Quality by Design Empowered Preparation of Itraconazole Albumin Nanoparticles for Prostate Cancer

Overview

Journal Drug Deliv Transl Res

Publisher Springer

Specialty Pharmacology

Date 2024 May 2

PMID 38696091

Authors

Saurabh Shah

Paras Famta

Anamika Sharma

Rahul Kumar

Giriraj Pandey

Ganesh Vambhurkar

Dadi A Srinivasarao

Akshay Shinde

Sajja Bhanu Prasad

Amit Asthana

Saurabh Srivastava

Affiliations

Soon will be listed here.

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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