Sustained Release Formulation of Hydroxypropyl-β-cyclodextrin Eye Drops Using Xanthan Gum

Bietti’s crystalline dystrophy (BCD) is an autosomal recessive chorioretinal degeneration caused by mutations in the CYP4V2 gene. It is characterized by cholesterol accumulation and crystal-like deposits in the retinas. Hydroxypropyl-β-cyclodextrin (HP-β-CyD) exerts therapeutic effects against BCD b...

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Veröffentlicht in:Chemical & pharmaceutical bulletin 2024/04/15, Vol.72(4), pp.381-384
Hauptverfasser: Higashi, Taishi, Goto, Taito, Onodera, Risako, Hirotsu, Tatsunori, Ikeda, Hanako Ohashi, Motoyama, Keiichi
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container_issue 4
container_start_page 381
container_title Chemical & pharmaceutical bulletin
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creator Higashi, Taishi
Goto, Taito
Onodera, Risako
Hirotsu, Tatsunori
Ikeda, Hanako Ohashi
Motoyama, Keiichi
description Bietti’s crystalline dystrophy (BCD) is an autosomal recessive chorioretinal degeneration caused by mutations in the CYP4V2 gene. It is characterized by cholesterol accumulation and crystal-like deposits in the retinas. Hydroxypropyl-β-cyclodextrin (HP-β-CyD) exerts therapeutic effects against BCD by reducing lysosomal dysfunction and inhibiting cytotoxicity in induced pluripotent stem cell (iPSC)-RPE cells established from patient-derived iPS cells. However, the ocular retention of HP-β-CyD is low and needs to be improved. Therefore, this study used a viscous agent to develop a sustained-release ophthalmic formulation containing HP-β-CyD. Our results suggest that HP-β-CyD-containing xanthan gum has a considerably higher sustained release capacity than other viscous agents, such as methylcellulose and sodium alginate. In addition, the HP-β-CyD-containing xanthan gum exhibited pseudoplastic behavior. It was less cytotoxic to human retinal pigment epithelial cells compared with HP-β-CyD alone. Furthermore, the slow release of HP-β-CyD from xanthan gum caused a sustained decrease in free intracellular cholesterol. These results suggest that xanthan gum is a useful substrate for the sustained release formulation of HP-β-CyD, and that HP-β-CyD-containing xanthan gum has potential as an eye drop for BCD treatment.
doi_str_mv 10.1248/cpb.c24-00059
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subjects 2-Hydroxypropyl-beta-cyclodextrin - pharmacology
Alginic acid
Bietti’s crystalline dystrophy
Cholesterol
Controlled release
Corneal Dystrophies, Hereditary
Cyclodextrins
Cytotoxicity
Degeneration
Delayed-Action Preparations - pharmacology
Dystrophy
Epithelium
Eye (anatomy)
eye drop
Humans
hydroxypropyl-β-cyclodextrin
Methylcellulose
Pluripotency
Polysaccharides, Bacterial
Pseudoplasticity
Reagents
Retinal Diseases
Retinal pigment epithelium
Sodium alginate
Stem cells
Substrates
Sustained release
Xanthan
Xanthan gum
β-Cyclodextrin
title Sustained Release Formulation of Hydroxypropyl-β-cyclodextrin Eye Drops Using Xanthan Gum
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