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Quality by design empowered preparation of itraconazole albumin nanoparticles for prostate cancer

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Abstract

The current advent explores the potential of itraconazole (ITR) in prostate cancer (PCa), by its incorporation into albumin nanoparticles (NP). ITR as a repurposed moiety has displayed tremendous potential in various cancers. However, poor aqueous solubility poses hurdles towards its clinical translation. Amorphisation of ITR was observed post-incorporation within NP matrix which could prevent its precipitation in aqueous media. ITR NP was developed using quality by design and multivariate analysis and evaluated for cellular uptake, cell proliferation inhibition and the mechanism of PCa cell inhibition. Time and concentration-dependent serum stability and hemolytic potential revealed safety of ITR NP. Morphological changes and nuclear staining studies revealed the efficacy of ITR and ITR NP in promoting growth inhibition of PC-3 cells. Superior qualitative and quantitative uptake, reactive oxygen species (ROS) and mitochondrial impairment for ITR NP in comparison with ITR and control group was observed. Cell cycle study revealed remarkable G2/M phase inhibition in PC-3 cells. ITR NP demonstrated superior anticancer potential in 3D tumoroids mimicking the micro-metastatic lesions compared to control and ITR. Hence, ITR NP can be a favorable alternative therapeutic alternative in PCa.

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Acknowledgements

The authors acknowledge the research funding support by the Department of Pharmaceuticals (DoP), Ministry of Chemicals and Fertilizers, Govt. of India to “Pharmaceutical Innovation and Translational Research Lab” (PITRL), Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER) Hyderabad, INDIA.

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Authors and Affiliations

  1. Pharmaceutical Innovation and Translational Research Laboratory (PITRL), Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad-500037, Hyderabad, India

    Saurabh Shah, Paras Famta, Giriraj Pandey, Ganesh Vambhurkar, Dadi A. Srinivasarao, Akshay Shinde, Sajja Bhanu Prasad & Saurabh Srivastava

  2. Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India

    Anamika Sharma & Rahul Kumar

  3. Department of Medical Devices, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India

    Amit Asthana

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  1. Saurabh Shah
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Contributions

Saurabh Shah—Conceptualization, Methodology, experimentation, software validation, Original draft writing; Paras Famta – Methodology, experimentation, software validation, Original draft writing; Anamika Sharma, Rahul Kumar, Giriraj Pandey, Ganesh Vambhurkar – Data curation, formal analysis; Dadi A. Srinivasarao, Akshay Shinde, Sajja Bhanu Prasad – Manuscript review editing; Amit Asthana—Supervision, and Saurabh Srivastava – Conceptualization, Supervision, Validation.

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Correspondence to Saurabh Srivastava.

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Shah, S., Famta, P., Sharma, A. et al. Quality by design empowered preparation of itraconazole albumin nanoparticles for prostate cancer. Drug Deliv. and Transl. Res. (2024). https://doi.org/10.1007/s13346-024-01592-z

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