Spray-Dried Polyelectrolyte Microparticles in Oral Antigen Delivery: Stability, Biocompatibility, and Cellular Uptake
During the past decade, extensive research has undeniably improved the formulation and delivery of oral vaccines. Nevertheless, several factors, such as the harsh gastrointestinal environment together with tolerance induction to exogenous antigens, have thus far impeded the optimal effectiveness and...
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| Veröffentlicht in: | Biomacromolecules 2014-06, Vol.15 (6), p.2301-2309 |
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| creator | De Smet, Rebecca Verschuere, Stephanie Allais, Liesbeth Leclercq, Georges Dierendonck, Marijke De Geest, Bruno G Van Driessche, Isabel Demoor, Tine Cuvelier, Claude A |
| description | During the past decade, extensive research has undeniably improved the formulation and delivery of oral vaccines. Nevertheless, several factors, such as the harsh gastrointestinal environment together with tolerance induction to exogenous antigens, have thus far impeded the optimal effectiveness and clinical application of oral delivery systems. The current study encompasses an initial evaluation of the stability, biocompatibility, and cellular uptake of two promising candidate systems for oral antigen delivery, that is, calcium carbonate- (CP) and mannitol-templated (MP) porous microspheres. Both spray-dried formulations were efficiently internalized by human intestinal epithelial cells (Caco-2 and HT-29) and degraded into phagolysosomal intracellular compartments. In addition, cellular particle uptake and processing significantly up-regulated the expression of (HLA) class-II and costimulatory molecules on intestinal epithelial cells. Even though the high surface-area-to-volume ratio of the microspheres was expected to favor protease access, antigen release was remarkably limited in simulated intestinal fluid and was even absent under gastric conditions. Finally, neither CP nor MP exerted cytotoxicity upon prolonged in vitro incubation with high antigen concentration. Altogether, these data support the potential of CP and MP for oral antigen delivery and motivate the further development of these promising carrier systems in in vivo studies. |
| doi_str_mv | 10.1021/bm5005367 |
| format | Article |
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Nevertheless, several factors, such as the harsh gastrointestinal environment together with tolerance induction to exogenous antigens, have thus far impeded the optimal effectiveness and clinical application of oral delivery systems. The current study encompasses an initial evaluation of the stability, biocompatibility, and cellular uptake of two promising candidate systems for oral antigen delivery, that is, calcium carbonate- (CP) and mannitol-templated (MP) porous microspheres. Both spray-dried formulations were efficiently internalized by human intestinal epithelial cells (Caco-2 and HT-29) and degraded into phagolysosomal intracellular compartments. In addition, cellular particle uptake and processing significantly up-regulated the expression of (HLA) class-II and costimulatory molecules on intestinal epithelial cells. Even though the high surface-area-to-volume ratio of the microspheres was expected to favor protease access, antigen release was remarkably limited in simulated intestinal fluid and was even absent under gastric conditions. Finally, neither CP nor MP exerted cytotoxicity upon prolonged in vitro incubation with high antigen concentration. Altogether, these data support the potential of CP and MP for oral antigen delivery and motivate the further development of these promising carrier systems in in vivo studies.</description><identifier>ISSN: 1525-7797</identifier><identifier>EISSN: 1526-4602</identifier><identifier>DOI: 10.1021/bm5005367</identifier><identifier>PMID: 24805802</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Administration, Oral ; Antigens - administration & dosage ; Antigens - metabolism ; Applied sciences ; Biocompatible Materials - administration & dosage ; Biocompatible Materials - metabolism ; Biological and medical sciences ; Caco-2 Cells ; Cell Survival - drug effects ; Cell Survival - physiology ; Drug Delivery Systems - methods ; Drug Stability ; Exact sciences and technology ; Forms of application and semi-finished materials ; General pharmacology ; HT29 Cells ; Humans ; Medical sciences ; Microspheres ; Miscellaneous ; Ovalbumin - administration & dosage ; Ovalbumin - metabolism ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Polymer industry, paints, wood ; Serum Albumin, Bovine - administration & dosage ; Serum Albumin, Bovine - metabolism ; Technology of polymers</subject><ispartof>Biomacromolecules, 2014-06, Vol.15 (6), p.2301-2309</ispartof><rights>Copyright © 2014 American Chemical Society</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a378t-6e7c70bccaa2fbf292b37ce0380efb55371b71ad1c17d6df33bc4317a57455ec3</citedby><cites>FETCH-LOGICAL-a378t-6e7c70bccaa2fbf292b37ce0380efb55371b71ad1c17d6df33bc4317a57455ec3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/bm5005367$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/bm5005367$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>315,781,785,2766,27078,27926,27927,56740,56790</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28605237$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24805802$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>De Smet, Rebecca</creatorcontrib><creatorcontrib>Verschuere, Stephanie</creatorcontrib><creatorcontrib>Allais, Liesbeth</creatorcontrib><creatorcontrib>Leclercq, Georges</creatorcontrib><creatorcontrib>Dierendonck, Marijke</creatorcontrib><creatorcontrib>De Geest, Bruno G</creatorcontrib><creatorcontrib>Van Driessche, Isabel</creatorcontrib><creatorcontrib>Demoor, Tine</creatorcontrib><creatorcontrib>Cuvelier, Claude A</creatorcontrib><title>Spray-Dried Polyelectrolyte Microparticles in Oral Antigen Delivery: Stability, Biocompatibility, and Cellular Uptake</title><title>Biomacromolecules</title><addtitle>Biomacromolecules</addtitle><description>During the past decade, extensive research has undeniably improved the formulation and delivery of oral vaccines. Nevertheless, several factors, such as the harsh gastrointestinal environment together with tolerance induction to exogenous antigens, have thus far impeded the optimal effectiveness and clinical application of oral delivery systems. The current study encompasses an initial evaluation of the stability, biocompatibility, and cellular uptake of two promising candidate systems for oral antigen delivery, that is, calcium carbonate- (CP) and mannitol-templated (MP) porous microspheres. Both spray-dried formulations were efficiently internalized by human intestinal epithelial cells (Caco-2 and HT-29) and degraded into phagolysosomal intracellular compartments. In addition, cellular particle uptake and processing significantly up-regulated the expression of (HLA) class-II and costimulatory molecules on intestinal epithelial cells. Even though the high surface-area-to-volume ratio of the microspheres was expected to favor protease access, antigen release was remarkably limited in simulated intestinal fluid and was even absent under gastric conditions. Finally, neither CP nor MP exerted cytotoxicity upon prolonged in vitro incubation with high antigen concentration. Altogether, these data support the potential of CP and MP for oral antigen delivery and motivate the further development of these promising carrier systems in in vivo studies.</description><subject>Administration, Oral</subject><subject>Antigens - administration & dosage</subject><subject>Antigens - metabolism</subject><subject>Applied sciences</subject><subject>Biocompatible Materials - administration & dosage</subject><subject>Biocompatible Materials - metabolism</subject><subject>Biological and medical sciences</subject><subject>Caco-2 Cells</subject><subject>Cell Survival - drug effects</subject><subject>Cell Survival - physiology</subject><subject>Drug Delivery Systems - methods</subject><subject>Drug Stability</subject><subject>Exact sciences and technology</subject><subject>Forms of application and semi-finished materials</subject><subject>General pharmacology</subject><subject>HT29 Cells</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Microspheres</subject><subject>Miscellaneous</subject><subject>Ovalbumin - administration & dosage</subject><subject>Ovalbumin - metabolism</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Polymer industry, paints, wood</subject><subject>Serum Albumin, Bovine - administration & dosage</subject><subject>Serum Albumin, Bovine - metabolism</subject><subject>Technology of polymers</subject><issn>1525-7797</issn><issn>1526-4602</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0ctO3TAQBmALteJWFrwA8qYSlRrqa5zTHRx6QQJRCVhHY2dSmTqX2k6lvD2hHGDTRVceWZ9mRvMTcsjZCWeCf7KdZkzL0myRXa5FWaiSiTd_a10YszI7ZC-le8bYSiq9TXaEqpiumNgl080YYS7Oo8eG_hjCjAFdjkuRkV55F4cRYvYuYKK-p9cRAj3ts_-JPT3H4P9gnD_TmwzWB5_nj_TMD27oRsj--Qf6hq4xhClApHdjhl_4jrxtISQ82Lz75O7rl9v19-Ly-tvF-vSyAGmqXJRonGHWOQDR2lashJXGIZMVw9ZqLQ23hkPDHTdN2bRSWqckN6CN0hqd3CfHT33HOPyeMOW688ktu0CPw5RqrpVinKtS_QeVShmhtVnohye6XCeliG09Rt9BnGvO6sdA6pdAFnu0aTvZDpsX-ZzAAt5vACQHoY3QO59eXVUyLaR5deBSfT9MsV8O94-BD4Y0nzM</recordid><startdate>20140609</startdate><enddate>20140609</enddate><creator>De Smet, Rebecca</creator><creator>Verschuere, Stephanie</creator><creator>Allais, Liesbeth</creator><creator>Leclercq, Georges</creator><creator>Dierendonck, Marijke</creator><creator>De Geest, Bruno G</creator><creator>Van Driessche, Isabel</creator><creator>Demoor, Tine</creator><creator>Cuvelier, Claude A</creator><general>American Chemical Society</general><scope>IQODW</scope><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>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20140609</creationdate><title>Spray-Dried Polyelectrolyte Microparticles in Oral Antigen Delivery: Stability, Biocompatibility, and Cellular Uptake</title><author>De Smet, Rebecca ; Verschuere, Stephanie ; Allais, Liesbeth ; Leclercq, Georges ; Dierendonck, Marijke ; De Geest, Bruno G ; Van Driessche, Isabel ; Demoor, Tine ; Cuvelier, Claude A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a378t-6e7c70bccaa2fbf292b37ce0380efb55371b71ad1c17d6df33bc4317a57455ec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Administration, Oral</topic><topic>Antigens - administration & dosage</topic><topic>Antigens - metabolism</topic><topic>Applied sciences</topic><topic>Biocompatible Materials - administration & dosage</topic><topic>Biocompatible Materials - metabolism</topic><topic>Biological and medical sciences</topic><topic>Caco-2 Cells</topic><topic>Cell Survival - drug effects</topic><topic>Cell Survival - physiology</topic><topic>Drug Delivery Systems - methods</topic><topic>Drug Stability</topic><topic>Exact sciences and technology</topic><topic>Forms of application and semi-finished materials</topic><topic>General pharmacology</topic><topic>HT29 Cells</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Microspheres</topic><topic>Miscellaneous</topic><topic>Ovalbumin - administration & dosage</topic><topic>Ovalbumin - metabolism</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. 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| subjects | Administration, Oral Antigens - administration & dosage Antigens - metabolism Applied sciences Biocompatible Materials - administration & dosage Biocompatible Materials - metabolism Biological and medical sciences Caco-2 Cells Cell Survival - drug effects Cell Survival - physiology Drug Delivery Systems - methods Drug Stability Exact sciences and technology Forms of application and semi-finished materials General pharmacology HT29 Cells Humans Medical sciences Microspheres Miscellaneous Ovalbumin - administration & dosage Ovalbumin - metabolism Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Polymer industry, paints, wood Serum Albumin, Bovine - administration & dosage Serum Albumin, Bovine - metabolism Technology of polymers |
| title | Spray-Dried Polyelectrolyte Microparticles in Oral Antigen Delivery: Stability, Biocompatibility, and Cellular Uptake |
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