Skip to main content
Log in

Caffeic Acid Loaded Lipid Polymer Hybrid Nanoparticles: Ex Vivo and Pre-clinical Evaluation Against Liver Cirrhosis

  • Original Paper
  • Published:
Journal of Cluster Science Aims and scope Submit manuscript

Abstract

This study describes the development and characterization of caffeic acid (CA)-loaded lipid polymer hybrid nanoparticles (LPHNPs) for treating liver cirrhosis. The developed CA-loaded LPHNPs showed particle size of 150.9 nm, zeta potential of − 0.660 mV, and entrapment efficiency of 95.12%. The photomicrograph and TEM images revealed a dense spherical shape of optimized aforementioned formulation. The in vitro drug release studies revealed cumulative CA release of 82.46% at the end of 80 h, while Korsemeyer-Peppas model was found to be best fitted (n < 0.45). Further, the stability testing at 25ºC/60%RH revealed stable nanoparticles formulation with particle size homogeneity up to 12 weeks. Pharmacokinetic data revealed 6.1-fold higher bioavailability of CA-LPHNPs as compared to that of CA suspension. The biodistribution profile of CA-LPHNPs revealed higher concentrations in liver > spleen > kidney > heart > lung over the CA suspension. The CA-loaded LPHNPs found a reduction of hepatic enzymes including ALT, AST and ALP to the value quite close to the normal control group of rats. On the other side, the administration of CA-loaded LPHNPs resulted in normalization of the antioxidant value and reduced proinflammatory cytokines close to the normal control group of rats over the PCM induced liver cirrhosis group in rats. It was further established by histopathology of the liver microtome sections that the therapy affected liver cirrhosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Data Availability

The authors confirm that the data supporting the findings of this study are available within the articles and can share upon request.

References

  1. E. Scarpellini, C. Luigiano, G. Svegliati-Baroni, D. Dumitrascu, T. Larussa, V. Santori, F. Luzza, and L. Abenavoli (2020). Liver cirrhosis complications management at the emergency department. Rev. Recent. Clin. Trials. 15 (4), 331–338.

    Article  PubMed  Google Scholar 

  2. T. Akahane, H. Yoshiji, N. Shokakibyo, and G. Zasshi (2021). Pathophysiology and diagnosis of liver cirrhosis. Nihon. Shokakibyo. Gakkai. Zasshi. 118 (1), 14–21.

    PubMed  Google Scholar 

  3. N. Yang, S. Dang, J. Shi, F. Wu, M. Li, X. Zhang, Y. Li, X. Jia, and S. Zhai (2017). Caffeic acid phenethyl ester attenuates liver fibrosis via inhibition of TGF-beta1/Smad3 pathway and induction of autophagy pathway. Biochem. Biophys. Res. Commun. 486 (1), 22–28.

    Article  CAS  PubMed  Google Scholar 

  4. H. Miao, Y. Zhang, Z. Huang, B. Lu, and L. Ji (2019). Lonicera japonica attenuates carbon tetrachloride-induced liver fibrosis in mice: molecular mechanisms of action. Am. J. Chin. Med. 47 (2), 351–367.

    Article  CAS  PubMed  Google Scholar 

  5. G. M. Sulaiman, A. A. Al-Amiery, and R. Bagnati (2014). Theoretical, antioxidant and cytotoxic activities of caffeic acid phenethyl ester and chrysin. Int. J. Food. Sci. Nutr. 65 (1), 101–105.

    Article  CAS  PubMed  Google Scholar 

  6. Y. Z. Zheng, G. Deng, R. Guo, Z. M. Fu, and D. F. Chen (2020). Effects of different ester chains on the antioxidant activity of caffeic acid. Bioorg. Chem. 105, 104341.

    Article  CAS  PubMed  Google Scholar 

  7. E. M. Abdou, M. A. A. Fayed, D. Helal, and K. A. Ahmed (2019). Assessment of the hepatoprotective effect of developed lipid-polymer hybrid nanoparticles (LPHNPs) encapsulating naturally extracted beta-Sitosterol against CCl4 induced hepatotoxicity in rats. Sci. Rep. 9 (1), 19779.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. R. Hassan, S. N. Tammam, S. E. Safy, M. Abdel-Halim, A. Asimakopoulou, R. Weiskirchen, and S. Mansour (2019). Prevention of hepatic stellate cell activation using JQ1- and atorvastatin-loaded chitosan nanoparticles as a therapy of liver fibrosis. Eur. J. Pharm. Biopharm. 134, 96–106.

    Article  CAS  PubMed  Google Scholar 

  9. A. Mukherjee, A. K. Waters, P. Kalyan, A. S. Achrol, S. Kesari, and V. M. Yenugonda (2019). Lipid-polymer hybrid nanoparticles as a next-generation drug delivery platform: state of the art, emerging technologies, and perspectives. Int. J. Nanomed. 14, 1937–1952.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. J. M. P. J. Garrido, A. S. Cerqueira, D. Chavarria, T. Silva, F. Borges, and Garrido, (2018). Microencapsulation of caffeic acid phenethyl ester and caffeic acid phenethyl amide by inclusion in hydroxypropyl-beta-cyclodextrin. Food. Chem. 254, 260–265.

    Article  CAS  PubMed  Google Scholar 

  11. M. M. Khan, A. Madni, V. Torchilin, N. Filipczak, J. Pan, N. Tahir, and H. Shah (2019). Lipid-chitosan hybrid nanoparticles for controlled delivery of cisplatin. Drug. Deliv. 26 (1), 765–772.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. S. Godara, V. Lather, S. V. Kirthanashri, R. Awasthi, and D. Pandita (2020). Lipid-PLGA hybrid nanoparticles of paclitaxel: Preparation, characterization, in vitro and in vivo evaluation. Mater. Sci. Eng. C. 109, 110576.

    Article  CAS  PubMed  Google Scholar 

  13. S. Li, Z. Xu, M. Alrobaian, O. Afzal, I. Kazmi, W. H. Almalki, A. S. A. Altamimi, F. A. Al-Abbasi, K. S. Alharbi, W. M. Altowayan, T. Singh, M. H. Akhter, M. Gupta, M. Rahman, and S. Beg (2021). EGF-functionalized lipid-polymer hybrid nanoparticles of 5-fluorouracil and sulforaphane with enhanced bioavailability and anticancer activity against colon carcinoma. Biotechnol. Appl. Biochem. https://doi.org/10.1002/bab.2279.

    Article  PubMed  PubMed Central  Google Scholar 

  14. M. Rahman, W. H. Almalki, O. Afzal, A. S. Alfawaz Altamimi, I. Kazmi, F. A. Al-Abbasi, H. Choudhry, S. K. Alenezi, M. A. Barkat, S. Beg, V. Kumar, and A. Alhalmi (2020). Cationic solid lipid nanoparticles of resveratrol for hepatocellular carcinoma treatment: systematic optimization, in vitro characterization and preclinical investigation. Int. J. Nanomedicine. 15, 9283–9299.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. B. Wang, L. Sun, M. Wen, Y. Tan, W. H. Almalki, H. Katouah, I. Kazmi, O. Afzal, A. S. A. Altamimi, F. A. Al-Abbasi, M. Alrobaian, K. S. Alharbi, S. K. Alenezi, A. F. Alghaith, S. Beg, and M. Rahman (2021). Nano lipidic carriers for codelivery of sorafenib and ganoderic acid for enhanced synergistic antitumor efficacy against hepatocellular carcinoma. Saudi. Pharm. J. 29 (8), 843–856.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. L. Li, H. Wang, Z. Y. Ong, K. Xu, P. L. RachelEe, S. Zheng, J. L. Hedrick, and Y. Y. Yang (2010). Polymer- and lipid-based nanoparticle therapeutics for the treatment of liver diseases. Nano Today 5 (4), 296–312.

    Article  CAS  Google Scholar 

  17. A. Singh, I. Ahmad, S. Akhter, G. K. Jain, Z. Iqbal, S. Talegaonkar, and F. J. Ahmad (2013). Nanocarrier based formulation of Thymoquinone improves oral delivery: stability assessment, in vitro and in vivo studies. Colloids. Surf. B. 102, 822–832.

    Article  CAS  PubMed  Google Scholar 

  18. G. Biancofiore, L. Bindi, M. Miccoli, M. R. Metelli, E. Panicucci, A. Baggiani, and F. Filipponi (2013). Balanceof pro-and anti-inflammatory cytokines in cirrhotic patients undergoing liver transplantation. Transpl. Immunol. 28 (4), 193–197.

    Article  CAS  PubMed  Google Scholar 

  19. S. N. F. Zaidi and T. Mahboob (2017). Prevention of liver cirrhosis by Silymarin. Pak. J. Pharm. Sci. 30 (4), 1203–1211.

    CAS  PubMed  Google Scholar 

  20. F. Meng, K. Wang, T. Aoyama, S. I. Grivennikov, Y. Paik, D. Scholten, M. Cong, K. Iwaisako, X. Liu, M. Zhang, C. H. Österreicher, F. Stickel, K. Ley, D. A. Brenner, and T. Kisseleva (2012). Interleukin-17 signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice. Gastroenterology. 143 (3), 765–776.

    Article  CAS  PubMed  Google Scholar 

  21. H. M. Mansour, A. A. A. Salama, R. M. Abdel-Salam, N. A. Ahmed, N. N. Yassen, and H. F. Zaki (2018). The anti-inflammatory and anti-fibrotic effects of tadalafil in thioacetamide-induced liver fibrosis in rats. Can. J. Physiol. Pharmacol. 96 (12), 1308–1317.

    Article  PubMed  Google Scholar 

  22. B. Gao (2012). Disease. Gastroenterol. Hepatol. Suppl 2 (Suppl 2), 89–93.

    Article  Google Scholar 

  23. E. M. Brunt (2009). Histopathology of non-alcoholic fatty liver disease. Clin. Liver. Dis. 13 (4), 533–544.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the support provided by Taif University Researchers Supporting Project Number (TURSP-2020/33), Taif University, Saudi Arabia.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mahfoozur Rahman.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ansari, M.J., Rahman, M., Alrobaian, M. et al. Caffeic Acid Loaded Lipid Polymer Hybrid Nanoparticles: Ex Vivo and Pre-clinical Evaluation Against Liver Cirrhosis. J Clust Sci 34, 1757–1768 (2023). https://doi.org/10.1007/s10876-022-02283-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10876-022-02283-w

Keywords

Navigation