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Formulation and evaluation of rutin-loaded solid lipid nanoparticles for the treatment of brain tumor

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Abstract

The primary requirement for curing cancer is the delivery of essential drug load at the cancer microenvironment with therapeutic efficacy. Considering this, the present study aims to formulate “Rutin”-encapsulated solid lipid nanoparticles (SLNs) for effective brain delivery across the blood-brain barrier (BBB). Rutin-loaded SLNs were fabricated by oil-in-water microemulsion technique and were characterized for their physicochemical properties. The in vivo biodistribution study of rutin-loaded SLNs was studied using Rattus norvegicus rats. Subsequently, in silico molecular docking and dynamic calculations were performed to examine the binding affinity as well as stability of rutin at the active site of target protein “epidermal growth factor receptor (EGFR).” Formulated rutin-loaded SLNs were predominantly spherical in shape with an average particle diameter of 100 nm. Additionally, the biocompatibility and stability have been proved in vitro. The presence and biodistribution of rutin in vivo after 54 h of injection were observed as 15.23 ± 0.32% in the brain, 8.68 ± 0.63% in the heart, 4.78 ± 0.28% in the kidney, 5.04 ± 0.37% in the liver, 0.92 ± 0.04% in the lung, and 11.52 ± 0.65% in the spleen, respectively. Molecular docking results revealed the higher binding energy of − 150.973 kJ/mol of rutin with EGFR. Molecular dynamic simulation studies demonstrated that rutin with EGFR receptor complex was highly stable at 30 ns. The observed results exemplified that the formulated rutin-loaded SLNs were stable in circulation for a period up to 5 days. Thus, rutin-encapsulated SLN formulations can be used as a promising vector to target tumors across BBB.

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Acknowledgements

We thank Mr. P. Kathirvel, Mr. V. Krishnaprabhu Technicians for FT-IR and XRD analysis, and Sir CV Raman, KS Krishnan International Research Center, Kalasalingam Academy of Research and Education, Krishnankoil, Tamilnadu, India.

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Authors and Affiliations

  1. Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil, Tamilnadu, 626126, India

    Sureshbabu Ram Kumar Pandian & Selvaraj Kunjiappan

  2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, M S R Nagar, Bengaluru, Karnataka, 560054, India

    Parasuraman Pavadai & Lakshmi M. Sundar

  3. Department of Pharmaceutics, Arulmigu Kalasalingam College of Pharmacy, Krishnankoil, Tamilnadu, 626126, India

    Sivakumar Vellaisamy

  4. Department of Biotechnology, Mepco Schlenk Engineering College, Sivakasi, Tamilnadu, 626005, India

    Vigneshwaran Ravishankar

  5. School of Mechanical Engineering, Vellore Institute of Technology, Vellore, Tamilnadu, 632014, India

    Ponnusamy Palanisamy

  6. Department of Biotechnology, Siddaganga Institute of Technology, Tumakuru, Karnataka, 572103, India

    Vivek Chandramohan

  7. Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Rajasthan, 333031, India

    Murugesan Sankaranarayanan

  8. Department of Pharmaceutical Chemistry, Swamy Vivekananda College of Pharmacy, Elayampalayam, Namakkal, Tamilnadu, 637205, India

    Theivendren Panneerselvam

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  1. Sureshbabu Ram Kumar Pandian
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  2. Parasuraman Pavadai
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  3. Sivakumar Vellaisamy
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  5. Ponnusamy Palanisamy
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  6. Lakshmi M. Sundar
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  8. Murugesan Sankaranarayanan
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  9. Theivendren Panneerselvam
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  10. Selvaraj Kunjiappan
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Contributions

SRK, PP, SV, VR, PP, TP, MS, and SK conceived and designed the research. SRK, PP, SV, VR, PP, LMS, VC, TP, MS, and SK conducted the experiments. SRK, MS, TP, PP, and SK analyzed the data. KS, SRK, MS, and TP wrote the manuscript. All authors read and approved the manuscript. All data were generated in-house and no paper mill was used.

Corresponding authors

Correspondence to Murugesan Sankaranarayanan, Theivendren Panneerselvam or Selvaraj Kunjiappan.

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This article does not contain any studies with human participants performed by any of the authors. Further, all experimental procedures were performed in accordance with the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals and were approved by the local animal protection committee.

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Pandian, S.R.K., Pavadai, P., Vellaisamy, S. et al. Formulation and evaluation of rutin-loaded solid lipid nanoparticles for the treatment of brain tumor. Naunyn-Schmiedeberg's Arch Pharmacol 394, 735–749 (2021). https://doi.org/10.1007/s00210-020-02015-9

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