Polymer conjugated retinoids for controlled transdermal delivery
Name
nihms909867.pdf
Description
Accepted version
Size
950.45 KB
Format
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Checksum (MD5)
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Author(s)
Castleberry, Steven A
Quadir, Mohiuddin Abdul
Sharkh, Malak Abu
Shopsowitz, Kevin
Hammond, Paula T
Date Issued
July 2017
Journal
Journal of Controlled Release
Publisher
Elsevier
Citation
Castleberry, Steven A. "Polymer conjugated retinoids for controlled transdermal delivery." Journal of Controlled Release 262 (September 28, 2017): 1-9 © 2017 Publisher
Version
Author's final manuscript
Abstract
All-trans retinoic acid (ATRA), a derivative of vitamin A, is a common component in cosmetics and commercial acne creams as well as being a first-line chemotherapeutic agent. Today, formulations for the topical application of ATRA rely on creams and emulsions to incorporate the highly hydrophobic ATRA drug. These strategies, when applied to the skin, deliver ATRA as a single bolus, which is immediately taken up into the skin and contributes to many of the known adverse side effects of ATRA treatment, including skin irritation and hair loss. Herein we present a new concept in topical delivery of retinoids by covalently bonding the drug through a hydrolytically degradable ester linkage to a common hydrophilic polymer, polyvinyl alcohol (PVA), creating an amphiphilic nanomaterial that is water-soluble. This PVA bound ATRA can then act as a pro-drug and accumulate within the skin to allow for the sustained controlled delivery of active ATRA. This approach was demonstrated to release active ATRA out to 10 days in vitro while significantly enhancing dermal accumulation of the ATRA in explant pig skin. In vivo we demonstrate that the pro-drug formulation reduces application site inflammation compared to free ATRA and retains the drug at the application site at measurable quantities for up to six days. Keywords: all-trans retinoic acid; poly (vinyl alcohol); polymer conjugate; transdermal drug delivery
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.jconrel.2017.07.003
