Acid-Resistant Mesoporous Metal–Organic Framework toward Oral Insulin Delivery: Protein Encapsulation, Protection, and Release

Abstract

Diabetes affects millions of people worldwide and the number of diagnoses continues to climb annually. Though several effective medications and therapeutic methods have been developed to treat type 1 (T1DM) and type 2 (T2DM) diabetes mellitus, direct insulin injection remains the only effective treatment for insulin resistant (IR) diabetes patients. Here, we immobilize insulin in a crystalline mesoporous metal-organic framework (MOF), NU-1000, and obtain a high loading of ∼40 wt % in only 30 min. The acid-stable MOF capsules are found to effectively prevent insulin from degrading in the presence of stomach acid and the digestive enzyme, pepsin. Furthermore, the encapsulated insulin can be released from NU-1000 under simulated physiological conditions.

Stabilization of Formate Dehydrogenase in a Metal–Organic Framework for Bioelectrocatalytic Reduction of CO2

“…Metal–organic frameworks (MOFs), a class of tunable materials comprised of organic linkers and inorganic nodes, have been used as porous supports to enhance the stability and, in some cases, catalytic activity of the encapsulated enzymes . In particular, zirconium‐based MOFs (the NU‐10xx series) demonstrate excellent stability at a wide range of acidic and basic pH . The hierarchical pore structure allows for the inclusion of large catalytic guest molecules, while allowing substrate diffusion through an auxiliary channel and access to the catalyst through apertures connecting the channels (Scheme a).…”

Nanoarchitectonics of Biofunctionalized Metal–Organic Frameworks with Biological Macromolecules and Living Cells

“…The study found that the proper tailoring of pore size and surface charge was critical for ensuring favorable interactions with protein (e.g., insulin) which in turn, will determine the loading amount of protein. The 1D pores of NU‐1000 allowed insulin molecule to diffuse through the framework but pepsin was excluded while being transported by the bloodstream due to the size mismatch ( Figure ) …”

“…Insulin remains folded while insulin@NU‐1000 can withstand exposure to stomach acid/digestive enzyme, with the release of pepsin and insulin occurring in the PBS solution (bloodstream). Reproduced with permission . Copyright 2018, American Chemical Society.…”

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

“…[10,11] Fore xample,M OFs have been demonstrated to be excellent candidates for micro/ nanomedicine-extended or controlled cargo delivery. [12][13][14][15][16] In these delivery models,M OFs with long-term chemical stability in media serve as drug release regulators upon activation by diverse stimuli such as media pH, temperature or pressure. [10] MOFs using as low drug release model are beneficial for moderate to high solubility compounds and may improve chemical stability [12][13][14][15] of molecules by limiting total exposure of the compound in the digestive tract.…”