Supramolecular capsules based on Metal-Organic Framework for drug delivery

Author(s)

Marina Paiva Abuçafy

• Document type: Doctoral Thesis
• Press: Araraquara. 2020-10-22.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Ciências Farmacêuticas. Araraquara
• Defense date: 2020-09-24
• Advisor: Leila Aparecida Chiavacci Favorin; Regina Celia Galvão Frem

Abstract

Metal-Organic Frameworks are highly porous and crystalline coordination polymers made up of covalent interactions between metallic ions or clusters and organic ligands. Among some superstructures that can be developed based on MOFs, the capsules stand out, which has attracted a lot of interest from researchers because it is a material that, in addition to the porosity usually found in this type of material, can have cavities (hollow capsules) inside. The use of capsules based on MOFs as drug delivery systems has progressed, particularly to overcome the limitations of carriers already explored in the literature, providing the possibility of transporting large molecules or a high mass of the molecule of interest. Within this context, capsules based on MOFs HKUST, ZIF-8 and MIL-100 (Fe) were developed in this work by three different methods: using molds, pickering emulsion and spray drying, aiming to form a double loading system for the treatment of cancer. The materials were physically and chemically characterized and the capsules based on MIL-100 (Fe) developed by spray drying proved to be more promising for pharmaceutical application, presenting an average diameter of 800 nm. The capsules exhibited greater encapsulation efficiency for the drug methotrexate (MTX) when compared to its occlusion in nanoparticles of the same material, which corroborates with its properties and the presence of hollow cavities observed by electron microscopy, besides the increase of the system size. In addition, the capsules also showed a high capacity to encapsulate large molecules, such as the collagenase enzyme (91.7%). The enzyme activity test showed that the collagenase remained with its activity preserved even after the process of encapsulation by spray drying. As for the release processes of the porous matrix, the MTX drug release profile showed that the capsules have a greater capacity to prolong the release of methotrexate, so that after 48 hours, only 50% of the drug was released, while almost 93% of the drug was released. drug present in the MOF MIL-100 nanoparticles had already been released, which can also be justified by the larger surface area of the nanoparticle. In addition, the capsule also controls the release of collagenase, allowing the use of this system as a material capable of transporting and releasing the drug and enzyme in combination. The evaluation of cytotoxicity in HaCat and A-375 cells revealed high cell viability of MIL-100 (Fe) capsules and, after 24 hours of incubation, capsules containing MTX and collagenase caused an increase in cytotoxicity, mainly in the cancer cell line, which confirms the antitumor action of the system composed of the drug and the protein. (AU)

• FAPESP's process: 16/11563-4 - Supramolecular capsules based on metal-organic framework applied for drug release
• Grantee: Marina Paiva Abuçafy
• Support Opportunities: Scholarships in Brazil - Doctorate