Autores
Garzón Serrano, A.Y. (UNIVERSIDAD NACIONAL DE COLOMBIA, SEDE BOGOTÁ) ; Sierra Avila, C.A. (UNIVERSIDAD NACIONAL DE COLOMBIA, SEDE BOGOTÁ) ; Pérez Umaña, Y.A. (UNIVERSIDAD NACIONAL DE COLOMBIA, SEDE BOGOTÁ)
Resumo
In the last years, biological metal-organic frameworks (bioMOFs) have been
studied as controlled drug delivery systems, thanks to their organism
biocompatibility. Here, the study of controlled delivery of a new bioMOF based
on protocatechuic acid (PCA), and their preliminary evaluation as a drug
carrier, using cannabidiol (CBD) as a drug model, is presented. The PCA and CBD
release profiles were studied in water and phosphate buffer solution (pH 4.0 and
7.2). The results show controlled delivery of PCA and differences in quantity
release depending on the pH environment. In the drug model, similar behavior and
a low percentage of CBD release were observed. This preliminary study encourages
deeply the optimization of conditions to achieve a higher drug loaded in the new
bioMOF studied
Palavras chaves
Phenolic acids; bioMOFs; controlled delivery
Introdução
Inside porous materials, metal-organic frameworks (MOFs) outstands a great
potential as drug delivery systems due to their pore size and high surface area,
which allows a load of drug with therapeutic purposes. In addition, their
sustained delivery profile, and higher yield of storage, have carried an
increment in medical applications, where MOFs could be used in the treatment of
cancer, allowing efficient drug administration in the human body (MALLAKPOUR, S.
et al., 2022). Considering the low or null toxicity that must be characteristic
of the drug carrier systems, biomolecules have been increment used as organic
linkers, a new MOFs subfamily known as bioMOFs. Recently, a new structure based
on vitamin C and zinc (bioNICS-1) demonstrated structural stability as well as
controlled delivery of bioactive compounds (TAJNŠEK, T. K. et al., 2022). This
highlights the importance of studying the degradation of new bioMOFs upon
contact with different media, especially physiological ones. On the other hand,
the majority of bioMOFs reported employs amino acids, peptides, proteins, and
cyclodextrin as biomolecules, being few studies based on phenolic acid as
organic linkers. In this case, gallic acid (GA) has been the protagonist in the
development of new structures, along with magnesium (COOPER, L. et al., 2015),
calcium (HIDALGO, et al., 2017), and copper (SHARMA, S., et al., 2019). Owing to
the results obtained with bioMOF based on GA and magnesium, as well as their
possibility of drug carrier, Sharma et al. proved the therapeutic potential of
this bioMOF as cannabidiol (CBD) carrier and their effect in glioblastoma, where
the reduction of reactive oxygen species was achieved due to sustained
codelivery of GA and CBD (SHARMA, A., et al., 2021). Considering the importance
of this field, our research shows the profile release obtained in a new bioMOF
based on protocatechuic acid (PCA), and their preliminary evaluation as a drug
carrier, using CBD as a drug model. The results show a controlled and sustained
PCA and CBD delivery, demonstrating the possible use of this new bioMOF as a
drug delivery system.
Material e métodos
BioMOF based on PCA (bioUNAL-1) was synthesized by dissolving 308 g (2 mols) of
PCA in a vial with 4 mL of water. A 10 M aqueous solution of KOH was added
dropwise until the pH reached 9. In a second vial was dissolved 120 g (1 mol) of
magnesium sulfate with 2 mL of water, and it was added to the first solution. The
reaction mixture was placed in an ultrasonic bath for 60 minutes. The white solid
was recovered by 2 cycles of washing (50/50 - distilled water/ethanol) and
centrifugation (2500 rpm, 6 minutes). Finally, the white solid was taken up with
ethanol and dried at room temperature (yield 85%). For the release of PCA from
bioUNAL-1, it was studied in water and phosphate buffer solution (PBS) of pH 4.0
and 7.2. 10 mg of bioUNAL-1 was dispersed in 10 mL of each medium and incubated at
37 °C in a sealed vial for 2 days. 1 mL aliquots were taken at various time points
and filtered using a 0.2 μm filter before PCA measurement (289 nm in UV-Vis
spectrometer). The CBD-loaded was realized as Sharman et al reported (SHARMA, A.,
et al., 2021), and the amount of CBD release was followed by HPLC analysis.
Resultado e discussão
The release profile obtained shows that bioUNAL-1 acted as a source of PCA
delivery in a sustained way even for 48 hours, and for the three mediums evaluated
(Figure 1A). The two first hours evidenced a burst effect, which could be
attributed to bioUNAL-1 instability in aqueous mediums, and to competition between
the organic linker and phosphate ions for the metal center coordination.
Interestingly, the PCA release stays below 50% for low pH, being attractive for
cancer treatment where a controlled release of the drug in an acidic environment
is desired (CAI, W., et al. 2021). In the case of CBD release (Figure 1B),
similar behavior to PCA, and low release (6%) during 8 hours is observed,
suggesting a drug sustained delivery in an acid environment. Nevertheless, the
drug-loaded conditions and the kinetic study require more deep study to improve
and understand the bioUNAL-1 behavior as a CBD carrier.
(A) PCA release and (B) CBD release profile from bioUNAL-1 in water (black), PBS at pH 7.2 (red), and pH 4.0 (blue).
Conclusões
The evaluation in aqueous and PBS (pH 7.2 and 4.0) mediums shows a PCA sustained
release profile between 7 and 48 hours of the new bioUNAL-1 material.
Additionally, a controlled release of 50% in 48 hours is observed for acid
environments, which is highly desirable for controlled and sustained release
systems in cancer treatments. Finally, in its preliminary evaluation, as a CBD
carrier, a possible sustained release in acidic pH is observed, which encourages
further study of the encapsulation and release time, considering the positive
effects of co-release reported for bioMOFs as drug delivery systems.
Agradecimentos
We acknowledge the Vicerrectoria de Investigación sede Bogotá, Facultad de
Ciencias, and Departamento de Química of Universidad Nacional de Colombia for
financial support.
Referências
MALLAKPOUR, S. et al. Application of MOF Materials as Drug Delivery Systems for Cancer Therapy and Dermal Treatment. Coord. Chem. Rev. 2022, 451, 214262. https://doi.org/10.1016/j.ccr.2021.214262.
TAJNŠEK, T. K. et al. Design and Degradation of Permanently Porous Vitamin C and Zinc-Based Metal-Organic Framework. Commun. Chem. 2022, 5 (1). https://doi.org/10.1038/s42004-022-00639-x.
COOPER, L. et al. A Biocompatible Porous Mg-Gallate Metal–Organic Framework as an Antioxidant Carrier. Chem. Commun. 2015, No. 27. https://doi.org/10.1039/C5CC00745C.
HIDALGO, T. et al. Crystal Structure Dependent in Vitro Antioxidant Activity of Biocompatible Calcium Gallate MOFs †. J. Mater. Chem. B 2017, 5 (15), 2813–2822. https://doi.org/10.1039/c6tb03101c.
SHARMA, S. et al. Copper-Gallic Acid Nanoscale Metal-Organic Framework for Combined Drug Delivery and Photodynamic Therapy. ACS Appl. Bio Mater. 2019, 2 (5), 2092–2101. https://doi.org/10.1021/acsabm.9b00116.
SHARMA, A. et al. A Cannabidiol-Loaded Mg-Gallate Metal–Organic Framework-Based Potential Therapeutic for Glioblastomas. J. Mater. Chem. B 2021, 9, 2505–2514. https://doi.org/10.1039/D0TB02780D.
CAI, W. et al. Metal–Organic Framework-Based Stimuli-Responsive Systems for Drug Delivery. Adv. Sci. 2019, 6 (1). https://doi.org/10.1002/advs.201801526.
