Metal-Organic Frameworks for Drug Delivery Applications
In this work, a new type of particles denoted as MOFs or Metal-Organic Frameworks, have been studied as a new drug carriers. First, they were synthesised at the nanoscale (NPs) using, when possible, biofriendly methods. Their cytotoxicity, as well as that from their constitutive linkers, was evalua...
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| Format: | info:eu-repo/semantics/doctoralThesis |
| Language: | eng |
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2016
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| Online Access: | https://hdl.handle.net/10171/40927 |
| _version_ | 1793400501656616960 |
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| author | Tamames-Tabar, C. (Cristina) Horcajada, P. (Patricia) Blanco-Prieto, M.J. (María José) |
| author_facet | Tamames-Tabar, C. (Cristina) Horcajada, P. (Patricia) Blanco-Prieto, M.J. (María José) |
| author_sort | Tamames-Tabar, C. (Cristina) |
| collection | DSpace |
| description | In this work, a new type of particles denoted as MOFs or Metal-Organic Frameworks, have been studied as a new drug carriers.
First, they were synthesised at the nanoscale (NPs) using, when possible, biofriendly methods. Their cytotoxicity, as well as that from their constitutive linkers, was evaluated by the MTT test in murine macrophage (J774) and in cervix carcinoma (HeLa) cell lines, observing: (i) a low cytotoxicity of MOFs, comparable with other described particulated systems, (ii) a strong influence of the composition (toxicity order: Fe<Zr<Zn; hydrophilic<hydrophobic linkers), (iii) a higher cytotoxicity in J774 than HeLa, due to their higher phagocytosis activity and (iv) MIL-100(Fe)_NPs was an excellent candidate for bioapplications (IC50=0.7 mg¿mL-1). MIL-100(Fe)_NPs are rapidly cell-uptaken, being immediately internalised in J774 cells.
Next, the non-toxic bioflavonoid genistein (GEN) with antitumoral properties was successfully encapsulated in porous Fe or Zr carboxylate MOFs, achieving GEN payloads (160-340 g GEN¿mg formulation-1), higher than other existing formulations and dependent on their composition and topology. Furthermore, GEN was progressively released under simulated physiological conditions from 2 days to several weeks, being appropriate as long release drug delivery systems (DDS). Finally, the pharmacokinetics and bioavailability evaluation of MIL-100(Fe)_NPs¿ formulation was carried out in comparison with the free drug after its oral unique administration (30 mg¿Kg-1) to mice, depicting (i) higher and longer plasmatic levels, (ii) an increase in the relative and (iii) a better oral bioavailability and a mean residence time. Furthermore, higher and more prolonged drug levels were detected in organs, suggesting that the MOF worked as a drug shelter, protecting GEN from metabolisation.
Finally, a new biologically active MOF (denoted BioMIL-5), based on the antibacterial and dermatologically active azelaic acid (AzA) and Zn, was successfully synthesised by a totally biofriendly route. Both active components BioMIL-5 were slowly released to the media, either pure water or bacteria medium, upon its structural degradation. Its antibacterial activity was evidenced in S. aureus and in S. epidermidis, observing an interesting additive effect with however high minimal inhibitory (MIC) and minimal bactericidal concentrations (MBC), in agreement with the isolated components. Finally, BioMIL-5 exhibited a lengthened bactericidal (4.3 mg¿mL-1) and bacteriostatic (0.9 and 1.7 mg¿mL-1) in contact with S. epidermidis for one week. |
| format | info:eu-repo/semantics/doctoralThesis |
| id | oai:dadun.unav.edu:10171-40927 |
| institution | Universidad de Navarra |
| language | eng |
| publishDate | 2016 |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-409272020-03-23T17:31:40Z Metal-Organic Frameworks for Drug Delivery Applications Tamames-Tabar, C. (Cristina) Horcajada, P. (Patricia) Blanco-Prieto, M.J. (María José) Materias Investigacion::Ciencias de la vida Preparación de fármacos Análisis de fármacos Composición de fármacos Evaluación de fármacos In this work, a new type of particles denoted as MOFs or Metal-Organic Frameworks, have been studied as a new drug carriers. First, they were synthesised at the nanoscale (NPs) using, when possible, biofriendly methods. Their cytotoxicity, as well as that from their constitutive linkers, was evaluated by the MTT test in murine macrophage (J774) and in cervix carcinoma (HeLa) cell lines, observing: (i) a low cytotoxicity of MOFs, comparable with other described particulated systems, (ii) a strong influence of the composition (toxicity order: Fe<Zr<Zn; hydrophilic<hydrophobic linkers), (iii) a higher cytotoxicity in J774 than HeLa, due to their higher phagocytosis activity and (iv) MIL-100(Fe)_NPs was an excellent candidate for bioapplications (IC50=0.7 mg¿mL-1). MIL-100(Fe)_NPs are rapidly cell-uptaken, being immediately internalised in J774 cells. Next, the non-toxic bioflavonoid genistein (GEN) with antitumoral properties was successfully encapsulated in porous Fe or Zr carboxylate MOFs, achieving GEN payloads (160-340 g GEN¿mg formulation-1), higher than other existing formulations and dependent on their composition and topology. Furthermore, GEN was progressively released under simulated physiological conditions from 2 days to several weeks, being appropriate as long release drug delivery systems (DDS). Finally, the pharmacokinetics and bioavailability evaluation of MIL-100(Fe)_NPs¿ formulation was carried out in comparison with the free drug after its oral unique administration (30 mg¿Kg-1) to mice, depicting (i) higher and longer plasmatic levels, (ii) an increase in the relative and (iii) a better oral bioavailability and a mean residence time. Furthermore, higher and more prolonged drug levels were detected in organs, suggesting that the MOF worked as a drug shelter, protecting GEN from metabolisation. Finally, a new biologically active MOF (denoted BioMIL-5), based on the antibacterial and dermatologically active azelaic acid (AzA) and Zn, was successfully synthesised by a totally biofriendly route. Both active components BioMIL-5 were slowly released to the media, either pure water or bacteria medium, upon its structural degradation. Its antibacterial activity was evidenced in S. aureus and in S. epidermidis, observing an interesting additive effect with however high minimal inhibitory (MIC) and minimal bactericidal concentrations (MBC), in agreement with the isolated components. Finally, BioMIL-5 exhibited a lengthened bactericidal (4.3 mg¿mL-1) and bacteriostatic (0.9 and 1.7 mg¿mL-1) in contact with S. epidermidis for one week. 2016-05-18T12:43:54Z 2016-05-18T12:43:54Z 2014 2014-07-25 info:eu-repo/semantics/doctoralThesis https://hdl.handle.net/10171/40927 eng info:eu-repo/semantics/openAccess application/pdf |
| spellingShingle | Materias Investigacion::Ciencias de la vida Preparación de fármacos Análisis de fármacos Composición de fármacos Evaluación de fármacos Tamames-Tabar, C. (Cristina) Horcajada, P. (Patricia) Blanco-Prieto, M.J. (María José) Metal-Organic Frameworks for Drug Delivery Applications |
| title | Metal-Organic Frameworks for Drug Delivery Applications |
| title_full | Metal-Organic Frameworks for Drug Delivery Applications |
| title_fullStr | Metal-Organic Frameworks for Drug Delivery Applications |
| title_full_unstemmed | Metal-Organic Frameworks for Drug Delivery Applications |
| title_short | Metal-Organic Frameworks for Drug Delivery Applications |
| title_sort | metal-organic frameworks for drug delivery applications |
| topic | Materias Investigacion::Ciencias de la vida Preparación de fármacos Análisis de fármacos Composición de fármacos Evaluación de fármacos |
| url | https://hdl.handle.net/10171/40927 |
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