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

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. Graphical Abstract