In situ chemically crosslinked injectable hydrogels for the subcutaneous delivery of trastuzumab to treat breast cancer
[Display omitted] Recently, novel approaches for the delivery of therapeutic antibodies have attracted much attention, especially sustained release formulations. However, sustained release formulations capable of carrying a high antibody load remain a challenge for practical use. In this study, a no...
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| Veröffentlicht in: | Acta biomaterialia 2019-03, Vol.86, p.280-290 |
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| creator | Lo, Yu-Wen Sheu, Ming-Thau Chiang, Wen-Hsuan Chiu, Ya-Ling Tu, Chia-Mu Wang, Wen-Yu Wu, Ming-Hsi Wang, Yu-Cheng Lu, Maggie Ho, Hsiu-O |
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Recently, novel approaches for the delivery of therapeutic antibodies have attracted much attention, especially sustained release formulations. However, sustained release formulations capable of carrying a high antibody load remain a challenge for practical use. In this study, a novel injectable hydrogel composed of maleimide-modified γ-polyglutamic acid (γ-PGA-MA) and thiol end-functionalized 4-arm poly(ethylene glycol) (4-arm PEG-SH) was developed for the subcutaneous delivery of trastuzumab. γ-PGA-MA and 4-arm PEG-SH formed a hydrogel through thiol-maleimide reactions, which had shear-thinning properties and reversible rheological behaviors. Moreover, a high content of trastuzumab (>100 mg/mL) could be loaded into this hydrogel, and trastuzumab demonstrated a sustained release over several weeks through electrostatic attraction. In addition, trastuzumab released from the hydrogel had adequate stability in terms of its structural integrity, binding bioactivity, and antiproliferative effect on BT-474 cells. Pharmacokinetic studies demonstrated that trastuzumab-loaded hydrogel (Her-hydrogel-10, composed of 1.5% γ-PGA-MA, 1.5% 4-arm PEG-SH, and 10 mg/mL trastuzumab) and trastuzumab/Zn-loaded hydrogel (Her/Zn-hydrogel-10, composed of 1.5% γ-PGA-MA, 1.5% 4-arm PEG-SH, 5 mM ZnCl2, and 10 mg/mL trastuzumab) could lower the maximum plasma concentration (Cmax) than the trastuzumab solution. Furthermore, Her/Zn-hydrogel-10 was better able to release trastuzumab in a controlled manner, which was ascribed to electrostatic attraction and formation of trastuzumab/Zn nanocomplexes. In a BT-474 xenograft tumor model, Her-hydrogel-10 had a similar tumor growth-inhibitory effect as that of the trastuzumab solution. By contrast, Her/Zn-hydrogel-10 exhibited a superior tumor growth-inhibitory capability due to the functionality of Zn. This study demonstrated that this hydrogel has potential as a carrier for the local and systemic delivery of proteins and antibodies.
Recently, novel sustained-release formulations of therapeutic antibodies have attracted much attention. However, these formulations should be able to carry a high antibody load owing to the required high dose, and these formulations remain a challenge for practical use. In this study, a novel injectable chemically cross-linked hydrogel was developed for the subcutaneous delivery of trastuzumab. This novel hydrogel possessed ideal characteristics of loading high content of trastuzumab (>100 mg/m |
| doi_str_mv | 10.1016/j.actbio.2019.01.003 |
| format | Article |
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Recently, novel approaches for the delivery of therapeutic antibodies have attracted much attention, especially sustained release formulations. However, sustained release formulations capable of carrying a high antibody load remain a challenge for practical use. In this study, a novel injectable hydrogel composed of maleimide-modified γ-polyglutamic acid (γ-PGA-MA) and thiol end-functionalized 4-arm poly(ethylene glycol) (4-arm PEG-SH) was developed for the subcutaneous delivery of trastuzumab. γ-PGA-MA and 4-arm PEG-SH formed a hydrogel through thiol-maleimide reactions, which had shear-thinning properties and reversible rheological behaviors. Moreover, a high content of trastuzumab (>100 mg/mL) could be loaded into this hydrogel, and trastuzumab demonstrated a sustained release over several weeks through electrostatic attraction. In addition, trastuzumab released from the hydrogel had adequate stability in terms of its structural integrity, binding bioactivity, and antiproliferative effect on BT-474 cells. Pharmacokinetic studies demonstrated that trastuzumab-loaded hydrogel (Her-hydrogel-10, composed of 1.5% γ-PGA-MA, 1.5% 4-arm PEG-SH, and 10 mg/mL trastuzumab) and trastuzumab/Zn-loaded hydrogel (Her/Zn-hydrogel-10, composed of 1.5% γ-PGA-MA, 1.5% 4-arm PEG-SH, 5 mM ZnCl2, and 10 mg/mL trastuzumab) could lower the maximum plasma concentration (Cmax) than the trastuzumab solution. Furthermore, Her/Zn-hydrogel-10 was better able to release trastuzumab in a controlled manner, which was ascribed to electrostatic attraction and formation of trastuzumab/Zn nanocomplexes. In a BT-474 xenograft tumor model, Her-hydrogel-10 had a similar tumor growth-inhibitory effect as that of the trastuzumab solution. By contrast, Her/Zn-hydrogel-10 exhibited a superior tumor growth-inhibitory capability due to the functionality of Zn. This study demonstrated that this hydrogel has potential as a carrier for the local and systemic delivery of proteins and antibodies.
Recently, novel sustained-release formulations of therapeutic antibodies have attracted much attention. However, these formulations should be able to carry a high antibody load owing to the required high dose, and these formulations remain a challenge for practical use. In this study, a novel injectable chemically cross-linked hydrogel was developed for the subcutaneous delivery of trastuzumab. This novel hydrogel possessed ideal characteristics of loading high content of trastuzumab (>100 mg/mL), sustained release of trastuzumab over several weeks, and maintaining adequate stability of trastuzumab. In vivo studies demonstrated that a trastuzumab-loaded hydrogel possessed the ability of controlled release of trastuzumab and maintained antitumor efficacy same as that of trastuzumab. These results implied that a γ-PGA-MA and 4-arm PEG-SH-based hydrogel has great potential in serving as a carrier for the local or systemic delivery of therapeutic proteins or antibodies.</description><identifier>ISSN: 1742-7061</identifier><identifier>EISSN: 1878-7568</identifier><identifier>DOI: 10.1016/j.actbio.2019.01.003</identifier><identifier>PMID: 30616077</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Antibodies ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Attraction ; Biological activity ; Body Weight - drug effects ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - pathology ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Controlled release ; Cross-Linking Reagents - chemistry ; Crosslinking ; Drug Delivery Systems ; Drug Liberation ; Female ; Formulations ; Humans ; Hydrogels ; Hydrogels - chemistry ; Immunotherapy ; Injectable hydrogels ; Injections ; Maleimide-modified γ-polyglutamic acid ; Maleimides - chemical synthesis ; Maleimides - chemistry ; Mice, SCID ; Monoclonal antibodies ; Organic chemistry ; Pharmacology ; Polyethylene glycol ; Polyglutamic Acid - analogs & derivatives ; Polyglutamic Acid - chemical synthesis ; Polyglutamic Acid - chemistry ; Proteins ; Rats, Sprague-Dawley ; Rheological properties ; Rheology ; Structural integrity ; Sustained release ; Targeted cancer therapy ; Thiol end-functionalized 4-arm poly(ethylene glycol) ; Trastuzumab ; Trastuzumab - administration & dosage ; Trastuzumab - chemistry ; Trastuzumab - pharmacology ; Trastuzumab - therapeutic use ; Tumors ; Xenograft Model Antitumor Assays ; Xenografts ; Xenotransplantation ; Zinc ; Zinc chloride</subject><ispartof>Acta biomaterialia, 2019-03, Vol.86, p.280-290</ispartof><rights>2019 Acta Materialia Inc.</rights><rights>Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier BV Mar 1, 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-a84c88a9f90383a0c74729ead80acfc3fde35ce2c108256cf6d062c5f3ee47803</citedby><cites>FETCH-LOGICAL-c390t-a84c88a9f90383a0c74729ead80acfc3fde35ce2c108256cf6d062c5f3ee47803</cites><orcidid>0000-0003-1995-8369</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.actbio.2019.01.003$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30616077$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lo, Yu-Wen</creatorcontrib><creatorcontrib>Sheu, Ming-Thau</creatorcontrib><creatorcontrib>Chiang, Wen-Hsuan</creatorcontrib><creatorcontrib>Chiu, Ya-Ling</creatorcontrib><creatorcontrib>Tu, Chia-Mu</creatorcontrib><creatorcontrib>Wang, Wen-Yu</creatorcontrib><creatorcontrib>Wu, Ming-Hsi</creatorcontrib><creatorcontrib>Wang, Yu-Cheng</creatorcontrib><creatorcontrib>Lu, Maggie</creatorcontrib><creatorcontrib>Ho, Hsiu-O</creatorcontrib><title>In situ chemically crosslinked injectable hydrogels for the subcutaneous delivery of trastuzumab to treat breast cancer</title><title>Acta biomaterialia</title><addtitle>Acta Biomater</addtitle><description>[Display omitted]
Recently, novel approaches for the delivery of therapeutic antibodies have attracted much attention, especially sustained release formulations. However, sustained release formulations capable of carrying a high antibody load remain a challenge for practical use. In this study, a novel injectable hydrogel composed of maleimide-modified γ-polyglutamic acid (γ-PGA-MA) and thiol end-functionalized 4-arm poly(ethylene glycol) (4-arm PEG-SH) was developed for the subcutaneous delivery of trastuzumab. γ-PGA-MA and 4-arm PEG-SH formed a hydrogel through thiol-maleimide reactions, which had shear-thinning properties and reversible rheological behaviors. Moreover, a high content of trastuzumab (>100 mg/mL) could be loaded into this hydrogel, and trastuzumab demonstrated a sustained release over several weeks through electrostatic attraction. In addition, trastuzumab released from the hydrogel had adequate stability in terms of its structural integrity, binding bioactivity, and antiproliferative effect on BT-474 cells. Pharmacokinetic studies demonstrated that trastuzumab-loaded hydrogel (Her-hydrogel-10, composed of 1.5% γ-PGA-MA, 1.5% 4-arm PEG-SH, and 10 mg/mL trastuzumab) and trastuzumab/Zn-loaded hydrogel (Her/Zn-hydrogel-10, composed of 1.5% γ-PGA-MA, 1.5% 4-arm PEG-SH, 5 mM ZnCl2, and 10 mg/mL trastuzumab) could lower the maximum plasma concentration (Cmax) than the trastuzumab solution. Furthermore, Her/Zn-hydrogel-10 was better able to release trastuzumab in a controlled manner, which was ascribed to electrostatic attraction and formation of trastuzumab/Zn nanocomplexes. In a BT-474 xenograft tumor model, Her-hydrogel-10 had a similar tumor growth-inhibitory effect as that of the trastuzumab solution. By contrast, Her/Zn-hydrogel-10 exhibited a superior tumor growth-inhibitory capability due to the functionality of Zn. This study demonstrated that this hydrogel has potential as a carrier for the local and systemic delivery of proteins and antibodies.
Recently, novel sustained-release formulations of therapeutic antibodies have attracted much attention. However, these formulations should be able to carry a high antibody load owing to the required high dose, and these formulations remain a challenge for practical use. In this study, a novel injectable chemically cross-linked hydrogel was developed for the subcutaneous delivery of trastuzumab. This novel hydrogel possessed ideal characteristics of loading high content of trastuzumab (>100 mg/mL), sustained release of trastuzumab over several weeks, and maintaining adequate stability of trastuzumab. In vivo studies demonstrated that a trastuzumab-loaded hydrogel possessed the ability of controlled release of trastuzumab and maintained antitumor efficacy same as that of trastuzumab. These results implied that a γ-PGA-MA and 4-arm PEG-SH-based hydrogel has great potential in serving as a carrier for the local or systemic delivery of therapeutic proteins or antibodies.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Attraction</subject><subject>Biological activity</subject><subject>Body Weight - drug effects</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Controlled release</subject><subject>Cross-Linking Reagents - chemistry</subject><subject>Crosslinking</subject><subject>Drug Delivery Systems</subject><subject>Drug Liberation</subject><subject>Female</subject><subject>Formulations</subject><subject>Humans</subject><subject>Hydrogels</subject><subject>Hydrogels - chemistry</subject><subject>Immunotherapy</subject><subject>Injectable hydrogels</subject><subject>Injections</subject><subject>Maleimide-modified γ-polyglutamic acid</subject><subject>Maleimides - chemical synthesis</subject><subject>Maleimides - chemistry</subject><subject>Mice, SCID</subject><subject>Monoclonal antibodies</subject><subject>Organic chemistry</subject><subject>Pharmacology</subject><subject>Polyethylene glycol</subject><subject>Polyglutamic Acid - analogs & derivatives</subject><subject>Polyglutamic Acid - chemical synthesis</subject><subject>Polyglutamic Acid - chemistry</subject><subject>Proteins</subject><subject>Rats, Sprague-Dawley</subject><subject>Rheological properties</subject><subject>Rheology</subject><subject>Structural integrity</subject><subject>Sustained release</subject><subject>Targeted cancer therapy</subject><subject>Thiol end-functionalized 4-arm poly(ethylene glycol)</subject><subject>Trastuzumab</subject><subject>Trastuzumab - administration & dosage</subject><subject>Trastuzumab - chemistry</subject><subject>Trastuzumab - pharmacology</subject><subject>Trastuzumab - therapeutic use</subject><subject>Tumors</subject><subject>Xenograft Model Antitumor Assays</subject><subject>Xenografts</subject><subject>Xenotransplantation</subject><subject>Zinc</subject><subject>Zinc chloride</subject><issn>1742-7061</issn><issn>1878-7568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1TAQhSMEoqXwBghZYsMmYRwnsbNBQhU_lSp1A2vLmYy5DklcbKfo9unrksKCRTcee_TN-OiconjNoeLAu_dTZTANzlc18L4CXgGIJ8UpV1KVsu3U03yXTV1K6PhJ8SLGKQOK1-p5cSJyrwMpT4vfFyuLLm0MD7Q4NPN8ZBh8jLNbf9LI3DoRJjPMxA7HMfgfNEdmfWDpQCxuA27JrOS3yEaa3Q2FI_OWpWBi2m63xQws-fwkk9iQz5gYmhUpvCyeWTNHevVQz4rvnz99O_9aXl59uTj_eFmi6CGVRjWolOltn7ULAygbWfdkRgUGLQo7kmiRauSg6rZD243Q1dhaQdRIBeKseLfvvQ7-10Yx6cVFpHneVeuady00IKTI6Nv_0MlvYc3qMtVz0dTQy0w1O_XHpUBWXwe3mHDUHPR9MHrSezD6PhgNXGff89ibh-XbsND4b-hvEhn4sAPZYLpxFHRER9mq0YWcgB69e_yHO30DotA</recordid><startdate>20190301</startdate><enddate>20190301</enddate><creator>Lo, Yu-Wen</creator><creator>Sheu, Ming-Thau</creator><creator>Chiang, Wen-Hsuan</creator><creator>Chiu, Ya-Ling</creator><creator>Tu, Chia-Mu</creator><creator>Wang, Wen-Yu</creator><creator>Wu, Ming-Hsi</creator><creator>Wang, Yu-Cheng</creator><creator>Lu, Maggie</creator><creator>Ho, Hsiu-O</creator><general>Elsevier Ltd</general><general>Elsevier BV</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>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1995-8369</orcidid></search><sort><creationdate>20190301</creationdate><title>In situ chemically crosslinked injectable hydrogels for the subcutaneous delivery of trastuzumab to treat breast cancer</title><author>Lo, Yu-Wen ; Sheu, Ming-Thau ; Chiang, Wen-Hsuan ; Chiu, Ya-Ling ; Tu, Chia-Mu ; Wang, Wen-Yu ; Wu, Ming-Hsi ; Wang, Yu-Cheng ; Lu, Maggie ; Ho, Hsiu-O</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-a84c88a9f90383a0c74729ead80acfc3fde35ce2c108256cf6d062c5f3ee47803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Antibodies</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Attraction</topic><topic>Biological activity</topic><topic>Body Weight - drug effects</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - pathology</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Controlled release</topic><topic>Cross-Linking Reagents - chemistry</topic><topic>Crosslinking</topic><topic>Drug Delivery Systems</topic><topic>Drug Liberation</topic><topic>Female</topic><topic>Formulations</topic><topic>Humans</topic><topic>Hydrogels</topic><topic>Hydrogels - chemistry</topic><topic>Immunotherapy</topic><topic>Injectable hydrogels</topic><topic>Injections</topic><topic>Maleimide-modified γ-polyglutamic acid</topic><topic>Maleimides - chemical synthesis</topic><topic>Maleimides - chemistry</topic><topic>Mice, SCID</topic><topic>Monoclonal antibodies</topic><topic>Organic chemistry</topic><topic>Pharmacology</topic><topic>Polyethylene glycol</topic><topic>Polyglutamic Acid - 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Academic</collection><jtitle>Acta biomaterialia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lo, Yu-Wen</au><au>Sheu, Ming-Thau</au><au>Chiang, Wen-Hsuan</au><au>Chiu, Ya-Ling</au><au>Tu, Chia-Mu</au><au>Wang, Wen-Yu</au><au>Wu, Ming-Hsi</au><au>Wang, Yu-Cheng</au><au>Lu, Maggie</au><au>Ho, Hsiu-O</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In situ chemically crosslinked injectable hydrogels for the subcutaneous delivery of trastuzumab to treat breast cancer</atitle><jtitle>Acta biomaterialia</jtitle><addtitle>Acta Biomater</addtitle><date>2019-03-01</date><risdate>2019</risdate><volume>86</volume><spage>280</spage><epage>290</epage><pages>280-290</pages><issn>1742-7061</issn><eissn>1878-7568</eissn><abstract>[Display omitted]
Recently, novel approaches for the delivery of therapeutic antibodies have attracted much attention, especially sustained release formulations. However, sustained release formulations capable of carrying a high antibody load remain a challenge for practical use. In this study, a novel injectable hydrogel composed of maleimide-modified γ-polyglutamic acid (γ-PGA-MA) and thiol end-functionalized 4-arm poly(ethylene glycol) (4-arm PEG-SH) was developed for the subcutaneous delivery of trastuzumab. γ-PGA-MA and 4-arm PEG-SH formed a hydrogel through thiol-maleimide reactions, which had shear-thinning properties and reversible rheological behaviors. Moreover, a high content of trastuzumab (>100 mg/mL) could be loaded into this hydrogel, and trastuzumab demonstrated a sustained release over several weeks through electrostatic attraction. In addition, trastuzumab released from the hydrogel had adequate stability in terms of its structural integrity, binding bioactivity, and antiproliferative effect on BT-474 cells. Pharmacokinetic studies demonstrated that trastuzumab-loaded hydrogel (Her-hydrogel-10, composed of 1.5% γ-PGA-MA, 1.5% 4-arm PEG-SH, and 10 mg/mL trastuzumab) and trastuzumab/Zn-loaded hydrogel (Her/Zn-hydrogel-10, composed of 1.5% γ-PGA-MA, 1.5% 4-arm PEG-SH, 5 mM ZnCl2, and 10 mg/mL trastuzumab) could lower the maximum plasma concentration (Cmax) than the trastuzumab solution. Furthermore, Her/Zn-hydrogel-10 was better able to release trastuzumab in a controlled manner, which was ascribed to electrostatic attraction and formation of trastuzumab/Zn nanocomplexes. In a BT-474 xenograft tumor model, Her-hydrogel-10 had a similar tumor growth-inhibitory effect as that of the trastuzumab solution. By contrast, Her/Zn-hydrogel-10 exhibited a superior tumor growth-inhibitory capability due to the functionality of Zn. This study demonstrated that this hydrogel has potential as a carrier for the local and systemic delivery of proteins and antibodies.
Recently, novel sustained-release formulations of therapeutic antibodies have attracted much attention. However, these formulations should be able to carry a high antibody load owing to the required high dose, and these formulations remain a challenge for practical use. In this study, a novel injectable chemically cross-linked hydrogel was developed for the subcutaneous delivery of trastuzumab. This novel hydrogel possessed ideal characteristics of loading high content of trastuzumab (>100 mg/mL), sustained release of trastuzumab over several weeks, and maintaining adequate stability of trastuzumab. In vivo studies demonstrated that a trastuzumab-loaded hydrogel possessed the ability of controlled release of trastuzumab and maintained antitumor efficacy same as that of trastuzumab. These results implied that a γ-PGA-MA and 4-arm PEG-SH-based hydrogel has great potential in serving as a carrier for the local or systemic delivery of therapeutic proteins or antibodies.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>30616077</pmid><doi>10.1016/j.actbio.2019.01.003</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-1995-8369</orcidid></addata></record> |
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| ispartof | Acta biomaterialia, 2019-03, Vol.86, p.280-290 |
| issn | 1742-7061 1878-7568 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2165040373 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Antibodies Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Attraction Biological activity Body Weight - drug effects Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - pathology Cell Line, Tumor Cell Proliferation - drug effects Cell Survival - drug effects Controlled release Cross-Linking Reagents - chemistry Crosslinking Drug Delivery Systems Drug Liberation Female Formulations Humans Hydrogels Hydrogels - chemistry Immunotherapy Injectable hydrogels Injections Maleimide-modified γ-polyglutamic acid Maleimides - chemical synthesis Maleimides - chemistry Mice, SCID Monoclonal antibodies Organic chemistry Pharmacology Polyethylene glycol Polyglutamic Acid - analogs & derivatives Polyglutamic Acid - chemical synthesis Polyglutamic Acid - chemistry Proteins Rats, Sprague-Dawley Rheological properties Rheology Structural integrity Sustained release Targeted cancer therapy Thiol end-functionalized 4-arm poly(ethylene glycol) Trastuzumab Trastuzumab - administration & dosage Trastuzumab - chemistry Trastuzumab - pharmacology Trastuzumab - therapeutic use Tumors Xenograft Model Antitumor Assays Xenografts Xenotransplantation Zinc Zinc chloride |
| title | In situ chemically crosslinked injectable hydrogels for the subcutaneous delivery of trastuzumab to treat breast cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-21T14%3A38%3A25IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=In%20situ%20chemically%20crosslinked%20injectable%20hydrogels%20for%20the%20subcutaneous%20delivery%20of%20trastuzumab%20to%20treat%20breast%20cancer&rft.jtitle=Acta%20biomaterialia&rft.au=Lo,%20Yu-Wen&rft.date=2019-03-01&rft.volume=86&rft.spage=280&rft.epage=290&rft.pages=280-290&rft.issn=1742-7061&rft.eissn=1878-7568&rft_id=info:doi/10.1016/j.actbio.2019.01.003&rft_dat=%3Cproquest_cross%3E2165040373%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2191342097&rft_id=info:pmid/30616077&rft_els_id=S1742706119300145&rfr_iscdi=true |