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Pulsatile Chemotherapeutic Delivery Profiles Using Magnetically Responsive Hydrogels

[Image: see text] Pulsatile chemotherapeutic delivery profiles may provide a number advantages by maximizing the anticancer toxicity of chemotherapeutics, reducing off-target side effects, and combating adaptive resistance. While these temporally dynamic deliveries have shown some promise, they have...

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Autores principales: Emi, Tania T., Barnes, Tanner, Orton, Emma, Reisch, Anne, Tolouei, Anita E., Madani, S. Zahra M., Kennedy, Stephen M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2018
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039960/
https://www.ncbi.nlm.nih.gov/pubmed/30019005
http://dx.doi.org/10.1021/acsbiomaterials.8b00348
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author Emi, Tania T.
Barnes, Tanner
Orton, Emma
Reisch, Anne
Tolouei, Anita E.
Madani, S. Zahra M.
Kennedy, Stephen M.
author_facet Emi, Tania T.
Barnes, Tanner
Orton, Emma
Reisch, Anne
Tolouei, Anita E.
Madani, S. Zahra M.
Kennedy, Stephen M.
author_sort Emi, Tania T.
collection PubMed
description [Image: see text] Pulsatile chemotherapeutic delivery profiles may provide a number advantages by maximizing the anticancer toxicity of chemotherapeutics, reducing off-target side effects, and combating adaptive resistance. While these temporally dynamic deliveries have shown some promise, they have yet to be clinically deployed from implantable hydrogels, whose localized deliveries could further enhance therapeutic outcomes. Here, several pulsatile chemotherapeutic delivery profiles were tested on melanoma cell survival in vitro and compared to constant (flatline) delivery profiles of the same integrated dose. Results indicated that pulsatile delivery profiles were more efficient at killing melanoma cells than flatline deliveries. Furthermore, results suggested that parameters like the duration of drug “on” periods (pulse width), delivery rates during those periods (pulse heights), and the number/frequency of pulses could be used to optimize delivery profiles. Optimization of pulsatile profiles at tumor sites in vivo would require hydrogel materials capable of producing a wide variety of pulsatile profiles (e.g., of different pulse heights, pulse widths, and pulse numbers). This work goes on to demonstrate that magnetically responsive, biphasic ferrogels are capable of producing pulsatile mitoxantrone delivery profiles similar to those tested in vitro. Pulse parameters such as the timing and rate of delivery during “on” periods could be remotely regulated through the use of simple, hand-held magnets. The timing of pulses was controlled simply by deciding when and for how long to magnetically stimulate. The rate of release during pulse “on” periods was a function of the magnetic stimulation frequency. These findings add to the growing evidence that pulsatile chemotherapeutic delivery profiles may be therapeutically beneficial and suggest that magnetically responsive hydrogels could provide useful tools for optimizing and clinically deploying pulsatile chemotherapeutic delivery profiles.
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spelling pubmed-60399602018-07-15 Pulsatile Chemotherapeutic Delivery Profiles Using Magnetically Responsive Hydrogels Emi, Tania T. Barnes, Tanner Orton, Emma Reisch, Anne Tolouei, Anita E. Madani, S. Zahra M. Kennedy, Stephen M. ACS Biomater Sci Eng [Image: see text] Pulsatile chemotherapeutic delivery profiles may provide a number advantages by maximizing the anticancer toxicity of chemotherapeutics, reducing off-target side effects, and combating adaptive resistance. While these temporally dynamic deliveries have shown some promise, they have yet to be clinically deployed from implantable hydrogels, whose localized deliveries could further enhance therapeutic outcomes. Here, several pulsatile chemotherapeutic delivery profiles were tested on melanoma cell survival in vitro and compared to constant (flatline) delivery profiles of the same integrated dose. Results indicated that pulsatile delivery profiles were more efficient at killing melanoma cells than flatline deliveries. Furthermore, results suggested that parameters like the duration of drug “on” periods (pulse width), delivery rates during those periods (pulse heights), and the number/frequency of pulses could be used to optimize delivery profiles. Optimization of pulsatile profiles at tumor sites in vivo would require hydrogel materials capable of producing a wide variety of pulsatile profiles (e.g., of different pulse heights, pulse widths, and pulse numbers). This work goes on to demonstrate that magnetically responsive, biphasic ferrogels are capable of producing pulsatile mitoxantrone delivery profiles similar to those tested in vitro. Pulse parameters such as the timing and rate of delivery during “on” periods could be remotely regulated through the use of simple, hand-held magnets. The timing of pulses was controlled simply by deciding when and for how long to magnetically stimulate. The rate of release during pulse “on” periods was a function of the magnetic stimulation frequency. These findings add to the growing evidence that pulsatile chemotherapeutic delivery profiles may be therapeutically beneficial and suggest that magnetically responsive hydrogels could provide useful tools for optimizing and clinically deploying pulsatile chemotherapeutic delivery profiles. American Chemical Society 2018-05-15 2018-07-09 /pmc/articles/PMC6039960/ /pubmed/30019005 http://dx.doi.org/10.1021/acsbiomaterials.8b00348 Text en Copyright © 2018 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Emi, Tania T.
Barnes, Tanner
Orton, Emma
Reisch, Anne
Tolouei, Anita E.
Madani, S. Zahra M.
Kennedy, Stephen M.
Pulsatile Chemotherapeutic Delivery Profiles Using Magnetically Responsive Hydrogels
title Pulsatile Chemotherapeutic Delivery Profiles Using Magnetically Responsive Hydrogels
title_full Pulsatile Chemotherapeutic Delivery Profiles Using Magnetically Responsive Hydrogels
title_fullStr Pulsatile Chemotherapeutic Delivery Profiles Using Magnetically Responsive Hydrogels
title_full_unstemmed Pulsatile Chemotherapeutic Delivery Profiles Using Magnetically Responsive Hydrogels
title_short Pulsatile Chemotherapeutic Delivery Profiles Using Magnetically Responsive Hydrogels
title_sort pulsatile chemotherapeutic delivery profiles using magnetically responsive hydrogels
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039960/
https://www.ncbi.nlm.nih.gov/pubmed/30019005
http://dx.doi.org/10.1021/acsbiomaterials.8b00348
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