Improved delivery of PLGA microparticles and microparticle-cell scaffolds in clinical needle gauges using modified viscosity formulations
[Display omitted] Polymer microparticles are widely used as acellular drug delivery platforms in regenerative medicine, and have emerging potential as cellular scaffolds for therapeutic cell delivery. In the clinic, PLGA microparticles are typically administered intramuscularly or subcutaneously, wi...
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Veröffentlicht in: | International journal of pharmaceutics 2018-07, Vol.546 (1-2), p.272-278 |
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container_title | International journal of pharmaceutics |
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creator | Qutachi, Omar Wright, Emma J. Bray, Gemma Hamid, Omar A. Rose, Felicity R.A.J. Shakesheff, Kevin M. Delcassian, Derfogail |
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Polymer microparticles are widely used as acellular drug delivery platforms in regenerative medicine, and have emerging potential as cellular scaffolds for therapeutic cell delivery. In the clinic, PLGA microparticles are typically administered intramuscularly or subcutaneously, with the clinician and clinical application site determining the precise needle gauge used for delivery. Here, we explored the role of needle diameter in microparticle delivery yield, and develop a modified viscosity formulation to improve microparticle delivery across a range of clinically relevant needle diameters. We have identified an optimal biocompatible formulation containing 0.25% pluronic F127 and 0.25% carboxymethyl cellulose, which can increase delivery payload to 520% across needle gauges 21–30G, and note that needle diameter impacts delivery efficacy. We use this formulation to increase the delivery yield of PLGA microparticles, and separately, PLGA-cell scaffolds supporting viable mesenchymal stem cells (MSCs), demonstrating the first in vitro delivery of this cell scaffold system. Together, these results highlight an optimal formulation for the delivery of microparticle and microparticle-cell scaffolds, and illustrate how careful choice of delivery formulation and needle size can dramatically impact delivery payload. |
doi_str_mv | 10.1016/j.ijpharm.2018.05.025 |
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Polymer microparticles are widely used as acellular drug delivery platforms in regenerative medicine, and have emerging potential as cellular scaffolds for therapeutic cell delivery. In the clinic, PLGA microparticles are typically administered intramuscularly or subcutaneously, with the clinician and clinical application site determining the precise needle gauge used for delivery. Here, we explored the role of needle diameter in microparticle delivery yield, and develop a modified viscosity formulation to improve microparticle delivery across a range of clinically relevant needle diameters. We have identified an optimal biocompatible formulation containing 0.25% pluronic F127 and 0.25% carboxymethyl cellulose, which can increase delivery payload to 520% across needle gauges 21–30G, and note that needle diameter impacts delivery efficacy. We use this formulation to increase the delivery yield of PLGA microparticles, and separately, PLGA-cell scaffolds supporting viable mesenchymal stem cells (MSCs), demonstrating the first in vitro delivery of this cell scaffold system. Together, these results highlight an optimal formulation for the delivery of microparticle and microparticle-cell scaffolds, and illustrate how careful choice of delivery formulation and needle size can dramatically impact delivery payload.</description><identifier>ISSN: 0378-5173</identifier><identifier>EISSN: 1873-3476</identifier><identifier>DOI: 10.1016/j.ijpharm.2018.05.025</identifier><identifier>PMID: 29753905</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Carboxymethylcellulose Sodium - administration & dosage ; Carboxymethylcellulose Sodium - chemistry ; Cell particle scaffolds ; Cell Survival ; Cell- and Tissue-Based Therapy ; High viscosity formulation ; Humans ; Lactic Acid - administration & dosage ; Lactic Acid - chemistry ; Mesenchymal Stromal Cells ; Microparticle delivery ; Needle gauge ; Needles ; Poloxamer - administration & dosage ; Poloxamer - chemistry ; Polyglycolic Acid - administration & dosage ; Polyglycolic Acid - chemistry ; Viscosity</subject><ispartof>International journal of pharmaceutics, 2018-07, Vol.546 (1-2), p.272-278</ispartof><rights>2018</rights><rights>Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-f6f26adf4ba94f2159840af230839adaf6fe89cf4e9ceaafc1aa43e0b84a94043</citedby><cites>FETCH-LOGICAL-c412t-f6f26adf4ba94f2159840af230839adaf6fe89cf4e9ceaafc1aa43e0b84a94043</cites><orcidid>0000-0002-8030-7672</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0378517318303235$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29753905$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qutachi, Omar</creatorcontrib><creatorcontrib>Wright, Emma J.</creatorcontrib><creatorcontrib>Bray, Gemma</creatorcontrib><creatorcontrib>Hamid, Omar A.</creatorcontrib><creatorcontrib>Rose, Felicity R.A.J.</creatorcontrib><creatorcontrib>Shakesheff, Kevin M.</creatorcontrib><creatorcontrib>Delcassian, Derfogail</creatorcontrib><title>Improved delivery of PLGA microparticles and microparticle-cell scaffolds in clinical needle gauges using modified viscosity formulations</title><title>International journal of pharmaceutics</title><addtitle>Int J Pharm</addtitle><description>[Display omitted]
Polymer microparticles are widely used as acellular drug delivery platforms in regenerative medicine, and have emerging potential as cellular scaffolds for therapeutic cell delivery. In the clinic, PLGA microparticles are typically administered intramuscularly or subcutaneously, with the clinician and clinical application site determining the precise needle gauge used for delivery. Here, we explored the role of needle diameter in microparticle delivery yield, and develop a modified viscosity formulation to improve microparticle delivery across a range of clinically relevant needle diameters. We have identified an optimal biocompatible formulation containing 0.25% pluronic F127 and 0.25% carboxymethyl cellulose, which can increase delivery payload to 520% across needle gauges 21–30G, and note that needle diameter impacts delivery efficacy. We use this formulation to increase the delivery yield of PLGA microparticles, and separately, PLGA-cell scaffolds supporting viable mesenchymal stem cells (MSCs), demonstrating the first in vitro delivery of this cell scaffold system. Together, these results highlight an optimal formulation for the delivery of microparticle and microparticle-cell scaffolds, and illustrate how careful choice of delivery formulation and needle size can dramatically impact delivery payload.</description><subject>Carboxymethylcellulose Sodium - administration & dosage</subject><subject>Carboxymethylcellulose Sodium - chemistry</subject><subject>Cell particle scaffolds</subject><subject>Cell Survival</subject><subject>Cell- and Tissue-Based Therapy</subject><subject>High viscosity formulation</subject><subject>Humans</subject><subject>Lactic Acid - administration & dosage</subject><subject>Lactic Acid - chemistry</subject><subject>Mesenchymal Stromal Cells</subject><subject>Microparticle delivery</subject><subject>Needle gauge</subject><subject>Needles</subject><subject>Poloxamer - administration & dosage</subject><subject>Poloxamer - chemistry</subject><subject>Polyglycolic Acid - administration & dosage</subject><subject>Polyglycolic Acid - chemistry</subject><subject>Viscosity</subject><issn>0378-5173</issn><issn>1873-3476</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUctuFDEQtBCIbAKfAPKRywx-zeuEoigkkVaCQ3K2eu324pVnvNgzK-0n8Nc42g1STpxa6q7q6uoi5BNnNWe8_bqr_W7_C9JYC8b7mjU1E80bsuJ9JyupuvYtWTHZ9VXDO3lBLnPeMcZaweV7ciGGrpEDa1bkz8O4T_GAlloM_oDpSKOjP9d313T0JsU9pNmbgJnCZF-3KoMh0GzAuRhspn6iJvjJGwh0QrQB6RaWbaEu2U9bOkbrnS9KB59NzH4-UhfTuASYfZzyB_LOQcj48VyvyNP328eb-2r94-7h5npdGcXFXLnWiRasUxsYlBO8GXrFwAnJejmAhTLHfjBO4WAQwBkOoCSyTa8KgSl5Rb6c9hbfvxfMsx7LPcUKTBiXrAWTfcc5G9oCbU7Q4jrnhE7vkx8hHTVn-jkFvdPnFPRzCpo1uqRQeJ_PEstmRPuP9fL2Avh2AmAxevCYdDYeJ4PWJzSzttH_R-IvMouf5w</recordid><startdate>20180730</startdate><enddate>20180730</enddate><creator>Qutachi, Omar</creator><creator>Wright, Emma J.</creator><creator>Bray, Gemma</creator><creator>Hamid, Omar A.</creator><creator>Rose, Felicity R.A.J.</creator><creator>Shakesheff, Kevin M.</creator><creator>Delcassian, Derfogail</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><orcidid>https://orcid.org/0000-0002-8030-7672</orcidid></search><sort><creationdate>20180730</creationdate><title>Improved delivery of PLGA microparticles and microparticle-cell scaffolds in clinical needle gauges using modified viscosity formulations</title><author>Qutachi, Omar ; Wright, Emma J. ; Bray, Gemma ; Hamid, Omar A. ; Rose, Felicity R.A.J. ; Shakesheff, Kevin M. ; Delcassian, Derfogail</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-f6f26adf4ba94f2159840af230839adaf6fe89cf4e9ceaafc1aa43e0b84a94043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Carboxymethylcellulose Sodium - administration & dosage</topic><topic>Carboxymethylcellulose Sodium - chemistry</topic><topic>Cell particle scaffolds</topic><topic>Cell Survival</topic><topic>Cell- and Tissue-Based Therapy</topic><topic>High viscosity formulation</topic><topic>Humans</topic><topic>Lactic Acid - administration & dosage</topic><topic>Lactic Acid - chemistry</topic><topic>Mesenchymal Stromal Cells</topic><topic>Microparticle delivery</topic><topic>Needle gauge</topic><topic>Needles</topic><topic>Poloxamer - administration & dosage</topic><topic>Poloxamer - chemistry</topic><topic>Polyglycolic Acid - administration & dosage</topic><topic>Polyglycolic Acid - chemistry</topic><topic>Viscosity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qutachi, Omar</creatorcontrib><creatorcontrib>Wright, Emma J.</creatorcontrib><creatorcontrib>Bray, Gemma</creatorcontrib><creatorcontrib>Hamid, Omar A.</creatorcontrib><creatorcontrib>Rose, Felicity R.A.J.</creatorcontrib><creatorcontrib>Shakesheff, Kevin M.</creatorcontrib><creatorcontrib>Delcassian, Derfogail</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>Qutachi, Omar</au><au>Wright, Emma J.</au><au>Bray, Gemma</au><au>Hamid, Omar A.</au><au>Rose, Felicity R.A.J.</au><au>Shakesheff, Kevin M.</au><au>Delcassian, Derfogail</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Improved delivery of PLGA microparticles and microparticle-cell scaffolds in clinical needle gauges using modified viscosity formulations</atitle><jtitle>International journal of pharmaceutics</jtitle><addtitle>Int J Pharm</addtitle><date>2018-07-30</date><risdate>2018</risdate><volume>546</volume><issue>1-2</issue><spage>272</spage><epage>278</epage><pages>272-278</pages><issn>0378-5173</issn><eissn>1873-3476</eissn><abstract>[Display omitted]
Polymer microparticles are widely used as acellular drug delivery platforms in regenerative medicine, and have emerging potential as cellular scaffolds for therapeutic cell delivery. In the clinic, PLGA microparticles are typically administered intramuscularly or subcutaneously, with the clinician and clinical application site determining the precise needle gauge used for delivery. Here, we explored the role of needle diameter in microparticle delivery yield, and develop a modified viscosity formulation to improve microparticle delivery across a range of clinically relevant needle diameters. We have identified an optimal biocompatible formulation containing 0.25% pluronic F127 and 0.25% carboxymethyl cellulose, which can increase delivery payload to 520% across needle gauges 21–30G, and note that needle diameter impacts delivery efficacy. We use this formulation to increase the delivery yield of PLGA microparticles, and separately, PLGA-cell scaffolds supporting viable mesenchymal stem cells (MSCs), demonstrating the first in vitro delivery of this cell scaffold system. Together, these results highlight an optimal formulation for the delivery of microparticle and microparticle-cell scaffolds, and illustrate how careful choice of delivery formulation and needle size can dramatically impact delivery payload.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>29753905</pmid><doi>10.1016/j.ijpharm.2018.05.025</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-8030-7672</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Carboxymethylcellulose Sodium - administration & dosage Carboxymethylcellulose Sodium - chemistry Cell particle scaffolds Cell Survival Cell- and Tissue-Based Therapy High viscosity formulation Humans Lactic Acid - administration & dosage Lactic Acid - chemistry Mesenchymal Stromal Cells Microparticle delivery Needle gauge Needles Poloxamer - administration & dosage Poloxamer - chemistry Polyglycolic Acid - administration & dosage Polyglycolic Acid - chemistry Viscosity |
title | Improved delivery of PLGA microparticles and microparticle-cell scaffolds in clinical needle gauges using modified viscosity formulations |
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