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 |
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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. |
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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.</description><identifier>ISSN: 0009-2363</identifier><identifier>EISSN: 1347-5223</identifier><identifier>DOI: 10.1248/cpb.c24-00059</identifier><identifier>PMID: 38616116</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>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</subject><ispartof>Chemical and Pharmaceutical Bulletin, 2024/04/15, Vol.72(4), pp.381-384</ispartof><rights>2024 Author(s) This is an open access article distributed under the terms of Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/). Published by The Pharmaceutical Society of Japan</rights><rights>2024. This work is published under https://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c486t-e730177718821be8db7367dfa1bf36ef5e3597c18463585df0ae90425ef4bd463</citedby><cites>FETCH-LOGICAL-c486t-e730177718821be8db7367dfa1bf36ef5e3597c18463585df0ae90425ef4bd463</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,1877,4010,27904,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38616116$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Higashi, Taishi</creatorcontrib><creatorcontrib>Goto, Taito</creatorcontrib><creatorcontrib>Onodera, Risako</creatorcontrib><creatorcontrib>Hirotsu, Tatsunori</creatorcontrib><creatorcontrib>Ikeda, Hanako Ohashi</creatorcontrib><creatorcontrib>Motoyama, Keiichi</creatorcontrib><title>Sustained Release Formulation of Hydroxypropyl-β-cyclodextrin Eye Drops Using Xanthan Gum</title><title>Chemical & pharmaceutical bulletin</title><addtitle>Chem. Pharm. Bull.</addtitle><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.</description><subject>2-Hydroxypropyl-beta-cyclodextrin - pharmacology</subject><subject>Alginic acid</subject><subject>Bietti’s crystalline dystrophy</subject><subject>Cholesterol</subject><subject>Controlled release</subject><subject>Corneal Dystrophies, Hereditary</subject><subject>Cyclodextrins</subject><subject>Cytotoxicity</subject><subject>Degeneration</subject><subject>Delayed-Action Preparations - pharmacology</subject><subject>Dystrophy</subject><subject>Epithelium</subject><subject>Eye (anatomy)</subject><subject>eye drop</subject><subject>Humans</subject><subject>hydroxypropyl-β-cyclodextrin</subject><subject>Methylcellulose</subject><subject>Pluripotency</subject><subject>Polysaccharides, Bacterial</subject><subject>Pseudoplasticity</subject><subject>Reagents</subject><subject>Retinal Diseases</subject><subject>Retinal pigment epithelium</subject><subject>Sodium alginate</subject><subject>Stem cells</subject><subject>Substrates</subject><subject>Sustained release</subject><subject>Xanthan</subject><subject>Xanthan gum</subject><subject>β-Cyclodextrin</subject><issn>0009-2363</issn><issn>1347-5223</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkE1r3DAQhkVpabZpj70WQS-9KNWnJR_LNl8QKCQNlF6ELI8TL7a0lWyI_1Z-SH5TlWyyhc5hBmYeXoYHoY-MHjEuzVe_bY48l4RSqupXaMWE1ERxLl6jVdnVhItKHKB3OW8o5Ypq8RYdCFOxirFqhX5fzXlyfYAWX8IALgM-iWmcBzf1MeDY4bOlTfFu2aa4XQbycE_84ofYwt2U-oCPF8Dfyynj69yHG_zLhenWBXw6j-_Rm84NGT48z0N0fXL8c31GLn6cnq-_XRAvTTUR0IIyrTUzhrMGTNtoUem2c6zpRAWdAqFq7ZmRlVBGtR11UFPJFXSyacvyEH3Z5ZYX_8yQJzv22cMwuABxzlZQUXNRyhT083_oJs4plO8KpWRVG2pkociO8inmnKCz29SPLi2WUfso3Rbptki3T9IL_-k5dW5GaPf0i-UCrHfApri-gT3g0tT7AZ7iNLfyse1j_11vXbIQxF-se5WO</recordid><startdate>2024</startdate><enddate>2024</enddate><creator>Higashi, Taishi</creator><creator>Goto, Taito</creator><creator>Onodera, Risako</creator><creator>Hirotsu, Tatsunori</creator><creator>Ikeda, Hanako Ohashi</creator><creator>Motoyama, Keiichi</creator><general>The Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>2024</creationdate><title>Sustained Release Formulation of Hydroxypropyl-β-cyclodextrin Eye Drops Using Xanthan Gum</title><author>Higashi, Taishi ; Goto, Taito ; Onodera, Risako ; Hirotsu, Tatsunori ; Ikeda, Hanako Ohashi ; Motoyama, Keiichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c486t-e730177718821be8db7367dfa1bf36ef5e3597c18463585df0ae90425ef4bd463</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>2-Hydroxypropyl-beta-cyclodextrin - pharmacology</topic><topic>Alginic acid</topic><topic>Bietti’s crystalline dystrophy</topic><topic>Cholesterol</topic><topic>Controlled release</topic><topic>Corneal Dystrophies, Hereditary</topic><topic>Cyclodextrins</topic><topic>Cytotoxicity</topic><topic>Degeneration</topic><topic>Delayed-Action Preparations - pharmacology</topic><topic>Dystrophy</topic><topic>Epithelium</topic><topic>Eye (anatomy)</topic><topic>eye drop</topic><topic>Humans</topic><topic>hydroxypropyl-β-cyclodextrin</topic><topic>Methylcellulose</topic><topic>Pluripotency</topic><topic>Polysaccharides, Bacterial</topic><topic>Pseudoplasticity</topic><topic>Reagents</topic><topic>Retinal Diseases</topic><topic>Retinal pigment epithelium</topic><topic>Sodium alginate</topic><topic>Stem cells</topic><topic>Substrates</topic><topic>Sustained release</topic><topic>Xanthan</topic><topic>Xanthan gum</topic><topic>β-Cyclodextrin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Higashi, Taishi</creatorcontrib><creatorcontrib>Goto, Taito</creatorcontrib><creatorcontrib>Onodera, Risako</creatorcontrib><creatorcontrib>Hirotsu, Tatsunori</creatorcontrib><creatorcontrib>Ikeda, Hanako Ohashi</creatorcontrib><creatorcontrib>Motoyama, Keiichi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Chemical & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Higashi, Taishi</au><au>Goto, Taito</au><au>Onodera, Risako</au><au>Hirotsu, Tatsunori</au><au>Ikeda, Hanako Ohashi</au><au>Motoyama, Keiichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sustained Release Formulation of Hydroxypropyl-β-cyclodextrin Eye Drops Using Xanthan Gum</atitle><jtitle>Chemical & pharmaceutical bulletin</jtitle><addtitle>Chem. Pharm. Bull.</addtitle><date>2024</date><risdate>2024</risdate><volume>72</volume><issue>4</issue><spage>381</spage><epage>384</epage><pages>381-384</pages><artnum>c24-00059</artnum><issn>0009-2363</issn><eissn>1347-5223</eissn><abstract>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.</abstract><cop>Japan</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>38616116</pmid><doi>10.1248/cpb.c24-00059</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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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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