Enhancement of polymer thermoresponsiveness and drug delivery across biological barriers by addition of small molecules

Thermoresponsive polymers that undergo sol–gel transitions in the physiological temperature range have been widely used in biomedical applications. However, some commercially and clinically available thermoresponsive materials, particularly poloxamer 407 (P407), have the significant drawback of insu...

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Published inHeliyon Vol. 9; no. 6; p. e16923
Main Authors Zhang, Zipei, Li, Xiyu, Do, Changwoo, Kohane, Daniel S.
Format Journal Article
LanguageEnglish
Published England Elsevier Ltd 01.06.2023
Elsevier
Subjects
Chemical permeation enhancer
Gelation
Otitis media
Thermoresponsive polymers
Tympanic membrane
Chemical permeation enhancer
Otitis media
Thermoresponsive polymers
Tympanic membrane
Gelation
Online AccessGet full text

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Abstract Thermoresponsive polymers that undergo sol–gel transitions in the physiological temperature range have been widely used in biomedical applications. However, some commercially and clinically available thermoresponsive materials, particularly poloxamer 407 (P407), have the significant drawback of insufficient gel strength, which limit their performance. Furthermore, co-delivery with some small molecules, including chemical permeation enhancers (CPEs) can further impair the physical properties of P407. Here, we have developed a thermoresponsive platform by combination of CPEs with the poloxamer P188 to enable gelation at physiological temperatures and enhance gel strength. P188 gels at 60 °C, which is far above the physiological range. In combination with limonene (LIM) and sodium dodecyl sulfate (SDS), P188 gels at ∼25 °C, a temperature that in useful for biomedical applications. Gelation behavior was studied by small angle neutron scattering (SANS) experiments, which identified micelle-to-cubic mesophase transitions with increasing temperature. Analysis of the SANS intensities revealed that P188 micelles became larger as LIM or SDS molecules were incorporated, making it easier to form a micellar gel structure. P188-3CPE (i.e., 2% LIM, 1% SDS and 0.5% bupivacaine (BUP)) had low viscosity at room temperature, facilitating administration, but rapidly gelled at body temperature. P188-3CPE enabled the flux of the antibiotic ciprofloxacin across the TM and completely eradicated otitis media from nontypable Haemophilus influenzae (NTHi) in chinchillas after a single administration.
AbstractList Thermoresponsive polymers that undergo sol–gel transitions in the physiological temperature range have been widely used in biomedical applications. However, some commercially and clinically available thermoresponsive materials, particularly poloxamer 407 (P407), have the significant drawback of insufficient gel strength, which limit their performance. Furthermore, co-delivery with some small molecules, including chemical permeation enhancers (CPEs) can further impair the physical properties of P407. Here, we have developed a thermoresponsive platform by combination of CPEs with the poloxamer P188 to enable gelation at physiological temperatures and enhance gel strength. P188 gels at 60 °C, which is far above the physiological range. In combination with limonene (LIM) and sodium dodecyl sulfate (SDS), P188 gels at ∼25 °C, a temperature that in useful for biomedical applications. Gelation behavior was studied by small angle neutron scattering (SANS) experiments, which identified micelle-to-cubic mesophase transitions with increasing temperature. Analysis of the SANS intensities revealed that P188 micelles became larger as LIM or SDS molecules were incorporated, making it easier to form a micellar gel structure. P188-3CPE (i.e., 2% LIM, 1% SDS and 0.5% bupivacaine (BUP)) had low viscosity at room temperature, facilitating administration, but rapidly gelled at body temperature. P188-3CPE enabled the flux of the antibiotic ciprofloxacin across the TM and completely eradicated otitis media from nontypable Haemophilus influenzae (NTHi) in chinchillas after a single administration.
Thermoresponsive polymers that undergo sol-gel transitions in the physiological temperature range have been widely used in biomedical applications. However, some commercially and clinically available thermoresponsive materials, particularly poloxamer 407 (P407), have the significant drawback of insufficient gel strength, which limit their performance. Furthermore, co-delivery with some small molecules, including chemical permeation enhancers (CPEs) can further impair the physical properties of P407. Here, we have developed a thermoresponsive platform by combination of CPEs with the poloxamer P188 to enable gelation at physiological temperatures and enhance gel strength. P188 gels at 60 °C, which is far above the physiological range. In combination with limonene (LIM) and sodium dodecyl sulfate (SDS), P188 gels at ∼25 °C, a temperature that in useful for biomedical applications. Gelation behavior was studied by small angle neutron scattering (SANS) experiments, which identified micelle-to-cubic mesophase transitions with increasing temperature. Analysis of the SANS intensities revealed that P188 micelles became larger as LIM or SDS molecules were incorporated, making it easier to form a micellar gel structure. P188-3CPE (i.e., 2% LIM, 1% SDS and 0.5% bupivacaine (BUP)) had low viscosity at room temperature, facilitating administration, but rapidly gelled at body temperature. P188-3CPE enabled the flux of the antibiotic ciprofloxacin across the TM and completely eradicated otitis media from nontypable Haemophilus influenzae ( ) in chinchillas after a single administration.
Thermoresponsive polymers that undergo sol–gel transitions in the physiological temperature range have been widely used in biomedical applications. However, some commercially and clinically available thermoresponsive materials, particularly poloxamer 407 (P407), have the significant drawback of insufficient gel strength, which limit their performance. Furthermore, co-delivery with some small molecules, including chemical permeation enhancers (CPEs) can further impair the physical properties of P407. Here, we have developed a thermoresponsive platform by combination of CPEs with the poloxamer P188 to enable gelation at physiological temperatures and enhance gel strength. P188 gels at 60 °C, which is far above the physiological range. In combination with limonene (LIM) and sodium dodecyl sulfate (SDS), P188 gels at ∼25 °C, a temperature that in useful for biomedical applications. Gelation behavior was studied by small angle neutron scattering (SANS) experiments, which identified micelle-to-cubic mesophase transitions with increasing temperature. Analysis of the SANS intensities revealed that P188 micelles became larger as LIM or SDS molecules were incorporated, making it easier to form a micellar gel structure. P188-3CPE (i.e., 2% LIM, 1% SDS and 0.5% bupivacaine (BUP)) had low viscosity at room temperature, facilitating administration, but rapidly gelled at body temperature. P188-3CPE enabled the flux of the antibiotic ciprofloxacin across the TM and completely eradicated otitis media from nontypable Haemophilus influenzae ( NTHi ) in chinchillas after a single administration.
ArticleNumber e16923
Author Zhang, Zipei
Do, Changwoo
Kohane, Daniel S.
Li, Xiyu
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Keywords Chemical permeation enhancer
Otitis media
Thermoresponsive polymers
Tympanic membrane
Gelation
Language English
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2023 The Authors.
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Snippet Thermoresponsive polymers that undergo sol–gel transitions in the physiological temperature range have been widely used in biomedical applications. However,...
Thermoresponsive polymers that undergo sol-gel transitions in the physiological temperature range have been widely used in biomedical applications. However,...
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StartPage e16923
SubjectTerms Chemical permeation enhancer
Gelation
Otitis media
Thermoresponsive polymers
Tympanic membrane
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Title Enhancement of polymer thermoresponsiveness and drug delivery across biological barriers by addition of small molecules
URI https://dx.doi.org/10.1016/j.heliyon.2023.e16923
https://www.ncbi.nlm.nih.gov/pubmed/37484344
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