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Entrapment and Delivery of Doxorubicin: Employing a Permeable Lipopeptide-Based Hydrogel as an Efficient Cationic Binder

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Abstract 

Lipopeptides have been the subject of great interest as vehicles for drug delivery, but the potential usage of their biological composites has not been extensively studied. Here, the extracellular lipopeptide composite (ELC) of a lipopeptide-producing bacterium was extracted and examined to deliver doxorubicin (DOX) as a cationic drug. MALDI-TOF mass spectrometry analysis on the lipopeptide moiety of ELC revealed that this hydrogel consists of 13 lipopeptide isomers. Furthermore, scanning electron microscope (SEM) studies showed that the permeability of ELC in acidic pH was significantly more than basic condition. In this study, 81% of DOX was successfully entrapped in ELC and the release of the drug was measured in acidic, neutral, and basic conditions. The results indicated that the release profile of the drug in acidic pH was about 10 and 16 fold more than neutral and basic conditions, respectively. Besides, the toxicity of DOX-conjugated ELC against PBMC cells was more than free DOX, suggesting the adequate drug release from ELC. Since the surrounding environment of tumor cells is often acidic, this pH-sensitive carrier could be a candidate for cancer therapy to improve the exposure of tumor cells to the drugs.

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References

  1. Yang, F., Chen, H., Liu, Y., Yin, K., Wang, Y., Li, X., Wang, G., Wang, S., Tan, X., & Xu, C. (2013). Cellular Physiology and Biochemistry., 32, 1072–1082.

    Article  CAS  PubMed  Google Scholar 

  2. Chen, H.-R., Sherr, D. H., Hu, Z., & DeLisi, C. (2016). A network-based approach to drug repositioning identifies plausible candidates for breast cancer and prostate cancer. BMC medical genomics, 9, 1–11.

    Article  CAS  Google Scholar 

  3. Bakkenist, C. J., Czambel, R. K., Hershberger, P. A., Tawbi, H., Beumer, J. H., & Schmitz, J. C. (2015). A quasi-quantitative dual multiplexed immunoblot method to simultaneously analyze ATM and H2AX Phosphorylation in human peripheral blood mononuclear cells. Oncoscience, 2, 542.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Szwed, M., Laroche-Clary, A., Robert, J., & Jozwiak, Z. (2016). Efficacy of doxorubicin-transferrin conjugate in apoptosis induction in human leukemia cells through reactive oxygen species generation. Cellular Oncology, 39, 107–118.

    Article  CAS  Google Scholar 

  5. Misra, R., & Sahoo, S. K. (2011). Coformulation of doxorubicin and curcumin in poly (D, L-lactide-co-glycolide) nanoparticles suppresses the development of multidrug resistance in K562 cells. Molecular pharmaceutics, 8, 852–866.

    Article  CAS  PubMed  Google Scholar 

  6. Kameda, Y., Ouhira, S., Matsui, K., & KANATOMO, S., HASE, T. and ATSUSAKA, T. (1974). Antitumor activity of Bacillus natto. V. Isolation and characterization of surfactin in the culture medium of Bacillus natto KMD 2311. Chemical and Pharmaceutical Bulletin, 22, 938–944.

    Article  CAS  PubMed  Google Scholar 

  7. Liu, X., Tao, X., Zou, A., Yang, S., Zhang, L., & Mu, B. (2010). Effect of themicrobial lipopeptide on tumor cell lines: Apoptosis induced by disturbing the fatty acid composition of cell membrane. Protein & cell, 1, 584–594.

    Article  CAS  Google Scholar 

  8. Sahnoun, R., Mnif, I., Fetoui, H., Gdoura, R., Chaabouni, K., Makni-Ayadi, F., Kallel, C., Ellouze-Chaabouni, S., & Ghribi, D. (2014). Evaluation of Bacillus subtilis SPB1 lipopeptide biosurfactant toxicity towards mice. International Journal of Peptide Research and Therapeutics, 20, 333–340.

    Article  CAS  Google Scholar 

  9. Hmidet, N., Ben Ayed, H., Jacques, P. and Nasri, M. (2017) Enhancement of surfactin and fengycin production by Bacillus mojavensis A21: Application for diesel biodegradation. BioMed research international, 2017.

  10. Ma, Z., Wang, N., Hu, J., & Wang, S. (2012). Isolation and characterization of a new iturinic lipopeptide, mojavensin A produced by a marine-derived bacterium Bacillus mojavensis B0621A. The Journal of antibiotics, 65, 317–322.

    Article  CAS  PubMed  Google Scholar 

  11. Zhao, H., Shao, D., Jiang, C., Shi, J., Li, Q., Huang, Q., Rajoka, M. S. R., Yang, H., & Jin, M. (2017). Biological activity of lipopeptides from Bacillus. Applied microbiology and biotechnology, 101, 5951–5960.

    Article  CAS  PubMed  Google Scholar 

  12. Kanna, R., Gummadi, S. N., & Kumar, G. S. (2014). Production and characterization of biosurfactant by Pseudomonas putida MTCC 2467. Journal of Biological Sciences, 14, 436.

    Article  CAS  Google Scholar 

  13. Fanaei, M., & Emtiazi, G. (2018). Microbial assisted (Bacillus mojavensis) production of bio-surfactant lipopeptide with potential pharmaceutical applications and its characterization by MALDI-TOF-MS analysis. Journal of Molecular Liquids, 268, 707–714.

    Article  CAS  Google Scholar 

  14. Fanaei, M., Jurcic, K., & Emtiazi, G. (2021). Detection of simultaneous production of kurstakin, fengycin and surfactin lipopeptides in Bacillus mojavensis using a novel gel-based method and MALDI-TOF spectrometry. World Journal of Microbiology and Biotechnology, 37, 1–11.

    Article  Google Scholar 

  15. Vanavil, B., Perumalsamy, M., & Rao, A. S. (2013). Biosurfactant production from novel air isolate NITT6L: Screening, characterization and optimization of media. Journal of microbiology and biotechnology, 23, 1229–1243.

    Article  CAS  PubMed  Google Scholar 

  16. Zhi, Y., Wu, Q., & Xu, Y. (2017). Genome and transcriptome analysis of surfactin biosynthesis in Bacillus amyloliquefaciens MT45. Scientific reports, 7, 1–13.

    Article  Google Scholar 

  17. Li, X., Zhang, Y., Wei, Z., Guan, Z., Cai, Y., & Liao, X. (2016). Antifungal activity of isolated Bacillus amyloliquefaciens SYBC H47 for the biocontrol of peach gummosis. PLoS One, 11, e0162125.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Hathout, Y., Ho, Y.-P., Ryzhov, V., Demirev, P., & Fenselau, C. (2000). Kurstakins: A new class of lipopeptides isolated from Bacillus thuringiensis. Journal of natural products, 63, 1492–1496.

    Article  CAS  PubMed  Google Scholar 

  19. Dimkić, I., Stanković, S., Nišavić, M., Petković, M., Ristivojević, P., Fira, D., & Berić, T. (2017). The profile and antimicrobial activity of Bacillus lipopeptide extracts of five potential biocontrol strains. Frontiers in microbiology, 8, 925.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Rizwan, M., Yahya, R., Hassan, A., Yar, M., Azzahari, A. D., Selvanathan, V., Sonsudin, F., & Abouloula, C. N. (2017). pH sensitive hydrogels in drug delivery: Brief history, properties, swelling, and release mechanism, material selection and applications. Polymers, 9, 137.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors wish to thank Ms. Kristina Jurcic (Department of Biochemistry, MALDI Mass Spectrometry Facility, The University of Western Ontario, Canada) for her help with MS spectroscopy analysis and interpretation.

Funding

The current study was supported by Grant from the University of Isfahan to Maryam Fanaei for obtaining Ph. D. degree.

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All authors contributed to the study’s conception and design. The first draft of the manuscript was written by Maryam Fanaei, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Giti Emtiazi.

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The approval of the National Committee on Ethics in Biomedical Research of the University of Isfahan was obtained.

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Fanaei, M., Emtiazi, G. Entrapment and Delivery of Doxorubicin: Employing a Permeable Lipopeptide-Based Hydrogel as an Efficient Cationic Binder. Appl Biochem Biotechnol 195, 3733–3746 (2023). https://doi.org/10.1007/s12010-022-04068-3

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