Quality by design enabled formulation development of regorafenib monohydrate loaded PEGylated PLGA polymeric nanoparticles: Enhanced oral bioavailability and biopharmaceutical attributes

Document Type : Research Paper

Authors

1 School of Pharmaceutical Sciences (SPS), Siksha O Anusandhan Deemed to be University, Kalinga Nagar, Ghatikia, Bhubaneswar-751029, Odisha, India

2 Amity Institute of Pharmacy, Amity University, Major Arterial Road, AA II, Newtown, Kadampukur, Kolkata-700135, West Bengal, India

3 Department of Pharmaceutics, Roland Institute of Pharmaceutical Sciences, Berhampur-760010, Odisha, India

4 School of Pharmacy and Life Science, Centurion University of Technology and Management Bhubaneswar-751009, Odisha, India

Abstract

Objective(s): Using a quality-by-design methodology, the current research is aimed to prepare and enhance the PEGylated PLGA-loaded regorafenib monohydrate polymeric nanoparticles for enhancing oral bioavailability and biopharmaceutical attributes. The oral multi-kinase inhibitor inhibits VEGFR2-TIE2 tyrosine kinases on two separate targets, which results in anti-angiogenic activity. It also inhibits stromal and oncogenic receptor tyrosine kinases. 
Materials and Methods: The current study developed nanosized, biocompatible, and PEGylated PLGA polymeric nanoparticles to administer regorafenib monohydrate to patients with metastatic colon cancer. This was accomplished using a modified nanoprecipitation technique to make drug-encapsulated PEGylated PLGA nanoparticles with poloxamer 188 as a stabilizer. 
Results: The polymeric nanoformulations were characterized for zeta potential, distribution of particle size, entrapment efficiency, DSC, FT-IR, X-RD, and SEM. Both in vitro and in vivo experimental studies were performed for the pure drug and the improved nanoparticle formulation.
Conclusion: The nanoparticles obtained from optimization studies  were found to have smaller particle sizes, higher entrapment efficiency (%), drug loading capacity, spherical shape particles, amorphous drug embedded matrix, and a biphasic delayed release pattern. These findings suggest that drug-loaded PEGylated PLGA nanoparticles are a potent formulation for the treatment of colon cancer, with improved oral bioavailability and biopharmaceutical properties.

Keywords

References

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Nanomedicine Journal
Volume 11, Issue 4
October 2024
Pages 401-416

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