Name: Autor destacado: Desarrollo y caracterización de micropartículas ecológicas basadas en lignina para mejorar la administración de bioflavonoides
Uploaded: 2024-03-01T14:05:00
Description: Watch this Scientific Journal Video about Author Spotlight: Development and Characterization of Eco-Friendly Lignin-Based Microparticles for Enhanced Delivery of Bioflavonoids at JoVE.com

Este estudio contó con el apoyo del Fondo Científico Búlgaro en virtud del contrato n.º KΠ-06 H59/3 y del proyecto científico n.º 07/2023 FVM, Universidad de Trakia.

1. Síntesis de micropartículas de lignina
<ol><li>Prepare una solución acuosa de lignina alcalina de 50 mg/ml disolviendo 2,5 g de lignina alcalina en 50 ml de agua ultrapura en un agitador magnético.</li>
	<li>Prepare la solución de Tween 80 al 1% disolviendo 1 mL de Tween 80 en 100 mL de agua ultrapura.</li>
	<li>Prepare una solución 2 M deHNO3 diluyendo 6,65 mL deHNO3 al 67% (densidad = 1,413 g/mL) con agua ultrapura hasta un volumen final de 50 mL.</li>
	<li>Agregue lent...

Síntesis de partículas micro/submicrónicas de lignina para la liberación de bioflavonoides

<ol>
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A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Opportunities+and+challenges+for+lignin+valorization+in+food+packaging,+antimicrobial,+and+agricultural+applications.">Opportunities and challenges for lignin valorization in food packaging, antimicrobial, and agricultural applications.</a> Biomacromolecules. 24 (3), 1065-1077 (2023).</li><li>Aadil, K., Barapatre, A., Jha, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+and+characterization+of+Acacia+lignin-gelatin+film+for+its+possible+application+in+food+packaging.">Synthesis and characterization of Acacia lignin-gelatin film for its possible application in food packaging.</a> Bioresour. 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K., Wyrobnik, T. A., Lam, A. T. -. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Emerging+trends+in+biodegradable+microcarriers+for+therapeutic+applications.">Emerging trends in biodegradable microcarriers for therapeutic applications.</a> Polymers. 15 (6), 1487 (2023).</li><li>Figueiredo, P., Lintinen, K., Hirvonen, J. T., Kostiainen, M. A., Santos, H. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Properties+and+chemical+modifications+of+lignin:+Towards+lignin-based+nanomaterials+for+biomedical+applications.">Properties and chemical modifications of lignin: Towards lignin-based nanomaterials for biomedical applications.</a> Prog. Mater. Sci. 93, 233-269 (2018).</li><li>Tang, Q., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lignin-based+nanoparticles:+a+review+on+their+preparations+and+applications.">Lignin-based nanoparticles: a review on their preparations and applications.</a> Polymers. 12 (11), 2471 (2020).</li><li>Zhao, W., Simmons, B., Singh, S., Ragauskas, A., Cheng, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=From+lignin+association+to+nano-/micro-particle+preparation:+extracting+higher+value+of+lignin.">From lignin association to nano-/micro-particle preparation: extracting higher value of lignin.</a> Green Chemistry. 18 (21), 5693-5700 (2016).</li><li>Stewart, H., Golding, M., Matia-Merino, L., Archer, R., Davies, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Manufacture+of+lignin+microparticles+by+anti-solvent+precipitation:+Effect+of+preparation+temperature+and+presence+of+sodium+dodecyl+sulfate.">Manufacture of lignin microparticles by anti-solvent precipitation: Effect of preparation temperature and presence of sodium dodecyl sulfate.</a> Food Res Int. 66, 93-99 (2014).</li><li>Beisl, S., Friedl, A., Miltner, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lignin+from+micro-+to+nanosize:+Applications.">Lignin from micro- to nanosize: Applications.</a> Int. 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Entre los principales aspectos críticos de las metodologías modernas de síntesis para el diseño de formulaciones de fármacos portadores basados en biopolímeros se encuentra la aplicación de reactivos orgánicos peligrosos -disolventes volátiles e inflamables, como el tetrahidrofurano, la acetona, el metanol e incluso el DMSO en altas concentraciones- lo que limita su aplicabilidad en biomedicina, industria farmacéutica y tecnología alimentaria debido a la manifestación de posibles efectos tóxicos<sup class="x...

Hoy en día, la inclinación hacia biopolímeros como la celulosa, el quitosano, el colágeno, el dextrano, la gelatina y la lignina como precursores para el diseño de portadores micro/submicrónicos con tamaño, propiedades fisicoquímicas y biofuncionalidades personalizables ha aumentado en las industrias biomédica, farmacéutica y de tecnología alimentaria debido a su aplicabilidad en ingeniería de tejidos, bioimpresión 3D, in vitro plataformas de modelado de enfermedades, industria de empaque, preparación de emulsiones y entrega de nutrientes, entre otros 1,2,3.
Los nuevos estudios destacan los aspectos de los hidrogeles a base de lignina, así como de las micro y nanoformulaciones4 como vehículos ventajosos utilizados para los materiales de envasado de alimentos5, el almacenamiento de energía6, los cosméticos7, los estabilizadores térmicos/ligeros, los materiales reforzados y las matrices portadoras de fármacos8 para la administración de moléculas hidrofóbicas, la mejora de las barreras UV9, como agentes de refuerzo en nanocompuestos, y como alternativa a las nanopartículas inorgánicas debido a algunos problemas de seguridad recientes 10,11,12. La razón detrás de esta tendencia es la biocompatibilidad, biodegradabilidad y no toxicidad del heterobiopolímero natural, así como sus bioactividades comprobadas de potencial antioxidante de lignina y actividades antiproliferativas y antimicrobianas 13,14,15,16,17.
La literatura científica reporta varios métodos para la síntesis (autoensamblaje, precipitación anti-solvente, precipitación ácida y cambio de solvente)18 y la caracterización de formulaciones a micro / nano escala basadas en lignina, incluida la aplicación de solventes costosos o dañinos como tetrahidrofurano (THF), dimetilsulfóxido (DMSO), N,N-dimetilformamida (DMF) y acetona, y procesos complicados, indirectos y tediosos que utilizan una gran cantidad de equipos y sustancias tóxicas 12,19,20.
Para superar estas últimas desventajas, los siguientes protocolos presentan metodologías novedosas para la síntesis de partículas micro/submicrónicas basadas en lignina utilizando disolventes baratos y ecológicos; Procesos fáciles, sencillos, rápidos y sensibles que requieren poco equipo, sustancias no tóxicas y métodos sencillos para su caracterización y la determinación de la capacidad de encapsulación hacia compuestos bioactivos poco solubles en agua y el potencial de liberación in vitro de las matrices de lignina. Los métodos de producción a escala de laboratorio presentados son ventajosos para la fabricación de portadores de lignina funcionales con tamaños ajustables, alta capacidad de encapsulación y comportamiento de liberación in vitro sostenible utilizando procedimientos de caracterización simples y productos químicos ecológicos que pueden encontrar aplicación en diversas áreas de las ciencias biomédicas y la tecnología de los alimentos. Se aplicaron dos flavonoides como moléculas diana encapsuladas en las partículas de lignina: morina, en las micropartículas, y quercetina, en las partículas submicrónicas. La diferencia en las estructuras de ambos flavonoides es solo la posición del segundo grupo -OH en el anillo aromático B: el grupo -OH está en la posición 2' en morina y en la posición 3' en quercetina, por lo que ambos compuestos orgánicos son isómeros posicionales. Este último hecho supone un comportamiento similar de ambos compuestos naturales bioactivos en los procesos de encapsulación y/o liberación.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>automatic-cell counter</td>
			<td>EVE, NanoEnTek</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Citric acid</td>
			<td>Sigma</td>
			<td>251275</td>
			<td>&#160;ACS reagent, &#8805;99.5%</td>
		</tr>
		<tr>
			<td>digital water bath</td>
			<td>Memmert</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Eppendorf tubes, 1.5-2 mL</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Ethanol</td>
			<td>Sigma</td>
			<td>34852-M</td>
			<td>absolute, suitable for HPLC, &#8805;99.8%</td>
		</tr>
		<tr>
			<td>Folin&#8211;Ciocalteu&#8217;s phenol reagent</td>
			<td>Sigma</td>
			<td>F9252</td>
			<td></td>
		</tr>
		<tr>
			<td>&#160;freeze dryer</td>
			<td>Biobase</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>gallic acid</td>
			<td>Sigma-</td>
			<td>BCBW7577</td>
			<td>monohydrate</td>
		</tr>
		<tr>
			<td>HCl</td>
			<td>Sigma</td>
			<td>258148</td>
			<td>ACS reagent, 37%</td>
		</tr>
		<tr>
			<td>HNO3</td>
			<td>Sigma</td>
			<td>438073</td>
			<td>&#160;ACS reagent, 70%</td>
		</tr>
		<tr>
			<td>lignin, alkali</td>
			<td>Sigma</td>
			<td>370959</td>
			<td></td>
		</tr>
		<tr>
			<td>morin</td>
			<td>Sigma</td>
			<td>PHL82601</td>
			<td></td>
		</tr>
		<tr>
			<td>NaCl</td>
			<td>Sigma</td>
			<td>S9888</td>
			<td>ACS reagent, &#8805;99.0%</td>
		</tr>
		<tr>
			<td>Na2CO3</td>
			<td>Sigma</td>
			<td>223530</td>
			<td>powder, &#8805;99.5%, ACS reagent</td>
		</tr>
		<tr>
			<td>NaOH</td>
			<td>Sigma</td>
			<td>655104</td>
			<td>reagent grade, 97%, powder</td>
		</tr>
		<tr>
			<td>orbital shaker</td>
			<td>IKA</td>
			<td>KS 130 basic</td>
			<td></td>
		</tr>
		<tr>
			<td>pH-meter</td>
			<td>Consort</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>phosphate-buffered saline (PBS)</td>
			<td>Sigma</td>
			<td>RNBH7571</td>
			<td></td>
		</tr>
		<tr>
			<td>Quercetin hydrate</td>
			<td>Sigma</td>
			<td>STBG3815V</td>
			<td></td>
		</tr>
		<tr>
			<td>statistical software for Excel</td>
			<td>Microsoft Corporation</td>
			<td></td>
			<td>XLSTAT&#160; Version 2022.4.5.</td>
		</tr>
		<tr>
			<td>Tween 80</td>
			<td>Sigma</td>
			<td>P8074</td>
			<td>BioXtra, viscous liquid</td>
		</tr>
		<tr>
			<td>ultracentrifuge</td>
			<td>Hermle</td>
			<td>Z 326 K</td>
			<td></td>
		</tr>
		<tr>
			<td>Ultrapure water system</td>
			<td>Adrona</td>
			<td>INTEGRITY+</td>
			<td></td>
		</tr>
		<tr>
			<td>ultrasound homogenizer</td>
			<td>Bandelin Sonopuls</td>
			<td>HD 2070</td>
			<td></td>
		</tr>
		<tr>
			<td>UV/Vis spectrophotometer</td>
			<td>Hach-Lange</td>
			<td>DR 5000</td>
			<td></td>
		</tr>
	</tbody>
</table>

green synthesis, characterization, encapsulation, and measurement of the release potential of novel alkali lignin micro-/submicron particles

La aplicabilidad de la micro y nanotecnología de biopolímeros en la tecnología humana, veterinaria, farmacéutica y alimentaria está creciendo rápidamente debido al gran potencial de las partículas basadas en biopolímeros como sistemas portadores eficaces. El uso de la lignina como biomatriz básica de heteropolímeros para el diseño de formulaciones micro / submicrónicas innovadoras permite el logro de una mayor biocompatibilidad y ofrece varios grupos funcionales activos que presentan oportunidades para la personalización de las propiedades fisicoquímicas y bioactividades de las formulaciones para diversas aplicaciones. El objetivo del presente estudio fue desarrollar una metodología simple y ecológica para la síntesis de partículas de lignina con tamaño micro y submicrónico; evaluar sus características fisicoquímicas, espectrales y estructurales; y examinar su capacidad para la encapsulación de moléculas biológicamente activas y su potencial para la liberación in vitro de bioflavonoides en medios gastrointestinales simulados. Las metodologías presentadas aplican solventes baratos y verdes; Procesos fáciles, sencillos, rápidos y sensibles que requieren poco equipo, sustancias no tóxicas y métodos sencillos para su caracterización, la determinación de la capacidad de encapsulación hacia los compuestos bioactivos poco solubles en agua morina y quercetina, y el potencial de liberación in vitro de las matrices de lignina.

Nowadays inclination towards biopolymers such as cellulose, chitosan, collagen, dextran, gelatin, and lignin as precursors for the design of micro-/submicron carriers with customizable size, physicochemical properties, and biofunctionalities has increased in the biomedical, pharmaceutical, and food technology industries due to their applicability in tissue engineering, 3D bioprinting, in vitro disease modeling platforms, packaging industry, emulsion preparation, and nutrient delivery among others1,2,3.
Novel studies highlight the aspects of lignin-based hydrogels as well as micro- and nano- formulations4 as advantageous vehicles used for food packaging materials5, energy storage6, cosmetics7, thermal/light stabilizers, reinforced materials, and drug-carrier matrices8 for the delivery of hydrophobic molecules, improvement of UV barriers9, as reinforcing agents in nanocomposites, and as an alternative to inorganic nanoparticles due to some recent safety issues10,11,12. The reason behind this tendency is the biocompatibility, biodegradability, and non-toxicity of the natural hetero biopolymer, as well as its proven bioactivities of lignin-antioxidant potential and radical scavenging, anti-proliferative, and antimicrobial activities13,14,15,16,17.
Scientific literature reports various methods for synthesis (self-assembly, anti-solvent precipitation, acid precipitation, and solvent shifting)18 and characterization of lignin-based micro-/nano- scaled formulations, including the application of expensive or harmful solvents such as tetrahydrofuran (THF), dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), and acetone, and complicated, indirect, and tedious processes that use a lot of equipment and toxic substances12,19,20.
To overcome the latter disadvantages, the following protocols present novel methodologies for the synthesis of lignin-based micro-/submicron particles using cheap and green solvents; easy, straightforward, quick, and sensitive processes requiring little equipment, non-toxic substances, and simple methods for their characterization and the determination of encapsulation capacity towards poorly water-soluble bioactive compounds and in vitro release potential of the lignin matrices. The presented lab-scale production methods are advantageous for the manufacture of functional lignin carriers with tunable sizes, high encapsulation capacity, and sustainable in vitro release behavior utilizing simple characterization procedures and eco-friendly chemicals that can find application in various areas of biomedical sciences and food technology. Two flavonoids were applied as target molecules encapsulated into the lignin particles: morin-into the microparticles, and quercetin-into the submicron particles. The difference in the structures of both flavonoids Is only the position of the second -OH group in the B-aromatic ring: the -OH group is on the 2&#39; position in morin and on the 3&#39; position in quercetin, thus both organic compounds are positional isomers. The latter fact presumes similar behavior of both bioactive natural compounds in the processes of encapsulation and/or release.

Autor destacado: Desarrollo y caracterización de micropartículas ecológicas basadas en lignina para mejorar la administración de bioflavonoides

Síntesis, caracterización, encapsulación y medición del potencial de liberación de nuevas partículas micro/submicrónicas de lignina alcalina

The objective of this research was to create a straightforward and environmentally friendly process to produce small lignin particles. The study aimed to analyze their physical, chemical, and structural properties, as well as investigate their ability to encapsulate and release bioflavonoids in stimulated gastrointestinal environments. Our method synthesizes lignin based particles using cheap and green solvents.The process is easy, quick, and requires minimal equipment and non-toxic substances. It also has simple methods for characterization, encapsulation, capacity determination, and in-vitro release potential of poorly water soluble bioactive compounds. The innovative biopolymer microparticles are suitable for oral administration due to the lower risk of gastric irritation.The submicron particles, due to the small size and significant release potential, could be applied as injectable formulations.

Se ejecutó una técnica de precipitación anti-solvente para producir partículas micro y submicrónicas de lignina alcalina. Una solución acuosa de ácido inorgánico-ácido nítrico/ácido orgánico-ácido cítrico diluido se dispersó en una solución acuosa de lignina alcalina, enriquecida con un tensioactivo/etanol respetuoso con el medio ambiente, lo que dio lugar a la precipitación gradual del soluto biopolímero y, tras la sonicación, se produjo finalmente una suspensión de partículas compactas micro/submic...

Watch this Scientific Journal Video about Author Spotlight: Development and Characterization of Eco-Friendly Lignin-Based Microparticles for Enhanced Delivery of Bioflavonoids at JoVE.com

Describimos metodologías novedosas y sencillas de síntesis y caracterización de micro y submicrónicas de lignina biocompatibles. Estas formulaciones proporcionan un enfoque fácil para la utilización del heteropolímero, así como una alternativa para el diseño racional de matrices portadoras multifuncionales con potencial aplicabilidad en biomedicina, tecnología farmacéutica e industria alimentaria.

The applicability of biopolymer micro-/nano- technology in human, veterinary medicine, pharmaceutical, and food technology is rapidly growing due to the ...

El objetivo de esta investigación fue crear un proceso sencillo y respetuoso con el medio ambiente para producir pequeñas partículas de lignina. El estudio tuvo como objetivo analizar sus propiedades físicas, químicas y estructurales, así como investigar su capacidad para encapsular y liberar bioflavonoides en ambientes gastrointestinales estimulados. Nuestro método sintetiza partículas a base de lignina utilizando disolventes baratos y ecológicos.El proceso es fácil, rápido y requiere un equipo mínimo y sustancias no tóxicas. También cuenta con métodos sencillos para la caracterización, encapsulación, determinación de la capacidad y potencial de liberación in vitro de compuestos bioactivos poco solubles en agua. Las innovadoras micropartículas de biopolímero son adecuadas para la administración oral debido al menor riesgo de irritación gástrica.Las partículas submicrónicas, debido a su pequeño tamaño y significativo potencial de liberación, podrían aplicarse como formulaciones inyectables.

green-synthesis-characterization-encapsulation-measurement-release

Research

JoVE Journal

Chemistry

Green Synthesis, Characterization, Encapsulation, and Measurement of the Release Potential of Novel Alkali Lignin Micro-/Submicron Particles

The applicability of biopolymer micro-/nano- technology in human, veterinary medicine, pharmaceutical, and food technology is rapidly growing due to the great potential of biopolymer-based particles as effective carrier systems. The use of lignin as a basic heteropolymer biomatrix for the design of innovative micro-/submicron formulations allows the achievement of increased biocompatibility and offers various active functional groups presenting opportunities for customization of the physicochemical properties and bioactivities of the formulations for diverse applications. The aim of the present study was to develop a simple and ecofriendly methodology for the synthesis of lignin particles with micro- and submicron size; to evaluate their physicochemical, spectral, and structural characteristics; and to examine their capacity for encapsulation of biologically active molecules and potential for in vitro release of bioflavonoids in simulated gastrointestinal media. The presented methodologies apply cheap and green solvents; easy, straightforward, quick, and sensitive processes requiring little equipment, non-toxic substances, and simple methods for their characterization, the determination of encapsulation capacity towards the poorly water-soluble bioactive compounds morin and quercetin, and the in vitro release potential of the lignin matrices.

We describe novel, simple methodologies of synthesis and characterization of biocompatible lignin micro- and submicron particles. These formulations provide a facile approach for the utilization of the heteropolymer, as well as an alternative for the rational design of multifunctional carrier matrices with potential applicability in biomedicine, pharmaceutical technology, and the food industry.