Design and manufacturing of novel smart pegylated nano-liposome co-encapsulating two herbal compounds: Silibinin and Glycyrrhizic acid with HAb18 monoclonal antibody for targeted co-delivery to liver cancer cells

Articles in Press

Document Type : Research Paper

Authors

1 Assistant professor of the Department of Nano biotechnology & Biomimetic, School of Life Science Engineering, College of Interdisciplinary Science and Technology, University of Tehran, Tehran, Iran

2 Department of Nano Biotechnology, Research Center for New Technologies In Life Science Engineering, University of Tehran, Tehran, Iran

3 Department of Nano Biotechnology, Research Center for New Technologies In Life Science Engineering, University of Tehran, Tehran, Iran 3.Department of Chemical Engineering, School of Engineering, University of Tehran, Tehran, Iran.

4 Department of Chemical Engineering, School of Engineering, University of Tehran, Tehran, Iran

5 School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

6 Department of Nano Biotechnology, Research Center for New Technologies In Life Science Engineering, University of Tehran, Tehran, Iran5.Pasteur Institute of Iran (IPI), Tehran, Iran.

7 Pasteur Institute of Iran (IPI), Tehran, Iran

8 Department of Nano biotechnology & Biomimetic, School of Life Science Engineering, College of Interdisciplinary Science and Technology, University of Tehran, Tehran, Iran

Abstract

Objective(s): Herbal nano-liposomes, also referred to as nano-Phytosomes, are formed through hydrogen bonding interactions between the phospholipids of lipid membranes and phytomolecules. This structure enhances the delivery efficiency of therapeutic agents. This study focuses on the use of PEGylated nano-liposomes co-loaded with two anti-cancer compounds derived from herbs, silibinin and glycyrrhizic acid, to target liver cancer cells.
Materials and Methods: The co-encapsulated nanoscale liposomes were synthesized using the thin-layer film hydration method with HEPES buffer, followed by sonication. The vesicles encapsulating silibinin and glycyrrhizic acid consisted of DPPC, cholesterol, and DSPE-mPEG2000 in a molar percentage ratio of approximately 61.5:35:3.5. A fluorescent label (DIL) was incorporated into the lipid bilayer at a concentration of 0.1 mol%. The multilamellar vesicles were then sonicated and filtered to produce the nano-liposomes. To enhance targeting, these co-encapsulated the nano-liposomes were conjugated with the monoclonal antibody HAb18. The resulting PEGylated nano-liposome formulation demonstrated a narrow size distribution, with an average particle diameter of approximately 45 nm. The zeta potential of the co-encapsulated nano-Phytosome was measured at -23.25mV. The encapsulation efficiencies of silibinin and glycyrrhizic acid were approximately 24.37% and 68.78%, respectively.
Results: The study revealed that the mean diameter of the nano-Phytosome increased upon targeting. Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM) images confirmed that the average diameters of the targeted co-encapsulated nano-liposomes were approximately 84 nm and 81 nm, respectively, while the monoclonal antibody HAb18 exhibited an average diameter of around 16.1 nm and 15 nm.
Conclusion: This targeted nano-system offers efficient delivery of herbal drugs to liver cancer cells.

Keywords

References

  1. Jin C, Yang W, Bai L, Wang J, Dou K. Preparation and characterization of targeted DOX-PLGA-PEG micelles decorated with bivalent fragment HAb18 F (ab') 2 for treatment of hepatocellular carcinoma. Journal of controlled release: official journal of the Controlled Release Society. 2011; 152: e14-e15.
  2. Cheng WW, Allen TM. Targeted delivery of anti-CD19 liposomal doxorubicin in B-cell lymphoma: a comparison of whole monoclonal antibody, Fab′ fragments and single chain Fv. Journal of Controlled Release. 2008; 126(1): 50-58.
  3. Woodle MC, Lasic DD. Sterically stabilized liposomes. Biochimica et biophysica acta (BBA)-reviews on biomembranes. 1992; 1113(2): 171-199.
  4. Rathore P, Swami G. Planterosomes: A potential phyto-phospholipid carriers for the bioavailability enhancement of herbal extracts. International Journal of pharmaceutical sciences and research. 2012; 3(3): 737.
  5. Post-White J, Ladas EJ, Kelly KM. Advances in the use of milk thistle (Silybum marianum). Integrative cancer therapies. 2007; 6(2): 104-109.
  6. Barzaghi N, Crema F, Gatti G, Pifferi G, Perucca E. Pharmacokinetic studies on IdB 1016, a silybin-phosphatidylcholine complex, in healthy human subjects. European journal of drug metabolism and pharmacokinetics. 1990; 15: 333-338.
  7. Schandalik R, Gatti G, Perucca E. Pharmacokinetics of silybin in bile following administration of silipide and silymarin in cholecystectomy patients. Arzneimittel-forschung. 1992; 42(7): 964-968.
  8. Burgess CA. Silybum marianum (milk thistle). 2003.
  9. Ramakrishnan G, Raghavendran HRB, Vinodhkumar R, Devaki T. Suppression of N-nitrosodiethylamine induced hepatocarcinogenesis by silymarin in rats. Chemico-biological interactions. 2006; 161(2): 104-114.
  10. Kaur M, Agarwal R. Silymarin and epithelial cancer chemoprevention: how close we are to bedside? Toxicology and applied pharmacology. 2007; 224(3): 350-359.
  11. Song Y, Zhuang J, Guo J, Xiao Y, Ping Q. Preparation and properties of a silybin-phospholipid complex. Die Pharmazie-An International Journal of Pharmaceutical Sciences. 2008; 63(1): 35-42.
  12. Gažák R, Marhol P, Purchartová K, Monti D, Biedermann D, Riva S, et al. Large-scale separation of silybin diastereoisomers using lipases. Process Biochemistry. 2010; 45(10): 1657-1663.
  13. Chen M-W, Tan W, Wang S-P, Zhong Z-F, Wang Y-T. Advances in the nanoparticle drug delivery systems of silymarin. Journal of Chinese Pharmaceutical Sciences. 2011; 20(5): 442.
  14. Tyagi AK, Singh RP, Agarwal C, Chan DC, Agarwal R. Silibinin strongly synergizes human prostate carcinoma DU145 cells to doxorubicin-induced growth Inhibition, G2-M arrest, and apoptosis. Clinical cancer research. 2002; 8(11): 3512-3519.
  15. Iden DL, Allen TM. In vitro and in vivo comparison of immunoliposomes made by conventional coupling techniques with those made by a new post-insertion approach. Biochimica et Biophysica Acta (BBA)-Biomembranes. 2001; 1513(2): 207-216.
  16. El-Samaligy M, Afifi N, Mahmoud E. Increasing bioavailability of silymarin using a buccal liposomal delivery system: preparation and experimental design investigation. International journal of pharmaceutics. 2006; 308(1-2): 140-148.
  17. Ochi MM, Amoabediny G, Rezayat SM, Akbarzadeh A, Ebrahimi B. In vitro co-delivery evaluation of novel pegylated nano-liposomal herbal drugs of silibinin and glycyrrhizic acid (nano-phytosome) to hepatocellular carcinoma cells. Cell Journal (Yakhteh). 2016; 18(2): 135.
  18. Archakov AI, Guseva MK, Uchaikin VF, Tikhonova EG, Ipatova OM. Medicinal forms of phospholipid preparations and methods for their preparation. Google Patents 2014.
  19. Amoabediny G, Ochi MM, Rezayat SM, Akbarzadeh A, Ebrahimi B. Targeted nano-liposome co-entrapping anti-cancer drugs. Google Patents 2018.
  20. Chu SC, Chiou HL, Chen PN, Yang SF, Hsieh YS. Silibinin inhibits the invasion of human lung cancer cells via decreased productions of urokinase‐plasminogen activator and matrix metalloproteinase‐2. Molecular Carcinogenesis: Published in cooperation with the University of Texas MD Anderson Cancer Center. 2004; 40(3): 143-149.
  21. Moreland N, La Grange L, Montoya R. Impact of in utero exposure to EtOH on corpus callosum development and paw preference in rats: protective effects of silymarin. BMC complementary and alternative medicine. 2002; 2: 1-6.
  22. Agarwal R, Agarwal C, Ichikawa H, Singh RP, Aggarwal BB. Anticancer potential of silymarin: from bench to bed side. Anticancer research. 2006; 26(6B): 4457-4498.
  23. Xu J, Xu H-Y, Zhang Q, Song F, Jiang J-L, Yang X-M, et al. HAb18G/CD147 functions in invasion and metastasis of hepatocellular carcinoma. Molecular cancer research. 2007; 5(6): 605-614.
  24. Moreira JN, Ishida T, Gaspar R, Allen TM. Use of the post-insertion technique to insert peptide ligands into pre-formed stealth liposomes with retention of binding activity and cytotoxicity. Pharmaceutical research. 2002; 19: 265-269.
  25. Bian A-N, Gao Y-H, Tan K-B, Liu P, Zeng G-J, Zhang X, et al. Preparation of human hepatocellular carcinoma-targeted liposome microbubbles and their immunological properties. World Journal of Gastroenterology: WJG. 2004; 10(23): 3424.
  26. San Paulo A, García R. High-resolution imaging of antibodies by tapping-mode atomic force microscopy: attractive and repulsive tip-sample interaction regimes. Biophysical Journal. 2000; 78(3): 1599-1605.
  27. Saber R, Sarkar S, Gill P, Nazari B, Faridani F. High resolution imaging of IgG and IgM molecules by scanning tunneling microscopy in air condition. Scientia Iranica. 2011; 18(6): 1643-1646.

 

Nanomedicine Journal

Articles in Press, Accepted Manuscript
Available Online from 26 July 2025

Files

Share

How to cite

Statistics