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Implications of Solid Lipid Nanoparticles of Ganoderic Acid for the Treatment and Management of Hepatocellular Carcinoma

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Abstract

Purpose

The present work describes the systematic development of ganoderic acid (GA)–loaded solid lipid nanoparticles (SLNs) for the treatment of hepatocellular carcinoma (HCC).

Methods

A full factorial design was employed for optimization of the GA-loaded SLNs prepared by hot-homogenization method, where Capmul MCMC10 and soy lecithin were used as solid lipid and surfactant, while poloxamer 188 was used as stabilizer. GA-SLNs were subjected to detailed in vitro and in vivo characterization studies.

Results

The optimized GA-SLNs exhibited particle size of 73 nm, entrapment efficiency of 66% and loading capacity of 11.53%. In vitro drug release study carried out by microdialysis bag method indicated more than 70% drug release was observed within the 8-h time period. In vitro cytotoxicity study of GA-SLNs performed on HepG2 cell line by MTT assay indicated that GA-SLNs exhibited comparatively higher cytotoxicity than GA solution and Blank SLNs. IC50 values of GA-SLNs and GA solution after 72 h exposure were found to be 25.1 μg/mL and 36.2 μg/mL, respectively. Moreover, particle size and amount of GA entrapped in SLNs exhibited nonsignificant difference over a 12-week storage period at 25 °C/75% RH. In vivo anticancer activity of GA-SLNs in male Wistar rats demonstrated significant reduction (P < 0.001) in the size of hepatic nodules and variation in the levels of oxidative stress in a dose-dependent manner.

Conclusions

Overall, GA-SLNs showed better chemoprotective effect over GA solution, thus construed superior efficacy of the developed nanoformulation for the treatment of HCC.

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Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences, Allahabad, UP, India

    Mahfoozur Rahman

  2. Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India

    Sarwar Beg

  3. Department of Pharmacology, College of Pharmacy, Jouf University, Sakakah, Saudi Arabia

    Khalid S. Alharbi & Muhammad Afzal

  4. Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakakah, Saudi Arabia

    Nabil K. Alruwaili

  5. Department of Clinical Pharmacy, College of Pharmacy, Jouf University, Sakakah, Saudi Arabia

    Nasser Hadal Alotaibi & Abdulaziz I. Alzarea

  6. Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia

    Waleed H. Almalki

  7. Department of Pharmacology and Toxicology, Unaizah College of Pharmacy, Qassim University, Qassim, Saudi Arabia

    Sattam Khulaif Alenezi

  8. Department of Pharmacy Practice, College of Pharmacy, Qassim University, Qassim, Saudi Arabia

    Waleed M. Altowayan

  9. Department of Pharmacy Practice, Unaizah College of Pharmacy, Qassim University, Qassim, Saudi Arabia

    Mohammed S. Alshammari

  10. Department of Pharmacology, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India

    Shakir Saleem

  11. Natural Product Drug Discovery Laboratory, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, UP, India

    Vikas Kumar

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  1. Mahfoozur Rahman
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Corresponding author

Correspondence to Vikas Kumar.

Ethics declarations

Experiments were conducted as per the guidelines issued by all the international guidances as well as the guidelines of Committee for Protection, Control and Supervision on Experimental Animals (CPCSEA), Govt. of India. The study protocol was approved by the Institutional Animal Ethical Committee (IAEC) of Siddhartha Institute of Pharmacy, Dehradun, India (Reg. No. SIP/IAEC/PCOL/06/2017). In addition, all laboratory parameters linked to animals were performed in accordance with the appropriate IAEC rules and laws.

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The authors declare that they have no conflict of interest.

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Rahman, M., Beg, S., Alharbi, K.S. et al. Implications of Solid Lipid Nanoparticles of Ganoderic Acid for the Treatment and Management of Hepatocellular Carcinoma. J Pharm Innov 16, 359–370 (2021). https://doi.org/10.1007/s12247-020-09450-4

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