Kinetic control of Phytic acid/Lixisenatide/Fe (III) ternary nanoparticles assembly process for sustained peptide release
[Display omitted] The preferable choice of sustained peptide delivery systems is generally polymer-based microspheres in which their large particle size, wide size distribution, low drug encapsulation efficacy, poor colloidal stability, and undesirable burst release eventually hinder their clinical...
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| Veröffentlicht in: | International journal of pharmaceutics 2022-01, Vol.611, p.121317-121317, Article 121317 |
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| container_title | International journal of pharmaceutics |
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| creator | Wang, Yanan Song, Xinyu Zhuang, Liwei Lang, Haifeng Yu, Liangmin Yan, Xuefeng He, Zhiyu |
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The preferable choice of sustained peptide delivery systems is generally polymer-based microspheres in which their large particle size, wide size distribution, low drug encapsulation efficacy, poor colloidal stability, and undesirable burst release eventually hinder their clinical translation. In this study, a nanoscale ternary Lixisenatide (Lix) sustained delivery system based on strong multivalent interactions (electrostatic and coordination complexation) among small molecular phytic acid (PA), Lix and Fe3+ was developed. Flash nanocomplexation (FNC) was utilized to facilitate the rapid and efficient mixing of the three components and kinetically control the assembly process that enabled dynamic balance of two competitive chemical reactions with different kinetic rates (slow chemical reaction of PA/Lix and fast chemical reaction of PA/Fe3+) to generate structural uniform ternary nanoparticles and avoid heterogeneous complexes. By tuning the mixing conditions (i.e., flow rate, mass ratio, concentration, pH value, etc.), the ternary PA/Lix/Fe3+ nanoparticles were assembled with reproducible production in a manner of high uniformity and scalability, achieving small size (∼50 nm), uniform composition (PDI: ∼0.12), favourable colloidal stability, high encapsulation efficiency (∼100%), and tunable drug release kinetics. The optimized formulation exhibited a minor Lix release ( |
| doi_str_mv | 10.1016/j.ijpharm.2021.121317 |
| format | Article |
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The preferable choice of sustained peptide delivery systems is generally polymer-based microspheres in which their large particle size, wide size distribution, low drug encapsulation efficacy, poor colloidal stability, and undesirable burst release eventually hinder their clinical translation. In this study, a nanoscale ternary Lixisenatide (Lix) sustained delivery system based on strong multivalent interactions (electrostatic and coordination complexation) among small molecular phytic acid (PA), Lix and Fe3+ was developed. Flash nanocomplexation (FNC) was utilized to facilitate the rapid and efficient mixing of the three components and kinetically control the assembly process that enabled dynamic balance of two competitive chemical reactions with different kinetic rates (slow chemical reaction of PA/Lix and fast chemical reaction of PA/Fe3+) to generate structural uniform ternary nanoparticles and avoid heterogeneous complexes. By tuning the mixing conditions (i.e., flow rate, mass ratio, concentration, pH value, etc.), the ternary PA/Lix/Fe3+ nanoparticles were assembled with reproducible production in a manner of high uniformity and scalability, achieving small size (∼50 nm), uniform composition (PDI: ∼0.12), favourable colloidal stability, high encapsulation efficiency (∼100%), and tunable drug release kinetics. The optimized formulation exhibited a minor Lix release (<20%) in the first day and extended peptide release period over 8 days. Unexpectedly, upon a single injection administration, the as-prepared formulation (600 μg/kg) rapidly brought the high BGL (∼30 mmol/L) back to normal range (<10 mmol/L) within the initial 6 h and achieved a 180 h glycemic control in T2D mouse model. Moreover, this sustained peptide delivery system demonstrated a repeatable hypoglycemic effects and significantly suppressed the pathological damage of major organs following multiple injection. This sustained peptide delivery system with aqueous, facile and reproducible preparation process possesses good biocompatibility, tunable release kinetics, and prolonged hypoglycemic effects, portending its great translational potential in the chronic disease treatment.</description><identifier>ISSN: 0378-5173</identifier><identifier>EISSN: 1873-3476</identifier><identifier>DOI: 10.1016/j.ijpharm.2021.121317</identifier><identifier>PMID: 34838624</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Flash nanocomplexation ; Kinetic control ; Kinetics ; Lixisenatide ; Mice ; Nanoparticles ; Peptides ; Phytic Acid ; Sustained release ; Type 2 diabetes</subject><ispartof>International journal of pharmaceutics, 2022-01, Vol.611, p.121317-121317, Article 121317</ispartof><rights>2021 Elsevier B.V.</rights><rights>Copyright © 2021 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-4770fbee98db7fae929c71a003802c12a1397b46fc139f8fdd23514d0358ae9c3</citedby><cites>FETCH-LOGICAL-c365t-4770fbee98db7fae929c71a003802c12a1397b46fc139f8fdd23514d0358ae9c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ijpharm.2021.121317$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34838624$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Yanan</creatorcontrib><creatorcontrib>Song, Xinyu</creatorcontrib><creatorcontrib>Zhuang, Liwei</creatorcontrib><creatorcontrib>Lang, Haifeng</creatorcontrib><creatorcontrib>Yu, Liangmin</creatorcontrib><creatorcontrib>Yan, Xuefeng</creatorcontrib><creatorcontrib>He, Zhiyu</creatorcontrib><title>Kinetic control of Phytic acid/Lixisenatide/Fe (III) ternary nanoparticles assembly process for sustained peptide release</title><title>International journal of pharmaceutics</title><addtitle>Int J Pharm</addtitle><description>[Display omitted]
The preferable choice of sustained peptide delivery systems is generally polymer-based microspheres in which their large particle size, wide size distribution, low drug encapsulation efficacy, poor colloidal stability, and undesirable burst release eventually hinder their clinical translation. In this study, a nanoscale ternary Lixisenatide (Lix) sustained delivery system based on strong multivalent interactions (electrostatic and coordination complexation) among small molecular phytic acid (PA), Lix and Fe3+ was developed. Flash nanocomplexation (FNC) was utilized to facilitate the rapid and efficient mixing of the three components and kinetically control the assembly process that enabled dynamic balance of two competitive chemical reactions with different kinetic rates (slow chemical reaction of PA/Lix and fast chemical reaction of PA/Fe3+) to generate structural uniform ternary nanoparticles and avoid heterogeneous complexes. By tuning the mixing conditions (i.e., flow rate, mass ratio, concentration, pH value, etc.), the ternary PA/Lix/Fe3+ nanoparticles were assembled with reproducible production in a manner of high uniformity and scalability, achieving small size (∼50 nm), uniform composition (PDI: ∼0.12), favourable colloidal stability, high encapsulation efficiency (∼100%), and tunable drug release kinetics. The optimized formulation exhibited a minor Lix release (<20%) in the first day and extended peptide release period over 8 days. Unexpectedly, upon a single injection administration, the as-prepared formulation (600 μg/kg) rapidly brought the high BGL (∼30 mmol/L) back to normal range (<10 mmol/L) within the initial 6 h and achieved a 180 h glycemic control in T2D mouse model. Moreover, this sustained peptide delivery system demonstrated a repeatable hypoglycemic effects and significantly suppressed the pathological damage of major organs following multiple injection. This sustained peptide delivery system with aqueous, facile and reproducible preparation process possesses good biocompatibility, tunable release kinetics, and prolonged hypoglycemic effects, portending its great translational potential in the chronic disease treatment.</description><subject>Animals</subject><subject>Flash nanocomplexation</subject><subject>Kinetic control</subject><subject>Kinetics</subject><subject>Lixisenatide</subject><subject>Mice</subject><subject>Nanoparticles</subject><subject>Peptides</subject><subject>Phytic Acid</subject><subject>Sustained release</subject><subject>Type 2 diabetes</subject><issn>0378-5173</issn><issn>1873-3476</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1v2zAMhoViRZO1_QkbdOwOTvRhW85pGIp1DRqgPWxnQZYoRIFteaJTNP--CpLt2hMF4iFf8SHkC2cLzni93C3Cbtya1C8EE3zBBZdcXZA5b5QsZKnqT2TOpGqKiis5I58Rd4yxOmNXZCbLRja1KOfk8BQGmIKlNg5Tih2Nnr5sD8eOscEtN-EtIAxmCg6WD0Dv1uv1NzpBGkw60MEMcTQp0x0gNYjQt92BjilaQKQ-Jop7nEzOcHSE8biFJujAINyQS286hNtzvSZ_Hn7-vn8sNs-_1vc_NoWVdTUVpVLMtwCrxrXKG1iJlVXcMCYbJiwXhsuVasva2_zwjXdOyIqXjsmqybSV1-TutDf_6u8ecNJ9QAtdZwaIe9SiZmWpmJQ8o9UJtSkiJvB6TKHPh2rO9NG63umzdX20rk_W89zXc8S-7cH9n_qnOQPfTwDkQ18DJI02wGDBhQR20i6GDyLeAZhJl2Q</recordid><startdate>20220105</startdate><enddate>20220105</enddate><creator>Wang, Yanan</creator><creator>Song, Xinyu</creator><creator>Zhuang, Liwei</creator><creator>Lang, Haifeng</creator><creator>Yu, Liangmin</creator><creator>Yan, Xuefeng</creator><creator>He, Zhiyu</creator><general>Elsevier B.V</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>7X8</scope></search><sort><creationdate>20220105</creationdate><title>Kinetic control of Phytic acid/Lixisenatide/Fe (III) ternary nanoparticles assembly process for sustained peptide release</title><author>Wang, Yanan ; Song, Xinyu ; Zhuang, Liwei ; Lang, Haifeng ; Yu, Liangmin ; Yan, Xuefeng ; He, Zhiyu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-4770fbee98db7fae929c71a003802c12a1397b46fc139f8fdd23514d0358ae9c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Flash nanocomplexation</topic><topic>Kinetic control</topic><topic>Kinetics</topic><topic>Lixisenatide</topic><topic>Mice</topic><topic>Nanoparticles</topic><topic>Peptides</topic><topic>Phytic Acid</topic><topic>Sustained release</topic><topic>Type 2 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Yanan</creatorcontrib><creatorcontrib>Song, Xinyu</creatorcontrib><creatorcontrib>Zhuang, Liwei</creatorcontrib><creatorcontrib>Lang, Haifeng</creatorcontrib><creatorcontrib>Yu, Liangmin</creatorcontrib><creatorcontrib>Yan, Xuefeng</creatorcontrib><creatorcontrib>He, Zhiyu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of pharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Yanan</au><au>Song, Xinyu</au><au>Zhuang, Liwei</au><au>Lang, Haifeng</au><au>Yu, Liangmin</au><au>Yan, Xuefeng</au><au>He, Zhiyu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Kinetic control of Phytic acid/Lixisenatide/Fe (III) ternary nanoparticles assembly process for sustained peptide release</atitle><jtitle>International journal of pharmaceutics</jtitle><addtitle>Int J Pharm</addtitle><date>2022-01-05</date><risdate>2022</risdate><volume>611</volume><spage>121317</spage><epage>121317</epage><pages>121317-121317</pages><artnum>121317</artnum><issn>0378-5173</issn><eissn>1873-3476</eissn><abstract>[Display omitted]
The preferable choice of sustained peptide delivery systems is generally polymer-based microspheres in which their large particle size, wide size distribution, low drug encapsulation efficacy, poor colloidal stability, and undesirable burst release eventually hinder their clinical translation. In this study, a nanoscale ternary Lixisenatide (Lix) sustained delivery system based on strong multivalent interactions (electrostatic and coordination complexation) among small molecular phytic acid (PA), Lix and Fe3+ was developed. Flash nanocomplexation (FNC) was utilized to facilitate the rapid and efficient mixing of the three components and kinetically control the assembly process that enabled dynamic balance of two competitive chemical reactions with different kinetic rates (slow chemical reaction of PA/Lix and fast chemical reaction of PA/Fe3+) to generate structural uniform ternary nanoparticles and avoid heterogeneous complexes. By tuning the mixing conditions (i.e., flow rate, mass ratio, concentration, pH value, etc.), the ternary PA/Lix/Fe3+ nanoparticles were assembled with reproducible production in a manner of high uniformity and scalability, achieving small size (∼50 nm), uniform composition (PDI: ∼0.12), favourable colloidal stability, high encapsulation efficiency (∼100%), and tunable drug release kinetics. The optimized formulation exhibited a minor Lix release (<20%) in the first day and extended peptide release period over 8 days. Unexpectedly, upon a single injection administration, the as-prepared formulation (600 μg/kg) rapidly brought the high BGL (∼30 mmol/L) back to normal range (<10 mmol/L) within the initial 6 h and achieved a 180 h glycemic control in T2D mouse model. Moreover, this sustained peptide delivery system demonstrated a repeatable hypoglycemic effects and significantly suppressed the pathological damage of major organs following multiple injection. This sustained peptide delivery system with aqueous, facile and reproducible preparation process possesses good biocompatibility, tunable release kinetics, and prolonged hypoglycemic effects, portending its great translational potential in the chronic disease treatment.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>34838624</pmid><doi>10.1016/j.ijpharm.2021.121317</doi><tpages>1</tpages></addata></record> |
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| subjects | Animals Flash nanocomplexation Kinetic control Kinetics Lixisenatide Mice Nanoparticles Peptides Phytic Acid Sustained release Type 2 diabetes |
| title | Kinetic control of Phytic acid/Lixisenatide/Fe (III) ternary nanoparticles assembly process for sustained peptide release |
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