Amino modified metal-organic frameworks as pH-responsive nanoplatforms for safe delivery of camptothecin

Abstract

and MIL-101(Fe) metal-organic frameworks (MOFs) are excellent vehicles for drug delivery systems (DDSs) due to their high biocompatibility and stability in physiological fluids, as well as their pore diameter in the mesoporous range.Although they are appropriate for the internal diffusion of 20-(S)-camptothecin (CPT), a strongly cytotoxic molecule with excellent antitumor activity, no stable delivery system has been proposed so far for this drug based in MOFs. We here present novel DDSs based in amine functionalized MIL-100(Fe) and MIL-101(Fe) nanoMOFs with covalently bonded CPT. These CPT nanoplatforms are able to incorporate almost 20% of this molecule and show high stability at physiological pH, with no non-specific release.Based on their surface charge, some of these CPT loaded nanoMOFs present improved cell internalization in in vitro experiments. Moreover, a strong response to acid pH is observed, with up to four fold drug discharge at pH 5, which boost intracellular release by endosomolytic activity. These novel DDSs will help to achieve safe delivery of the very cytotoxic CPT, allowing to reduce the therapeutic dose and minimizing drug secondary effects.

Anti-Influenza Virus Study of Composite Material with MIL-101(Fe)-Adsorbed Favipiravir

“…The drug was given at a dose of 9 wt% and was released completely after 2 weeks [ 39 ]. Ibuprofen loading and release studies of MIL-100 and MIL-101 found that MIL-101 can load 1.4 g of ibuprofen per gram, demonstrating a high drug loading rate and controlled release [ 40 ]. Cabrera-Garcia et al [ 41 ] synthesized amino-functionalized MIL-100(Fe)-loaded camptothecin.…”

Recent advances in nanosized metal organic frameworks for drug delivery and tumor therapy

“…1B shows that the release of DS gradually increases from 35% (pH 8.0) to 80% (pH 5.0) within 132 hours, thus indicating the ability of MIL-125 to release the drug at low pH. Moreover, other Fe-based nano-MOFs, such as MIL-53, 14,36 MIL-100-NH 2 37 and MIL-101 38 have been applied in pH responsive drug transport.…”

Estructuras metal-orgánicas (MOFs) nanoestructuradas para la liberación controlada de fármacos

“…Más aun, la funcionalidad de los grupos carboxílicos de sus ligandos orgánicos ha sido modificada con grupos amino, haciendo posible el acomodo de macromoléculas en sus cavidades, por interacciones de fisisorción. Estos grupos amino son susceptibles a reaccionar a cambios de pH, lo cual puede estimular la liberación del fármaco luego de atravesar la membrana celular y mejorar la liberación sostenible del fármaco (Cabrera-García et al, 2019).…”

“…Su baja toxicidad, fácil preparación de nanopartículas y relativa labilidad de los enlaces metal-ligando favorecen su biodegradabilidad. Además, son eficientes como agentes de contraste en imágenes de resonancia magnética, tomografía por computadora e imagenología óptica, como agentes sensores en terapia fototermal y fotodinámica, y como sistemas de liberación de fármacos (Cabrera-García et al, 2019). En un trabajo reciente (Unamuno et al, 2018), se efectúo la encapsulación de gentamicina en dos MOFs biocompatibles de carboxilatos de hierro y zirconio mediante una simple impregnación.…”