Publication:
Anti-angiogenesis by dual action of R5K peptide conjugated itraconazole nanoparticles

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Issued Date

2020

Resource Type

Article

File Type

application/pdf

ISSN

15309932

DOI

10.1208/s12249-019-1568-8

Other identifier(s)

2-s2.0-85078246456

Rights Holder(s)

Scopus

Bibliographic Citation

AAPS PharmSciTech. Vol 21, No.3 (2020), p.-

Suggested Citation

Chittasupho C., Kengtrong K., Chalermnithiwong S., Sarisuta N. Anti-angiogenesis by dual action of R5K peptide conjugated itraconazole nanoparticles. AAPS PharmSciTech. Vol 21, No.3 (2020), p.-. doi:10.1208/s12249-019-1568-8 Retrieved from: https://hdl.handle.net/20.500.14740/4612

Title

Anti-angiogenesis by dual action of R5K peptide conjugated itraconazole nanoparticles

Author(s)

Chittasupho C.
 Kengtrong K.
 Chalermnithiwong S.
 Sarisuta N.

Abstract

Neovascular age-related macular degeneration (AMD) is a leading cause of central vision loss and irreversible blindness. Vascular endothelial growth factor (VEGF) plays an important role in neovascularization under the retina and macula by promoting endothelial cell proliferation, migration, and angiogenesis. Although anti-VEGF drugs have shown their efficacy in visual improvement, long-term use of these drugs leads to ocular and systemic complications due to the non-selectivity of the drug. In this study, the dual-mode anti-angiogenic drug delivery system, which potentially inhibited VEGF in two different ways, was developed. The itraconazole encapsulated nanoparticles, conjugated with R5K peptide, were fabricated to allow multivalent binding interactions with VEGF. The R5K peptide blocked VEGF binding to its receptor, while itraconazole altered the signaling pathway of VEGF stimulation. The dual action of this novel drug delivery system aimed to enhance the anti-angiogenic effects of individual drugs. R5K-ITZ-NPs demonstrated potent, cell-type specific, and dose-dependent inhibition of vascular endothelial cell proliferation, migration, and tube formation in response to VEGF stimulation. The physical stability study showed that R5K-ITZ-NPs were stable when stored at 4 °C. However, the drug remaining in R5K-ITZ-NPs when stored at 4 °C for 28 days were only 17.2%. The chemical stability test revealed that the degradation of R5K-ITZ-NPs followed second-order kinetics. The release profile showed the burst release of ITZ followed by sustained release of the drug This novel drug delivery system may be an option for neovascular AMD patients who are resistant to ITZ and may represent a novel therapy for AMD. © 2020, American Association of Pharmaceutical Scientists.

Subject(s)

Arginylarginyllysylarginylarginylarginine
 Hexapeptide
 Hyaluronic acid
 Itraconazole
 Nanoparticle
 Polyglactin
 Unclassified drug
 Vasculotropin
 Angiogenesis inhibitor
 Cytochrome P450 3A inhibitor
 Itraconazole
 Peptide fragment
 Vasculotropin A
 Antiangiogenic activity
 Article
 Cell migration
 Cell proliferation
 Cell viability
 Dispersity
 Drug bioavailability
 Drug delivery system
 Drug release
 Human
 Human cell
 IC50
 Particle size
 Priority journal
 Signal transduction
 Temperature
 Vascular endothelial cell
 Zeta potential
 Cell survival
 Dose response
 Drug effect
 Metabolism
 Physiology
 Umbilical vein endothelial cell
 Visual acuity
 Wet macular degeneration
 Angiogenesis Inhibitors
 Cell Survival
 Cytochrome P-450 CYP3A Inhibitors
 Dose-Response Relationship, Drug
 Human Umbilical Vein Endothelial Cells
 Humans
 Itraconazole
 Nanoparticles
 Peptide Fragments
 Vascular Endothelial Growth Factor A
 Visual Acuity
 Wet Macular Degeneration

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URI

https://hdl.handle.net/20.500.14740/4612

Collections

Scopus: Year 1983-2021

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