From burst to controlled release: using hydrogel crosslinking chemistry to tune release of micro-crystalline active pharmaceutical ingredients
Name
d4pm00186a.pdf
Description
Published version
Size
1.06 MB
Format
Adobe PDF
Checksum (MD5)
c82ead8bf5eea7aec51758ea5d0a0fe1
Author(s)
Manghnani, Purnima N
Nelson, Arif Z
Wong, Kelvin
Lee, Yi Wei
Khan, Saif A
Doyle, Patrick S
Date Issued
January 21, 2025
Journal
RSC Pharmaceutics
Publisher
Royal Society of Chemistry
Citation
Manghnani, Purnima N, Nelson, Arif Z, Wong, Kelvin, Lee, Yi Wei, Khan, Saif A et al. 2025. "From burst to controlled release: using hydrogel crosslinking chemistry to tune release of micro-crystalline active pharmaceutical ingredients." RSC Pharmaceutics, 2 (1).
Version
Final published version
Abstract
Hydrogels have been widely studied as substrates for drug delivery and tissue engineering owing to their biocompatibility and ability to swell in aqueous media. Encapsulation of lipophilic active pharmaceutical ingredients (API) as crystalline micro-/nanoparticles within hydrogel formulations has shown promise for improving their bioavailability and achieving high drug load. Despite the size reduction of the API within the hydrogel mesh, the bioavailability of these formulations is largely governed by the inherent ability of the hydrogel polymer backbone to release the API. In this work, Michael addition-based Polyethylene glycol (PEG) hydrogels are developed for micro-crystalline fenofibrate (Fen) encapsulation. Using a parallelized step emulsification device, API nanoemulsion (NE) loaded micro-hydrogels are fabricated and subsequently subjected to anti-solvent extraction for API crystallization. The bi-molecular nature of the Michael addition reaction provides modular incorporation of crosslinking functional groups leading to precise temporal control over hydrogel degradation, thereby offering a sensitive handle on the release of micro-crystalline fenofibrate. By merely changing the chemical identity of the hydrogel cross-link, complete Fen release could be tuned from 4 hours to 10 days. Furthermore, the interaction of crystallizing Fen and PEG within the micro-hydrogel environment led to eutectic formation. This unique feature offered a second handle on the Fen release from the composite micro-hydrogels.
MIT Department
Singapore-MIT Alliance in Research and Technology (SMART)
Massachusetts Institute of Technology. Department of Chemical Engineering
Terms of Use
Creative Commons Attribution-Noncommercial
Persistent DSpace Link
DOI of Published Version
10.1039/d4pm00186a
