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Enhanced Drug Delivery by Dissolution of Amorphous Drug Encapsulated in a Water Unstable Metal–Organic Framework (MOF)
Author(s) -
Suresh Kuthuru,
Matzger Adam J.
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201907652
Subject(s) - dissolution , amorphous solid , solubility , drug delivery , chemical engineering , supersaturation , chemistry , crystallization , drug , materials science , nanotechnology , organic chemistry , pharmacology , medicine , engineering
Abstract Encapsulating a drug molecule into a water‐reactive metal–organic framework (MOF) leads to amorphous drug confined within the nanoscale pores. Rapid release of drug occurs upon hydrolytic decomposition of MOF in dissolution media. Application to improve dissolution and solubility for the hydrophobic small drug molecules curcumin, sulindac, and triamterene is demonstrated. The drug@MOF composites exhibit significantly enhanced dissolution and achieves high supersaturation in simulated gastric and/or phosphate buffer saline media. This combination strategy where MOF inhibits crystallization of the amorphous phase and then releases drug upon MOF irreversible structural collapse represents a novel and generalizable approach for drug delivery of poorly soluble compounds while overcoming the traditional weakness of amorphous drug delivery: physical instability of the amorphous form.