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Cellular and Non-cellular Antioxidant Properties of Vitamin E–Loaded Metallic-Quercetin/Polycaprolactone Nanoparticles for the Treatment of Melanogenesis

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Abstract

Inhibition of melanogenesis by quercetin and vitamin E is extensively reported in the literature, independently, with limitations in antioxidant potential owing to less permeation, solubility, decreased bioavailability, and reduced stability. Thus, the aim of the present study was to synthesize a novel complex of metal ions (copper and zinc) with quercetin to enhance antioxidant properties which were confirmed by docking studies. Polycaprolactone-based nanoparticles of the synthesized complex (PCL-NPs, Q-PCL-NPs, Zn-Q-PCL-NPs, Cu-Q-PCL-NPs) were made later loaded with vitamin E which made the study more interesting in enhancing antioxidant profile. Nanoparticles were characterized for zeta size, charge, and polydispersity index, while physiochemical analysis of nanoparticles was strengthened by FTIR. Cu-Q-PCL-NPs-E showed maximum in vitro release of vitamin E, i.e., 80 ± 0.54%. Non-cellular antioxidant effect by 2,2-diphenyl-1-picrylhydrazyl was observed at 93 ± 0.23% in Cu-Q-PCL-NPs-E which was twofold as compared to Zn-Q-PCL-NPs-E. Michigan Cancer Foundation-7 (MCF-7) cancer cell lines were used to investigate the anticancer and cellular antioxidant profile of loaded and unloaded nanoparticles. Results revealed reactive oxygen species activity of 90 ± 0.32% with the addition of 89 ± 0.64% of its anticancer behavior shown by Cu-Q-PCL-NPs-E after 6 and 24h. Similarly, 80 ± 0.53% inhibition of melanocyte cells and 95 ± 0.54% increase of keratinocyte cells were also shown by Cu-Q-PCL-NPs-E that confirmed the tyrosinase enzyme inhibitory effect. Conclusively, the use of zinc and copper complex in unloaded and vitamin E–loaded nanoparticles can provide enhanced antioxidant properties with inhibition of melanin, which can be used for treating diseases of melanogenesis.

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Acknowledgements

The authors are very much thankful to the Department of pharmaceutics and faculty of pharmacy, Bahauddin Zakariya University Multan, for providing the lab facilities.

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Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Multan, Pakistan

    Nasreen Ramzan, Muhammad Azeem, Fazal Rahman Sajid Chughtai, Muhammad Hanif, Nabeela Ameer & Muhammad Qaisar

  2. Institute of Chemical Science, Bahauddin Zakariya University Multan, Multan, Pakistan

    Nasreen Ramzan & Khalid Mahmood

  3. Hamdard Institute of Pharmaceutical Sciences, Hamdard University Islamabad Campus, Islamabad, Pakistan

    Muhammad Azeem

  4. Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan

    Shahid Shah

  5. Department of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Multan, Pakistan

    Zakia Bashir

  6. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bahauddin Zakariya University Multan, Multan, Pakistan

    Farhan Siddique

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  1. Nasreen Ramzan
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Contributions

Nasreen Ramzan: Researcher. Performed the experimental work in the laboratories of the department of pharmaceutics.

Muhammad Hanif: Mentor. Prepared the main idea and guidance for the fulfillment of the results.

Khalid Mahmood: Organic chemist. Worked on the graphical abstract, FTIR, and TLC.

Muhammad Azeem, Nabeela Ameer, Fazal Rahman Sajid Chugtai: Lab collaboration. Provided the help in application of the statistical, Microsoft Excel, and the document of the proposed research work.

Farhan Siddique: Conducted the computational analysis using DFT.

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Correspondence to Khalid Mahmood or Muhammad Hanif.

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Ramzan, N., Azeem, M., Mahmood, K. et al. Cellular and Non-cellular Antioxidant Properties of Vitamin E–Loaded Metallic-Quercetin/Polycaprolactone Nanoparticles for the Treatment of Melanogenesis. AAPS PharmSciTech 24, 141 (2023). https://doi.org/10.1208/s12249-023-02588-7

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