Design, preparation and characterization of pH-responsive prodrug micelles with hydrolyzable anhydride linkages for controlled drug delivery
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Date
2017-01
Journal Title
Journal ISSN
Volume Title
Publisher
Journal of Colloid and Interface Science
Abstract
We report a new prodrug micelle-based approach in which a model hydrophobic non-steroidal antiinflammatory
drug (NSAID), ibuprofen (Ibu), is tethered to amphiphilic methoxy polyethylene glycolpolypropylene
fumarate (mPEG-PPF) diblock copolymer via hydrolytic anhydride linkages for potential
controlled release applications of NSAIDs. Synthesized mPEG-PPF-Ibu polymer drug conjugates (PDCs)
demonstrated high drug conjugation efficiency ( 90%) and self-assembled to form micellar nanostructures
in aqueous medium with critical micelle concentrations ranging between 16 and 30 lg/mL. The
entrapment efficiency of Ibu in prepared PDC micelles was as high as 18% (w/w). Crosslinking of prodrug
micelles with N,N0-dimethylaminoethyl methacrylate conferred pH-responsive characteristics.
pH-responsive PDC micelles averaged 100 nm in size at pH 7.4 and exhibited concomitant changes in size
upon incubation in physiologically relevant mildly acidic conditions. Ibu release was observed to increase
with increasing acidic conditions and could be controlled by varying the amount of crosslinker used.
Furthermore, the prepared mPEG-PPF-based micelles demonstrated excellent cytocompatibility and cellular
internalization in vitro. More importantly, PDC micelles exerted anti-inflammatory effects by significantly
decreasing monosodium urate crystal-induced prostaglandin E2 levels in rabbit synoviocyte
cultures in vitro. Cumulatively, our results indicate that this new prodrug micelle approach is promising
for NSAID-based therapies in the treatment of arthritis and cancer.
Description
Keywords
pH responsive Prodrug micelles Crosslinkable Anhydride linkages Polypropylene fumarate Controlled release
Citation
Girija S, Adarsh R, Vineeth MV, Jayabalan M, Shivaram S. Design, preparation and characterization of pH-responsive prodrug micelles with hydrolyzable anhydride linkages for controlled drug delivery. Journal of Colloid and Interface Science. 2017