Bexarotene nanocrystal—Oral and parenteral formulation development, characterization and pharmacokinetic evaluation
Abstract
Bexarotene (Targretin®) is a synthetic retinoid that selectively activates the retinoid X receptor subfamily of retinoid receptors and exhibits potent anti-tumor activity. However, the poor solubility and bioavailability limit its application. The main aim of this study is to investigate the potential of oral and parenteral nanocrystals in enhancing the bioavailability of bexarotene. In this work, the orthogonal design was used to screen the optimum stabilizers and precipitation-combined microfluidization method was employed to obtain the optimal nanocrystals. According to DSC, X-ray diffraction analysis and Raman examination, the nanocrystals were still in crystalline state after the preparation procedure. By reducing the particle size, the in vitro dissolution rate of bexarotene was increased significantly. The in vivo test was carried out in rats and pharmacokinetic parameters of the bexarotene solution and bexarotene nanocrystals were compared after gavage and intravenous administration. The higher AUC and lower Cmax indicated that oral bexarotene nanocrystals significantly increased the bioavailability of bexarotene and decreased its side effects. Compared to the oral nanocrystals, the intravenous nanocrystals cut losses and increased bioavailability because of the absence of first pass effect and enterohepatic circulation.
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A review by Tesseur and DeStrooper documented that a critical difference between these studies was the drug formulation, which dramatically affects the pharmacodynamics of bexarotene.
“A review of this literature by Tesseur and DeStrooper documented that a critical difference between these studies was the drug formulation46 which dramatically affect the pharmacodynamics of bexarotene49.”
From Neuronally-directed effects of RXR activation in a mouse model of Alzheimer’s disease (2017) · cites this paper as [49]
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- Authors
- Chen, L., Wang, Y., Zhang, J., Hao, L., Guo, H., Lou, H., & Zhang, D.
- Affiliations
- Liaoning University (CN)
- Shandong University (CN)
- Corresponding author
- Zhang, Dianrui
- Venue
- European Journal of Pharmaceutics and Biopharmaceutics
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 87
- Issue
- 1
- Pages
- 160-169
- ISSN
- 0939-6411 (ISSN-L)
- OpenAlex
- W2094401613
- Cited by
- 78
- References
- 53
- Citations by year
- 2026: 6 · 2025: 1 · 2024: 4 · 2023: 6 · 2022: 10 · 2021: 6 · 2020: 9 · 2019: 5 · 2018: 6 · 2017: 9 · 2016: 7 · 2015: 3 · 2014: 5
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmaceutics and Biopharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Key Research and Development Program of China
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- bexarotene, nanocrystals, oral dosage forms, parenteral formulations, bioavailability enhancement, poorly water-soluble drugs, retinoid X receptor, dissolution rate, pharmacokinetics, first-pass metabolism, enterohepatic circulation, particle size reduction
- MeSH terms
- Bexarotene, Administration, Oral, Animals, Antineoplastic Agents, Drug Carriers, Freeze Drying, Particle Size, Solubility, Spectrum Analysis, Raman, Surface Properties, Tetrahydronaphthalenes, Tissue Distribution, Rats, Wistar, Microscopy, Electron, Transmission, Retinoid X Receptors, Nanoparticles, Drug Liberation
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