Enhanced Drug Delivery by Dissolution of Amorphous Drug Encapsulated in a Water Unstable Metal–Organic Framework (MOF)

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.MOF‐Transporter: Eine Wirkstofftransportstrategie, bei der ein Metall‐organisches Gerüst die Kristallisation der amorphen Phase hemmt und dann unter hydrolytischer Zersetzung den Wirkstoff freisetzt, stellt einen neuartigen Ansatz für die Verabreichung schwerlöslicher Verbindungen dar und überwindet zugleich den traditionellen Schwachpunkt amorpher Wirkstoffe: die physikalische Instabilität der amorphen Form.