1.67±0.04 mg/ml for MCT and 0.21±0.01 mg/ml for PIN. Probably, higher solubility in the oil phase of the nanoemulsion promoted curcumin's solubility in the superficial skin layers, providing enhanced penetration.

Keywords:
Monoterpene / Low-energy nanoemulsion / Electron paramagnetic resonance spectroscopy / Interfacial dynamics / Penetration / Curcumin
Source:
European Journal of Pharmaceutical Sciences, 2020, 142, 105135-
Publisher:
  • Elsevier BV
Projects:
  • Development of micro- and nanosystems as carriers for drugs with anti-inflammatory effect and methods for their characterization (RS-34031)
  • Micro- Nanosystems and Sensors for Electric Power and Process Industry and Environmental Protection (RS-32008)
  • bilateral project between the Republic of Serbia and the Federal Republic of Germany (Biosurfactants and biopolysaccharides/film-forming polymers as cosmetic raw materials and prospective pharmaceutical excipients: formulation of colloidal and film-forming delivery systems)
Note:
  • This is the peer-reviewed version of the article: European Journal of Pharmaceutical Sciences, 2020, 142, 105135, https://doi.org/10.1016/j.ejps.2019.105135
  • The published version: http://cer.ihtm.bg.ac.rs/handle/123456789/3309

DOI: 10.1016/j.ejps.2019.105135

ISSN: 0928-0987

WoS: 000505188900020

Scopus: 2-s2.0-85074713831
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URI
http://cer.ihtm.bg.ac.rs/handle/123456789/3386
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