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Curr Pharm Des. 2019;25(46):4883-4892. doi: 10.2174/1381612825666191106150018.

Enhancing the Therapeutic Efficacy of Bortezomib in Cancer Therapy Using Polymeric Nanostructures.

Author information

1
Nanotechnology Research Center, Buali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
2
Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
3
Research Center of Oils and Fats, Kermanshah University of Medical Sciences, Kermanshah, Iran.
4
Department of Biochemistry and Biophysics, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
5
Department of Pharmaceutics, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
6
Immunogenetic and Cell Culture Department, Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
7
Department of Pharmaceutics, Faculty of Pharmacy, University of Ahl Al Bayt, Karbala, Iraq.
8
Department of Pharmaceutics, Faculty of Pharmacy, Al- Zahraa University, Karbala, Iraq.
9
Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri- Kansas City, Kansas City, Missouri, United States.
10
Halal Research Center of IRI, FDA, Tehran, Iran.
11
Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
12
Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

Bortezomib (VELCADE®) is a boronate peptide and first-in-class proteasome inhibitor serving an important role in degenerating several intracellular proteins. It is a reversible inhibitor of the 26S proteasome, with antitumor activity and antiproliferative properties. This agent principally exerts its antineoplastic effects by inhibiting key players in the nuclear factor κB (NFκB) pathway involved in cell proliferation, apoptosis, and angiogenesis. This medication is used in the management of multiple myeloma. However, more recently, it has been used as a therapeutic option for mantle cell lymphoma. While promising, bortezomib has limited clinical applications due to its adverse effects (e.g., hematotoxicity and peripheral neuropathy) and low effectiveness in solid tumors resulting from its poor penetration into such masses and suboptimal pharmacokinetic parameters. Other limitations to bortezomib include its low chemical stability and bioavailability, which can be overcome by using nanoparticles for its delivery. Nanoparticle delivery systems can facilitate the targeted delivery of chemotherapeutic agents in high doses to the target site, while sparing healthy tissues. Therefore, this drug delivery system has provided a solution to circumvent the limitations faced with the delivery of traditional cancer chemotherapeutic agents. Our aim in this review was to describe polymer-based nanocarriers that can be used for the delivery of bortezomib in cancer chemotherapy.

KEYWORDS:

Bortezomib; drug delivery system; hematotoxicity; peripheral neuropathy; polymer-based nanocarriers; proteasome inhibitor.

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