Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024;19(23):1879-1894.
doi: 10.1080/17435889.2024.2379757. Epub 2024 Aug 2.

Antitumoral melatonin-loaded nanostructured lipid carriers

Lorena Bonilla-Vidal  1   2 , Marta Świtalska  3 , Marta Espina  1   2 , Joanna Wietrzyk  3 , Maria Luisa García  1   2 , Eliana B Souto  4 , Anna Gliszczyńska  5 , Elena Sánchez-López  1   2
Affiliations

Antitumoral melatonin-loaded nanostructured lipid carriers

Lorena Bonilla-Vidal et al. Nanomedicine (Lond). 2024.

Abstract

Aim: Cancer constitutes the second leading cause of death worldwide, with conventional therapies limited by significant side effects. Melatonin (MEL), a natural compound with antitumoral properties, suffers from instability and low solubility. To overcome these issues, MEL was encapsulated into nanostructured lipid carriers (MEL-NLC) containing rosehip oil to enhance stability and boost its antitumoral activity.Methods: MEL-NLC were optimized by a design of experiments approach and characterized for their physicochemical properties. Stability and biopharmaceutical behavior were assessed, along with interaction studies and in vitro antitumoral efficacy against various cancer cell lines.Results: Optimized MEL-NLC exhibited desirable physicochemical characteristics, including small particle size and sustained MEL release, along with long-term stability. In vitro studies demonstrated that MEL-NLC selectively induced cytotoxicity in several cancer cell lines while sparing healthy cells.Conclusion: MEL-NLC represent a promising alternative for cancer, combining enhanced stability and targeted antitumoral activity, potentially overcoming the limitations of conventional treatments.

Keywords: antitumoral; lipid nanoparticles; melatonin; nanostructured lipid carriers; natural compounds; rosehip oil.

Plain language summary

Despite current advances, cancer is the second cause of death worldwide, but conventional therapies have side effects and limited efficacy. Natural therapies are emerging as suitable alternatives and, among them, Melatonin is a well-known compound with antitumoral properties. However, it is degraded by light, decreasing its therapeutical activity. In order to effectively deliver Melatonin into cancer cells, it has been encapsulated into biodegradable nanoparticles containing rosehip oil, which may boost the antitumoral properties. These nanoparticles have been optimized, showing a small size and a high Melatonin encapsulation, sustained drug release and good stability. Furthermore, in vitro studies demonstrated antitumoral activity against several cancer cell lines, also showing a high internalization inside them. Moreover, studies conducted using chicken embryonated eggs, showed that nanoparticles were non-toxic, thus confirming its promising therapeutical applications.

PubMed Disclaimer

Conflict of interest statement

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Figures

Figure 1.
Figure 1.
Design of experiments (DoE) results. (A) Pareto's chart of the independent variables effect for mean average size (Zav). (B) Pareto's chart of the independent variables effect for polydispersity index (PI). (C) Surface response of the concentration of MEL and SL regarding to the lipid phase influence on zeta potential (ZP). (D) Surface response of the concentration of MEL and Lipid phase influence on encapsulation efficiency (EE).
Figure 2.
Figure 2.
Characterization of optimized MEL-NLC and their components. (A) Differential scanning calorimetry (DSC) curves. (B) X-ray diffraction (XRD). (C) Fourier-transform infrared (FTIR).
Figure 3.
Figure 3.
Backscattering profiles of MEL-NLC stored at different temperatures. (A) 37 °C, (B) 25 °C and (C) 4 °C.
Figure 4.
Figure 4.
In vitro studies of MEL-NLC. (A) In vitro release profile of MEL-NLC vs. free MEL carried out for 48 h. (B) Adjustment to a two-phase decay model and one-phase decay model respectively. (C) Mean fluorescent intensity after 5, 15, 30 min and 1, 2 and 4 h in low (0.165 μg /ml) and high (0.825 μg/ml) concentration of compound in MV4-11 cells. (D) fluorescent intensity: histogram image from flow cytometry (for high concentration of compound): black line: unlabeled control; red line: after 5 min.; green line: after 15 min.; blue line: after 30 min.; light green line: after 1 h; yellow line: after 2 h; purple line: after 4 h.
Figure 5.
Figure 5.
Toxicity studies on chick chorioallantoic membrane at time 0 h and after 48 h post-instillation of the control (NaCl), a solution of MEL (Free MEL), and the nanoformulation (MEL-NLC).
See this image and copyright information in PMC

References

    1. Pilleron S, Sarfati D, Janssen-Heijnen M, et al. Global cancer incidence in older adults, 2012 and 2035: a population-based study. Int J Cancer. 2019;144:49–58. doi: 10.1002/IJC.31664 - DOI - PubMed
    1. Philip C, Mathew A, John MJ. Cancer care: challenges in the developing world. Cancer Res Stat Treat. 2018;1:58. doi: 10.4103/Crst.Crst_1_17 - DOI
    1. Gaidai O, Yan P, Xing Y. Future world cancer death rate prediction. Sci Rep. 2023;13:1–9. doi: 10.1038/s41598-023-27547-x - DOI - PMC - PubMed

    2. • Overview of world statitics regarding cancer and its impact.

    1. Wang X, Zhang H, Chen X. Drug resistance and combating drug resistance in cancer. Cancer Drug Resist. 2019;2:160. doi: 10.20517/CDR.2019.10 - DOI - PMC - PubMed
    1. Vasan N, Baselga J, Hyman DM. A view on drug resistance in cancer. Nature. 2019;575:299–309. doi: 10.1038/s41586-019-1730-1 - DOI - PMC - PubMed

Publication types

LinkOut - more resources