Antimicrobial peptide-grafted PLGA-PEG nanoparticles to fight bacterial wound infections
Wound infection treatment with antimicrobial peptides (AMPs) is still not a reality, due to the loss of activity in vivo . Unlike the conventional strategy of encapsulating AMPs on nanoparticles (NPs) leaving activity dependent on the release profile, this work explores AMP grafting to poly( d , l -...
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| Veröffentlicht in: | Biomaterials science 2023-01, Vol.11 (2), p.499-58 |
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| creator | Ramôa, António Miguel Campos, Filipa Moreira, Luís Teixeira, Cátia Leiro, Victoria Gomes, Paula das Neves, José Martins, M. Cristina L Monteiro, Cláudia |
| description | Wound infection treatment with antimicrobial peptides (AMPs) is still not a reality, due to the loss of activity
in vivo
. Unlike the conventional strategy of encapsulating AMPs on nanoparticles (NPs) leaving activity dependent on the release profile, this work explores AMP grafting to poly(
d
,
l
-lactide-
co
-glycolide)-polyethylene glycol NPs (PLGA-PEG NPs), whereby AMP exposition, infection targeting and immediate action are promoted. NPs are functionalized with MSI-78(4-20), an equipotent and more selective derivative of MSI-78, grafted through a thiol-maleimide (Mal) Michael addition. NPs with different ratios of PLGA-PEG/PLGA-PEG-Mal are produced and characterized, with 40%PLGA-PEG-Mal presenting the best colloidal properties and higher amounts of AMP grafted as shown by surface charge (+8.6 ± 1.8 mV) and AMP quantification (326 μg mL
−1
, corresponding to 16.3 μg of AMP per mg of polymer). NPs maintain the activity of the free AMP with a minimal inhibitory concentration (MIC) of 8-16 μg mL
−1
against
Pseudomonas aeruginosa
, and 16-32 μg mL
−1
against
Staphylococcus aureus
. Moreover, AMP grafting accelerates killing kinetics, from 1-2 h to 15 min for
P. aeruginosa
and from 6-8 h to 0.5-1 h for
S. aureus
. NP activity in a simulated wound fluid is maintained for
S. aureus
and decreases slightly for
P. aeruginosa
. Furthermore, NPs do not demonstrate signs of cytotoxicity at MIC concentrations. Overall, this promising formulation helps unleash the full potential of AMPs for the management of wound infections.
Production and characterization of AMP (MSI-78 (4-20)) grafted PLGA-PEG NPs by optimization of PLGA-PEG/PLGA-PEG-Maleimide ratios. AMP-NPs are biocompatible and demonstrate improved killing kinetics against
S. aureus
and
P. aeruginosa
. |
| doi_str_mv | 10.1039/d2bm01127a |
| format | Article |
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in vivo
. Unlike the conventional strategy of encapsulating AMPs on nanoparticles (NPs) leaving activity dependent on the release profile, this work explores AMP grafting to poly(
d
,
l
-lactide-
co
-glycolide)-polyethylene glycol NPs (PLGA-PEG NPs), whereby AMP exposition, infection targeting and immediate action are promoted. NPs are functionalized with MSI-78(4-20), an equipotent and more selective derivative of MSI-78, grafted through a thiol-maleimide (Mal) Michael addition. NPs with different ratios of PLGA-PEG/PLGA-PEG-Mal are produced and characterized, with 40%PLGA-PEG-Mal presenting the best colloidal properties and higher amounts of AMP grafted as shown by surface charge (+8.6 ± 1.8 mV) and AMP quantification (326 μg mL
−1
, corresponding to 16.3 μg of AMP per mg of polymer). NPs maintain the activity of the free AMP with a minimal inhibitory concentration (MIC) of 8-16 μg mL
−1
against
Pseudomonas aeruginosa
, and 16-32 μg mL
−1
against
Staphylococcus aureus
. Moreover, AMP grafting accelerates killing kinetics, from 1-2 h to 15 min for
P. aeruginosa
and from 6-8 h to 0.5-1 h for
S. aureus
. NP activity in a simulated wound fluid is maintained for
S. aureus
and decreases slightly for
P. aeruginosa
. Furthermore, NPs do not demonstrate signs of cytotoxicity at MIC concentrations. Overall, this promising formulation helps unleash the full potential of AMPs for the management of wound infections.
Production and characterization of AMP (MSI-78 (4-20)) grafted PLGA-PEG NPs by optimization of PLGA-PEG/PLGA-PEG-Maleimide ratios. AMP-NPs are biocompatible and demonstrate improved killing kinetics against
S. aureus
and
P. aeruginosa
.</description><identifier>ISSN: 2047-4830</identifier><identifier>EISSN: 2047-4849</identifier><identifier>DOI: 10.1039/d2bm01127a</identifier><identifier>PMID: 36458466</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Antiinfectives and antibacterials ; Antimicrobial Peptides ; Biocompatibility ; Drug Carriers - chemistry ; Grafting ; Nanoparticles ; Nanoparticles - chemistry ; Particle Size ; Peptides ; Polyethylene glycol ; Polyethylene Glycols - chemistry ; Polymers - chemistry ; Pseudomonas aeruginosa ; Staphylococcus aureus ; Surface charge ; Toxicity</subject><ispartof>Biomaterials science, 2023-01, Vol.11 (2), p.499-58</ispartof><rights>Copyright Royal Society of Chemistry 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3151-6f24c9395723b92e5af5dc22cad0ed581f40407122ceb7c497a3800702062e743</citedby><cites>FETCH-LOGICAL-c3151-6f24c9395723b92e5af5dc22cad0ed581f40407122ceb7c497a3800702062e743</cites><orcidid>0000-0002-6574-4794 ; 0000-0002-6018-4724 ; 0000-0002-2317-2759 ; 0000-0002-5558-0247</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36458466$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ramôa, António Miguel</creatorcontrib><creatorcontrib>Campos, Filipa</creatorcontrib><creatorcontrib>Moreira, Luís</creatorcontrib><creatorcontrib>Teixeira, Cátia</creatorcontrib><creatorcontrib>Leiro, Victoria</creatorcontrib><creatorcontrib>Gomes, Paula</creatorcontrib><creatorcontrib>das Neves, José</creatorcontrib><creatorcontrib>Martins, M. Cristina L</creatorcontrib><creatorcontrib>Monteiro, Cláudia</creatorcontrib><title>Antimicrobial peptide-grafted PLGA-PEG nanoparticles to fight bacterial wound infections</title><title>Biomaterials science</title><addtitle>Biomater Sci</addtitle><description>Wound infection treatment with antimicrobial peptides (AMPs) is still not a reality, due to the loss of activity
in vivo
. Unlike the conventional strategy of encapsulating AMPs on nanoparticles (NPs) leaving activity dependent on the release profile, this work explores AMP grafting to poly(
d
,
l
-lactide-
co
-glycolide)-polyethylene glycol NPs (PLGA-PEG NPs), whereby AMP exposition, infection targeting and immediate action are promoted. NPs are functionalized with MSI-78(4-20), an equipotent and more selective derivative of MSI-78, grafted through a thiol-maleimide (Mal) Michael addition. NPs with different ratios of PLGA-PEG/PLGA-PEG-Mal are produced and characterized, with 40%PLGA-PEG-Mal presenting the best colloidal properties and higher amounts of AMP grafted as shown by surface charge (+8.6 ± 1.8 mV) and AMP quantification (326 μg mL
−1
, corresponding to 16.3 μg of AMP per mg of polymer). NPs maintain the activity of the free AMP with a minimal inhibitory concentration (MIC) of 8-16 μg mL
−1
against
Pseudomonas aeruginosa
, and 16-32 μg mL
−1
against
Staphylococcus aureus
. Moreover, AMP grafting accelerates killing kinetics, from 1-2 h to 15 min for
P. aeruginosa
and from 6-8 h to 0.5-1 h for
S. aureus
. NP activity in a simulated wound fluid is maintained for
S. aureus
and decreases slightly for
P. aeruginosa
. Furthermore, NPs do not demonstrate signs of cytotoxicity at MIC concentrations. Overall, this promising formulation helps unleash the full potential of AMPs for the management of wound infections.
Production and characterization of AMP (MSI-78 (4-20)) grafted PLGA-PEG NPs by optimization of PLGA-PEG/PLGA-PEG-Maleimide ratios. AMP-NPs are biocompatible and demonstrate improved killing kinetics against
S. aureus
and
P. aeruginosa
.</description><subject>Antiinfectives and antibacterials</subject><subject>Antimicrobial Peptides</subject><subject>Biocompatibility</subject><subject>Drug Carriers - chemistry</subject><subject>Grafting</subject><subject>Nanoparticles</subject><subject>Nanoparticles - chemistry</subject><subject>Particle Size</subject><subject>Peptides</subject><subject>Polyethylene glycol</subject><subject>Polyethylene Glycols - chemistry</subject><subject>Polymers - chemistry</subject><subject>Pseudomonas aeruginosa</subject><subject>Staphylococcus aureus</subject><subject>Surface charge</subject><subject>Toxicity</subject><issn>2047-4830</issn><issn>2047-4849</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1LwzAYh4MobsxdvCsFLyJU89WkOc45pzBxBwVvJU3TmdEvkxTxvzdzc4K5vCHvkx9vngBwiuA1gkTcFDivIUKYywMwxJDymKZUHO73BA7A2Lk1DItzARk6BgPCaJJSxobgbdJ4Uxtl29zIKup0502h45WVpddFtFzMJ_FyNo8a2bSdtN6oSrvIt1FpVu8-yqXy2m5ufrZ9U0SmKbXypm3cCTgqZeX0eFdH4PV-9jJ9iBfP88fpZBErghIUsxJTJYhIOCa5wDqRZVIojJUsoC6SFJUUUshRONE5V1RwSdLwEoghw5pTMgKX29zOth-9dj6rjVO6qmSj295lmFNGBEMCBfTiH7pue9uE6QLFWAgVQekIXG2p4MQ5q8uss6aW9itDMNsoz-7w7dOP8kmAz3eRfV7rYo_-Cg7A2RawTu27f39GvgFEe4NX</recordid><startdate>20230117</startdate><enddate>20230117</enddate><creator>Ramôa, António Miguel</creator><creator>Campos, Filipa</creator><creator>Moreira, Luís</creator><creator>Teixeira, Cátia</creator><creator>Leiro, Victoria</creator><creator>Gomes, Paula</creator><creator>das Neves, José</creator><creator>Martins, M. Cristina L</creator><creator>Monteiro, Cláudia</creator><general>Royal Society of Chemistry</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>7SR</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6574-4794</orcidid><orcidid>https://orcid.org/0000-0002-6018-4724</orcidid><orcidid>https://orcid.org/0000-0002-2317-2759</orcidid><orcidid>https://orcid.org/0000-0002-5558-0247</orcidid></search><sort><creationdate>20230117</creationdate><title>Antimicrobial peptide-grafted PLGA-PEG nanoparticles to fight bacterial wound infections</title><author>Ramôa, António Miguel ; Campos, Filipa ; Moreira, Luís ; Teixeira, Cátia ; Leiro, Victoria ; Gomes, Paula ; das Neves, José ; Martins, M. Cristina L ; Monteiro, Cláudia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3151-6f24c9395723b92e5af5dc22cad0ed581f40407122ceb7c497a3800702062e743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Antiinfectives and antibacterials</topic><topic>Antimicrobial Peptides</topic><topic>Biocompatibility</topic><topic>Drug Carriers - chemistry</topic><topic>Grafting</topic><topic>Nanoparticles</topic><topic>Nanoparticles - chemistry</topic><topic>Particle Size</topic><topic>Peptides</topic><topic>Polyethylene glycol</topic><topic>Polyethylene Glycols - chemistry</topic><topic>Polymers - chemistry</topic><topic>Pseudomonas aeruginosa</topic><topic>Staphylococcus aureus</topic><topic>Surface charge</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ramôa, António Miguel</creatorcontrib><creatorcontrib>Campos, Filipa</creatorcontrib><creatorcontrib>Moreira, Luís</creatorcontrib><creatorcontrib>Teixeira, Cátia</creatorcontrib><creatorcontrib>Leiro, Victoria</creatorcontrib><creatorcontrib>Gomes, Paula</creatorcontrib><creatorcontrib>das Neves, José</creatorcontrib><creatorcontrib>Martins, M. Cristina L</creatorcontrib><creatorcontrib>Monteiro, Cláudia</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>MEDLINE - Academic</collection><jtitle>Biomaterials science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ramôa, António Miguel</au><au>Campos, Filipa</au><au>Moreira, Luís</au><au>Teixeira, Cátia</au><au>Leiro, Victoria</au><au>Gomes, Paula</au><au>das Neves, José</au><au>Martins, M. Cristina L</au><au>Monteiro, Cláudia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antimicrobial peptide-grafted PLGA-PEG nanoparticles to fight bacterial wound infections</atitle><jtitle>Biomaterials science</jtitle><addtitle>Biomater Sci</addtitle><date>2023-01-17</date><risdate>2023</risdate><volume>11</volume><issue>2</issue><spage>499</spage><epage>58</epage><pages>499-58</pages><issn>2047-4830</issn><eissn>2047-4849</eissn><abstract>Wound infection treatment with antimicrobial peptides (AMPs) is still not a reality, due to the loss of activity
in vivo
. Unlike the conventional strategy of encapsulating AMPs on nanoparticles (NPs) leaving activity dependent on the release profile, this work explores AMP grafting to poly(
d
,
l
-lactide-
co
-glycolide)-polyethylene glycol NPs (PLGA-PEG NPs), whereby AMP exposition, infection targeting and immediate action are promoted. NPs are functionalized with MSI-78(4-20), an equipotent and more selective derivative of MSI-78, grafted through a thiol-maleimide (Mal) Michael addition. NPs with different ratios of PLGA-PEG/PLGA-PEG-Mal are produced and characterized, with 40%PLGA-PEG-Mal presenting the best colloidal properties and higher amounts of AMP grafted as shown by surface charge (+8.6 ± 1.8 mV) and AMP quantification (326 μg mL
−1
, corresponding to 16.3 μg of AMP per mg of polymer). NPs maintain the activity of the free AMP with a minimal inhibitory concentration (MIC) of 8-16 μg mL
−1
against
Pseudomonas aeruginosa
, and 16-32 μg mL
−1
against
Staphylococcus aureus
. Moreover, AMP grafting accelerates killing kinetics, from 1-2 h to 15 min for
P. aeruginosa
and from 6-8 h to 0.5-1 h for
S. aureus
. NP activity in a simulated wound fluid is maintained for
S. aureus
and decreases slightly for
P. aeruginosa
. Furthermore, NPs do not demonstrate signs of cytotoxicity at MIC concentrations. Overall, this promising formulation helps unleash the full potential of AMPs for the management of wound infections.
Production and characterization of AMP (MSI-78 (4-20)) grafted PLGA-PEG NPs by optimization of PLGA-PEG/PLGA-PEG-Maleimide ratios. AMP-NPs are biocompatible and demonstrate improved killing kinetics against
S. aureus
and
P. aeruginosa
.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>36458466</pmid><doi>10.1039/d2bm01127a</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-6574-4794</orcidid><orcidid>https://orcid.org/0000-0002-6018-4724</orcidid><orcidid>https://orcid.org/0000-0002-2317-2759</orcidid><orcidid>https://orcid.org/0000-0002-5558-0247</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Biomaterials science, 2023-01, Vol.11 (2), p.499-58 |
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| language | eng |
| recordid | cdi_proquest_journals_2766070910 |
| source | MEDLINE; Royal Society Of Chemistry Journals 2008- |
| subjects | Antiinfectives and antibacterials Antimicrobial Peptides Biocompatibility Drug Carriers - chemistry Grafting Nanoparticles Nanoparticles - chemistry Particle Size Peptides Polyethylene glycol Polyethylene Glycols - chemistry Polymers - chemistry Pseudomonas aeruginosa Staphylococcus aureus Surface charge Toxicity |
| title | Antimicrobial peptide-grafted PLGA-PEG nanoparticles to fight bacterial wound infections |
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