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A Computational Approach for Exploring Indinavir as a Potent Protease Inhibitor and Development of Its Microsphere for Anticancer Activity

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Abstract

Purpose

The objective of the present investigation was to establish a molecular association of different proteases as cancer targets with the indinavir and how the physicochemical characteristics of the indinavir sulfate microsphere vary with different process variables was systemically established.

Methods

Molecular interactions with indinavir were identified and established by molecular simulation docking studies. Indinavir sulfate-loaded microspheres were prepared by the oil-in-oil emulsion solvent evaporation technique.

Results

Results indicated that indinavir could interact with all four proteases at the active binding site of receptors. Indinavir was found to show significantly higher interaction with Matrix Metalloproteases, Aspartate Proteases, and Cysteine Proteases with a binding energy of -8.80, -8.19, and -6.87, respectively, as compared to their native ligand. However, serine proteases exhibit less but significant interaction with a binding energy of -5.92 than the native ligand. The microspheres exhibited 72%-93% of entrapment and prolonged drug release (DR), up to 9 h. The drug-loaded microspheres showed invariable character by the Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and thermographs and revealed no drug-polymer interactions. The decrease in the drug's crystallinity was observed in X-ray diffraction (XRD). The scanning electron microscope (SEM) study revealed the spherical and porous nature of microspheres.

Conclusion

Indinavir could act as a potential inhibitor of different proteases associated with tumor growth initiation, progression, and metastasis, and microspheres with sustained DR could be utilized to deliver an anticancer drug in a more targeted way as an emerging cancer microsphere technology.

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Acknowledgements

The authors are thankful to Cipla, Ltd, Mumbai, India, for providing indinavir sulfate. Furthermore, the writers are obliged to Indian Institute of Technology (IIT), Kharagpur, India, University Science of Instrumental Centre (USIC), Jadavpur, Kolkata, India, Kanak Manjari Institute of Pharmaceutical Sciences Raurkela, Odisha, India, and University Department of Pharmaceutical Sciences and Utkal University, Bhubaneswar, Odisha, India for support in carrying out characterization studies.

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Authors and Affiliations

  1. Moradabad Educational Trust Group of Institutions, Faculty of Pharmacy, Moradabad, Uttar Pradesh, India

    Prasanta Kumar Mohapatra & Rajnish Srivastava

  2. Moradabad Institute of Technology (MIT) College of Pharmacy, Moradabad, Uttar Pradesh, India

    Krishna Kumar Varshney

  3. University Department of Pharmaceutical Sciences, Utkal University, Bhubaneswar, Odisha, India

    Sunit Kumar Sahoo

  4. Kanak Manjari Institute of Pharmaceutical Sciences, Rourkela, Odisha, India

    Asha Kesari

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  1. Prasanta Kumar Mohapatra
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  2. Rajnish Srivastava
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  3. Krishna Kumar Varshney
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  4. Sunit Kumar Sahoo
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  5. Asha Kesari
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Correspondence to Prasanta Kumar Mohapatra.

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The protocol was approved by the Institutional Animal Ethics Committee (IEAC) of the Post Graduate Department of Zoology, Utkal University, Vani Vihar, Bhubaneswar-751004, Orissa, India.

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No humans were used for studies that is the basis of this research. The whole protocol and procedures involving laboratory animals are strictly in compliance with the guidelines of the Committee for Control and Supervision of Experiments on Animals (CPCSEA), a statutory Committee, which is established under Chapter 4, Sect. 15(1) of the Prevention of Cruelty to Animals Act 1960.

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Mohapatra, P.K., Srivastava, R., Varshney, K.K. et al. A Computational Approach for Exploring Indinavir as a Potent Protease Inhibitor and Development of Its Microsphere for Anticancer Activity. J Pharm Innov 18, 1838–1869 (2023). https://doi.org/10.1007/s12247-023-09747-0

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