Characterizing Drug-Polymer Bead Interactions Using Isothermal Titration Calorimetry

Tanya Swaine, Pedro Garcia, Yiqing Tang, Andrew Lewis, Gareth Parkes, Laura Waters

Research output: Contribution to journalArticle

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Abstract

Isothermal titration calorimetry was used to investigate thermodynamic and kinetic binding interactions between 4 clinically relevant drugs: doxorubicin (Dox), irinotecan (Iri), mitoxantrone (Mitox), and topotecan (Topo) and a range of commercially available embolization microspheres. Five drug-eluting beads were chosen to consider the effect of bead size (ranging from 70-150 μm to 500-700 μm) and bead type (sulfonate-modified polyvinylalcohol hydrogel, known commercially as DC BeadM1™ and a sulfonate-modified polyethylene glycol hydrogel bead, known commercially as LifePearl™). The molar ratio of drug to SO 3 was found to be 0.9:1, 0.8:1, 0.4:1, and 0.9:1 for Dox, Iri, Mitox, and Topo, respectively. These findings indicate the steric effects of drug shape, charge, and size on binding ability. Four distinct bead sizes all produced drug:bead binding ratios of >0.9:1 doxorubicin:SO 3 , thus indicating that bead size does not affect binding stoichiometry. Interestingly, bead size did affect the rate of binding as bead size was found to be indirectly proportional to binding rate. Finally, it was found for the sulfonate-modified polyethylene glycol hydrogel beads that doxorubicin binding was faster (at certain ratios of drug to bead) than that for the sulfonate-modified polyvinylalcohol hydrogel yet was maximal at a drug to bead ratio of only 0.7:1.

Original languageEnglish
Pages (from-to)1772-1778
Number of pages7
JournalJournal of Pharmaceutical Sciences
Volume108
Issue number5
Early online date19 Dec 2018
DOIs
Publication statusPublished - 1 May 2019

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Calorimetry
Polymers
irinotecan
Hydrogel
Doxorubicin
Pharmaceutical Preparations
Topotecan
Mitoxantrone
Microspheres
Thermodynamics

Cite this

Swaine, Tanya ; Garcia, Pedro ; Tang, Yiqing ; Lewis, Andrew ; Parkes, Gareth ; Waters, Laura. / Characterizing Drug-Polymer Bead Interactions Using Isothermal Titration Calorimetry. In: Journal of Pharmaceutical Sciences. 2019 ; Vol. 108, No. 5. pp. 1772-1778.
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abstract = "Isothermal titration calorimetry was used to investigate thermodynamic and kinetic binding interactions between 4 clinically relevant drugs: doxorubicin (Dox), irinotecan (Iri), mitoxantrone (Mitox), and topotecan (Topo) and a range of commercially available embolization microspheres. Five drug-eluting beads were chosen to consider the effect of bead size (ranging from 70-150 μm to 500-700 μm) and bead type (sulfonate-modified polyvinylalcohol hydrogel, known commercially as DC BeadM1™ and a sulfonate-modified polyethylene glycol hydrogel bead, known commercially as LifePearl™). The molar ratio of drug to SO 3 − was found to be 0.9:1, 0.8:1, 0.4:1, and 0.9:1 for Dox, Iri, Mitox, and Topo, respectively. These findings indicate the steric effects of drug shape, charge, and size on binding ability. Four distinct bead sizes all produced drug:bead binding ratios of >0.9:1 doxorubicin:SO 3 −, thus indicating that bead size does not affect binding stoichiometry. Interestingly, bead size did affect the rate of binding as bead size was found to be indirectly proportional to binding rate. Finally, it was found for the sulfonate-modified polyethylene glycol hydrogel beads that doxorubicin binding was faster (at certain ratios of drug to bead) than that for the sulfonate-modified polyvinylalcohol hydrogel yet was maximal at a drug to bead ratio of only 0.7:1.",
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Characterizing Drug-Polymer Bead Interactions Using Isothermal Titration Calorimetry. / Swaine, Tanya; Garcia, Pedro; Tang, Yiqing; Lewis, Andrew; Parkes, Gareth; Waters, Laura.

In: Journal of Pharmaceutical Sciences, Vol. 108, No. 5, 01.05.2019, p. 1772-1778.

Research output: Contribution to journalArticle

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T1 - Characterizing Drug-Polymer Bead Interactions Using Isothermal Titration Calorimetry

AU - Swaine, Tanya

AU - Garcia, Pedro

AU - Tang, Yiqing

AU - Lewis, Andrew

AU - Parkes, Gareth

AU - Waters, Laura

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AB - Isothermal titration calorimetry was used to investigate thermodynamic and kinetic binding interactions between 4 clinically relevant drugs: doxorubicin (Dox), irinotecan (Iri), mitoxantrone (Mitox), and topotecan (Topo) and a range of commercially available embolization microspheres. Five drug-eluting beads were chosen to consider the effect of bead size (ranging from 70-150 μm to 500-700 μm) and bead type (sulfonate-modified polyvinylalcohol hydrogel, known commercially as DC BeadM1™ and a sulfonate-modified polyethylene glycol hydrogel bead, known commercially as LifePearl™). The molar ratio of drug to SO 3 − was found to be 0.9:1, 0.8:1, 0.4:1, and 0.9:1 for Dox, Iri, Mitox, and Topo, respectively. These findings indicate the steric effects of drug shape, charge, and size on binding ability. Four distinct bead sizes all produced drug:bead binding ratios of >0.9:1 doxorubicin:SO 3 −, thus indicating that bead size does not affect binding stoichiometry. Interestingly, bead size did affect the rate of binding as bead size was found to be indirectly proportional to binding rate. Finally, it was found for the sulfonate-modified polyethylene glycol hydrogel beads that doxorubicin binding was faster (at certain ratios of drug to bead) than that for the sulfonate-modified polyvinylalcohol hydrogel yet was maximal at a drug to bead ratio of only 0.7:1.

KW - Isothermal titration calorimetry

KW - Polymer

KW - Drug-eluting beads

KW - Binding

KW - Doxorubicin

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