Encapsulação do flavonoide crisina: uma revisão sobre as metodologias utilizadas e potencial biológico

Filho, Carlos Borges; Gomes, Marcelo Gomes de; Kemmerich, Magali; Deus, Cassandra de; Menezes, Cristiano Ragagnin de

RESUMO:

O flavonoide crisina tem sido apresentado como tendo numerosos e promissores efeitos bioativos, como antioxidante, anticonvulsivante, anti-hipertensivo, anti-inflamatório, antineoplásico, anti-hiperlipidêmico e antidepressivo. No entanto, um dos principais desafios para o avanço dos estudos sobre a bioatividade da crisina é sua baixa biodisponibilidade em humanos. Assim, visando superar essa barreira, diversos estudos têm demonstrado o potencial bioativo de cápsulas contendo crisina. O objetivo desta revisão é apresentar as principais metodologias utilizadas para o encapsulamento da crisina e seus principais efeitos biológicos demonstrados até o momento. Nossa intenção é oferecer caminhos para o avanço das pesquisas na área de encapsulação de flavonoides. Quanto às técnicas de encapsulamento, verificou-se que são diversas, e os agentes encapsulantes mais recorrentes são os polímeros PEG, PLGA e seus derivados, além de outros agentes como PCL, albumina, lipídeos e quitosana. Os efeitos bioativos das cápsulas também são numerosos, sendo os efeitos anticarcinogênicos os mais frequentes, além de outros efeitos como antioxidante, antidiabético, antimicrobiano e neuroprotetor. Em conclusão, verificamos a falta de utilização de técnicas verdes para o encapsulamento de crisina, e a produção de emulsões lipídeo-água e dissolução da crisina em etanol parecem ser alternativas neste aspecto. Além disso, o potencial bioativo destas cápsulas pode ainda ser avaliado em outros modelos experimentais, e deve-se avançar para ensaios clínicos e aplicação em formulações alimentícias.

Palavras-chave:
anticarcinogênico; nanocápsulas; biodisponibilidade; PEG-PLGA

[1] E-mail: cristiano.ufsm@gmail.com. ^*Corresponding author.

Summarized Methodology	Biological Potential	Reference
Dissolution in PCL-PEG-PCL in DCM + dH₂O + Sonication + Solvent evaporation	Anticancer in breast cancer cell line	EATEMADI et al. (2016EATEMADI, A. et al. Synthesis and Characterization of chrysin-loaded PCL-PEG-PCL nanoparticle and its effect on breast cancer cell line. Biomedicine & Pharmacotherapy, v.84, p.1915-1922, 2016. Available from: <Available from: https://doi.org/10.1016/j.biopha.2016.10.095 >. Accessed: Dec. 08, 2022. doi: 10.1016/j.biopha.2016.10.095. https://doi.org/10.1016/j.biopha.2016.10... )
Mix of water-surfactant solution containing chrysin and stearic acid completely melted + Equilibrate at ~75 °C + Homogenization + Agitation near ice cold water + Centrifugation + Resuspension of pellet in distilled water	Ameliorates neurobehavioral alterations of Alzheimer’s	VEDAGIRI &THANGARAHAN (2016VEDAGIRI, A.; THANGARAHAN, S. Mitigating effect of chrysin loaded solid lipid nanoparticles against Amyloid β25-35 induced oxidative stress in rat hippocampal region: An efficient formulation approach for Alzheimer’s disease. Neuropeptides, v.58, p.111-125, 2016. Available from: <Available from: https://doi.org/10.1016/j.npep.2016.03.002 >. Accessed: Dec. 12, 2022. doi: 10.1016/j.npep.2016.03.002. https://doi.org/10.1016/j.npep.2016.03.0... )
Dissolution of chrysin in ethanol + Recrystallizatedβ-cyclodextrin dissolved in H₂O with continuous stirring + Crystallization in refrigerator + Vacuum filtration + Drying	Antioxidant, antimicrobial and anti-tumor activity	ZHU et al. (2016ZHU, Z. et al. Inclusion of chrysin in β-cyclodextrin and its biological activities. Journal of Drug Delivery Science and Technology, v.31, p.176-186, 2016. Available from: <Available from: https://doi.org/10.1016/j.jddst.2016.01.002 >. Accessed: Dec. 09, 2022. doi: 10.1016/j.jddst.2016.01.002. https://doi.org/10.1016/j.jddst.2016.01.... )
Dissolution with PLGA-PEG tri-block copolymer in DCM-methanol + Agitation + PVA + sonication + Vacuum vaporization of the solvent + Centrifugation + Washing with dH₂O + Lyophilization	Possible aplicattion in tissue regeneration	FIROUZI-AMANDI et al. (2018FIROUZI-AMANDI, A. et al. Chrysin-nanoencapsulated PLGA-PEG for macrophage repolarization: Possible application in tissue regeneration. Biomedicine & Pharmacotherapy, v.105, p.773-780, 2018. Available from: <Available from: https://doi.org/10.1016/j.biopha.2018.06.037 >. Accessed: Dec. 08, 2022. doi: 10.1016/j.biopha.2018.06.037. https://doi.org/10.1016/j.biopha.2018.06... )
Addition in dozorubicin/(PLGA-co-PMAA) copolymer + Sonication + PVA and agitation + Centrifugation + Washing with dH₂O and centrifugation	Anticancer effect in lung epithelial cancer cell lines	JABBARI et al. (2018JABBARI, S. et al. Doxorubicin and chrysin combination chemotherapy with novel pH-responsive poly [(lactide-co-glycolic acid)-block-methacrylic acid] nanoparticle. Journal of Drug Delivery Science and Technology, v.46, p.129-137, 2018. Available from: <Available from: https://doi.org/10.1016/j.jddst.2018.05.006 >. Accessed: Dec. 08, 2022. doi: 10.1016/j.jddst.2018.05.006. https://doi.org/10.1016/j.jddst.2018.05.... )
Dissolution of carboxymethyl cellulose in dH₂O + Addition of chrysin dissolved in DMSO + Addition of Chitosan + Agitation + Addition of nano-hydroxyapatite + Agitation + Addition of acetic acid + Solution cast into plate + Lyophilization	Mesenchymal stem cell proliferation and osteoblast differentiation	MENON et al. (2018MENON, A. H. et al. Sustained release of chrysin from chitosan-based scaffolds promotes mesenchymal stem cell proliferation and osteoblast differentiation. Carbohydrate Polymers, v.195, p.356-367, 2018. Available from: <Available from: https://pubmed.ncbi.nlm.nih.gov/29804987/ >. Accessed: Dec. 12, 2022. doi: 10.1016/j.carbpol.2018.04.115. https://pubmed.ncbi.nlm.nih.gov/29804987... )
Dissolution of chrysin in DMSO + Addition of chrysin solution to BSAnp in PBS + Agitation	Antitumor therapies	FERRADO et al. (2019FERRADO, J. B. et al. Formation and characterization of self-assembled bovine serum albumin nanoparticles as chrysin delivery systems. Colloids and Surfaces B: Biointerfaces, v.173, p.43-51, 2019. Available from: <Available from: https://doi.org/10.1016/j.colsurfb.2018.09.046 >. Accessed: Dec. 08, 2022. doi: 10.1016/j.colsurfb.2018.09.046. https://doi.org/10.1016/j.colsurfb.2018.... )
Dissolution with poly(ε-caprolactone), pomegranate oil, and sorbitanmonostearate in acetone + Addition to the aqueous phase (polysorbate H₂O) with magnetic stirring + Acetone evaporation by rotary evaporator + Concentration of suspensions under reduced pressure	Ameliorates neurobehavioral alterations of Alzheimer’s disease in mice	GIACOMELI et al. (2020GIACOMELI, R. et al. Chrysin loaded lipid-core nanocapsules ameliorates neurobehavioral alterations induced by β-amyloid1-42 in aged female mice. Behavioural Brain Research, v.390, 2020. Available from: <Available from: https://doi.org/10.1016/j.bbr.2020.112696 >. Accessed: Dec. 09, 2022. doi: 10.1016/j.bbr.2020.112696. https://doi.org/10.1016/j.bbr.2020.11269... )
Dissolution of chrysin and curcumine in PLGA/PEG + Magnetic stirring + Electrospinning + Nfs drying in a vacuum oven	Effect on T47D breast cancer cells	RASOULI et al. (2020RASOULI, S. et al. Synergistic anticancer effects of electrospun nanofiber-mediated codelivery of curcumin and chrysin: Possible application in prevention of breast cancer local recurrence. Journal of Drug Delivery Science and Technology, v.55, 2020. Available from: <Available from: https://doi.org/10.1016/j.jddst.2019.101402 >. Accessed: Dec. 12, 2022. doi: 10.1016/j.jddst.2019.101402. https://doi.org/10.1016/j.jddst.2019.101... )
Dissolution of chrysin and PLGA in acetone + Mix with PVA + Centrifugation + Lyophilization	Attenuation of allergic asthma	ROY et al. (2020ROY, S. et al. Chrysin-loaded PLGA attenuates OVA-induced allergic asthma by modulating TLR/NF-κB/NLRP3 axis. Nanomedicine: Nanotechnology, Biology, and Medicine, v.30, 2020. Available from: <Available from: https://pubmed.ncbi.nlm.nih.gov/32853785/ >. Accessed: Dec. 12, 2022. doi: 10.1016/j.nano.2020.102292. https://pubmed.ncbi.nlm.nih.gov/32853785... )
Dissolution with PLGA, Labrafac PG and phosphatidylcholine in acetone + Addition dropwise to an aqueous solution of tween 80 placed on a magnetic stirrer + Evaporation of the organic solvent	Anti-glycemic and anti-hyperlipidemic	EL-HUSSIEN et al. (2021EL-HUSSIEN, D. et al. Chrysinnanocapsules with dual anti-glycemic and anti-hyperlipidemic effects: Chemometric optimization, physicochemical characterization and pharmacodynamic assessment. International Journal of Pharmaceutics, v.592, 2021. Available from: <Available from: https://doi.org/10.1016/j.ijpharm.2020.120044 >. Accessed: Dec. 09, 2022. doi: 10.1016/j.ijpharm.2020.120044. https://doi.org/10.1016/j.ijpharm.2020.1... )
Dissolution of chrysin in DMSO + Agitation + Addition to Au nanocapsules solution + Agitation + Centrifugation	Antioxidant, anti-microbial and cytotoxic	JASIM et al. (2022)JASIM, A. J. et al. Preliminary trials of the gold nanoparticles conjugated chrysin: An assessment of anti-oxidant, anti-microbial, and in vitro cytotoxic activities of a nanoformulated flavonoid. Nanotechnology Reviews, v.11, p.2726-2741, 2022. Available from: <Available from: https://www.degruyter.com/document/doi/10.1515/ntrev-2022-0153/html >. Accessed: Dec. 12, 2022. doi: 10.1515/ntrev-2022-0153 https://www.degruyter.com/document/doi/1...
Dissolution in DCM and acetone + Emulsification with PVA + Centrifugation + Supernadant discard + Drying and pelletizing	Antioxidant, antidiabetic and antiglycating	KHALID &NASEEM (2022KHALID, A.; NASEEM, I. Antidiabetic and antiglycating potential of chrysin is enhanced after nano formulation: An in vitro approac. Journal of Molecular Structure, v.1261, n.5, 2022. Available from: <Available from: https://ui.adsabs.harvard.edu/abs/2022JMoSt126132906K/abstract >. Accessed: Dec. 08, 2022. doi: 10.1016/j.molstruc.2022.132906. https://ui.adsabs.harvard.edu/abs/2022JM... )
Chrysin and metformin mixed with polymer + Placed in rotary flask + Addition of DCM + Sonication + Solvent evaporation + Hydration + Filtration	Effect in breast cancer in mice	LUO et al. (2022LUO, D. et al. MPEG-PCL nanomicelles platform for synergistic metformin and chrysin delivery to breast cancer in mice. Anti-Cancer Agents in Medicinal Chemistry, v.2, p.280-293, 2022. Available from: <Available from: https://pubmed.ncbi.nlm.nih.gov/34165412/ >. Accessed: Dec. 12, 2022. doi: 10.2174/1871520621666210623092725. https://pubmed.ncbi.nlm.nih.gov/34165412... )

Brasil

Brasil

Encapsulação do flavonoide crisina: uma revisão sobre as metodologias utilizadas e potencial biológico

RESUMO: