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

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-TIE...

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Main Authors: Dhananjay Panigrahi, Suryakanta Swain, Pratap Sahu, Debashish Ghose, Bikash Ranjan Jena
Format: Article
Language:English
Published: Mashhad University of Medical Sciences 2024-10-01
Series:Nanomedicine Journal
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Online Access:https://nmj.mums.ac.ir/article_24729_285ef57c987090066db90e2add2fc123.pdf
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author Dhananjay Panigrahi
Suryakanta Swain
Pratap Sahu
Debashish Ghose
Bikash Ranjan Jena
author_facet Dhananjay Panigrahi
Suryakanta Swain
Pratap Sahu
Debashish Ghose
Bikash Ranjan Jena
author_sort Dhananjay Panigrahi
collection DOAJ
description 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.
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spelling doaj-art-e3da27e1845b4146b887eaf224a841ef2025-08-20T03:31:51ZengMashhad University of Medical SciencesNanomedicine Journal2322-30492322-59042024-10-0111440141610.22038/nmj.2024.76842.186724729Quality by design enabled formulation development of regorafenib monohydrate loaded PEGylated PLGA polymeric nanoparticles: Enhanced oral bioavailability and biopharmaceutical attributesDhananjay Panigrahi0Suryakanta Swain1Pratap Sahu2Debashish Ghose3Bikash Ranjan Jena4School of Pharmaceutical Sciences (SPS), Siksha O Anusandhan Deemed to be University, Kalinga Nagar, Ghatikia, Bhubaneswar-751029, Odisha, IndiaAmity Institute of Pharmacy, Amity University, Major Arterial Road, AA II, Newtown, Kadampukur, Kolkata-700135, West Bengal, IndiaSchool of Pharmaceutical Sciences (SPS), Siksha O Anusandhan Deemed to be University, Kalinga Nagar, Ghatikia, Bhubaneswar-751029, Odisha, IndiaDepartment of Pharmaceutics, Roland Institute of Pharmaceutical Sciences, Berhampur-760010, Odisha, IndiaSchool of Pharmacy and Life Science, Centurion University of Technology and Management Bhubaneswar-751009, Odisha, IndiaObjective(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.https://nmj.mums.ac.ir/article_24729_285ef57c987090066db90e2add2fc123.pdfbioavailability potentialpolymeric nanoparticlesquality by designregorafenib monohydratezeta potential  
spellingShingle Dhananjay Panigrahi
Suryakanta Swain
Pratap Sahu
Debashish Ghose
Bikash Ranjan Jena
Quality by design enabled formulation development of regorafenib monohydrate loaded PEGylated PLGA polymeric nanoparticles: Enhanced oral bioavailability and biopharmaceutical attributes
Nanomedicine Journal
bioavailability potential
polymeric nanoparticles
quality by design
regorafenib monohydrate
zeta potential  
title Quality by design enabled formulation development of regorafenib monohydrate loaded PEGylated PLGA polymeric nanoparticles: Enhanced oral bioavailability and biopharmaceutical attributes
title_full Quality by design enabled formulation development of regorafenib monohydrate loaded PEGylated PLGA polymeric nanoparticles: Enhanced oral bioavailability and biopharmaceutical attributes
title_fullStr Quality by design enabled formulation development of regorafenib monohydrate loaded PEGylated PLGA polymeric nanoparticles: Enhanced oral bioavailability and biopharmaceutical attributes
title_full_unstemmed Quality by design enabled formulation development of regorafenib monohydrate loaded PEGylated PLGA polymeric nanoparticles: Enhanced oral bioavailability and biopharmaceutical attributes
title_short Quality by design enabled formulation development of regorafenib monohydrate loaded PEGylated PLGA polymeric nanoparticles: Enhanced oral bioavailability and biopharmaceutical attributes
title_sort quality by design enabled formulation development of regorafenib monohydrate loaded pegylated plga polymeric nanoparticles enhanced oral bioavailability and biopharmaceutical attributes
topic bioavailability potential
polymeric nanoparticles
quality by design
regorafenib monohydrate
zeta potential  
url https://nmj.mums.ac.ir/article_24729_285ef57c987090066db90e2add2fc123.pdf
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