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Development of core–shell structured nanoparticle for sequential release of tariquidar and docetaxel to overcome multi drug-resistant cancer

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Abstract

Purpose

We developed a core–shell (CS) nanoparticle, docetaxel (DTX)-loaded core and tariquidar (TRQ)-loaded shell conjugated with PEG and RIPL peptide (D/C-T/S-PR), which sequentially releases TRQ and DTX to overcome multidrug resistant (MDR) cancer.

Methods

D/C-T/S-PR was fabricated by two-step method, including the formation of a DTX-loaded nanostructured lipid carrier (D/NLC) core by solvent emulsification-evaporation and a TRQ-loaded lipid bilayer shell using a film hydration method. CSs with a lipid mass ratio of shell to core from 1 to 5 (CS1–CS5) were prepared and purified by sucrose density gradient centrifugation. The physicochemical properties of the CSs were evaluated to select an optimal ratio. Additionally, CS formation was confirmed by transmission microscopy (TEM) and confocal laser scanning microscope (CLSM) images. In vitro drug release was evaluated and in vitro cellular uptake and cytotoxicity were assessed against MCF7 and MCF7/ADR cells.

Results

The amounts of CSs acquired after purification were increased with increasing lipid ratio. CS3 was selected as the final formulation due to its high drug loading. Using TEM, we observed the distinct formation of the shell coating the core in the D/C-T/S-PR, while CLSM was used to confirm the co-loading of two fluorescent probes in different layers. D/C-T/S-PR showed a burst release of TRQ from the shell, followed by sustained release of DTX from the core. D/C-T/S-PR showed enhanced uptake and cytotoxicity in both cell types.

Conclusion

We successfully developed a CS exhibiting sequential release of TRQ and DTX, which may represent a promising strategy to overcome MDR.

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Acknowledgements

This study was funded by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2022R1A2B5B02001794). This research was supported by CAU GPF Program through the Chung-Ang University in 2023 funded by BrainKorea21 Four. We also thank Prof. Dr. Kyung Hoon Min (College of Pharmacy, Chung-Ang University, Seoul, Korea) for kindly providing the MCF7/ADR cells for this study.

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Author notes

  1. Hyun Min Jung and Chang Hyun Kim have contributed equally to this work.

Authors and Affiliations

  1. College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul, 06974, Republic of Korea

    Hyun Min Jung, Chang Hyun Kim, Jo-Eun Seo, Yoon Tae Goo, Sun Ho Hong, Sangkil Lee & Young Wook Choi

  2. Department of Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, TX, 76107, USA

    Chang Hyun Kim

  3. College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam, 31116, Republic of Korea

    Myung Joo Kang

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Correspondence to Sangkil Lee or Young Wook Choi.

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All authors (H.M. Jung, C.H. Kim, J.E. Seo, Y.T Goo, S.H. Hong, M.J. Kang, S. Lee, and Y.W. Choi) declare that they have no conflicts of interest.

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Jung, H.M., Kim, C.H., Seo, JE. et al. Development of core–shell structured nanoparticle for sequential release of tariquidar and docetaxel to overcome multi drug-resistant cancer. J. Pharm. Investig. 54, 61–75 (2024). https://doi.org/10.1007/s40005-023-00645-8

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