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In Vitro Cell Behavior and Antibiotic Activity under Sustained Release of Doxycycline-Loaded Poly(lactic-co-glycolic acid) Microspheres

The state-of-the-art sustained drug delivery systems are related to features to improve pharmacological transport through a controlled ratio between drug release and the desired therapeutic effect. Microspheres of biodegradable polymers, such as poly(lactic-co-glycolic acid) (PLGA), play an importan...

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Autores principales: Pedrini, Flavia, Nazato, Virgínia S., Hausen, Moema A., Komatsu, Daniel, Peña, Stela S., Almeida, Ana Lídia M., Pirola, Fernanda J. C., Françoso, Marina P., Duek, Eliana A. R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9311981/
https://www.ncbi.nlm.nih.gov/pubmed/35884199
http://dx.doi.org/10.3390/antibiotics11070945
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author Pedrini, Flavia
Nazato, Virgínia S.
Hausen, Moema A.
Komatsu, Daniel
Peña, Stela S.
Almeida, Ana Lídia M.
Pirola, Fernanda J. C.
Françoso, Marina P.
Duek, Eliana A. R.
author_facet Pedrini, Flavia
Nazato, Virgínia S.
Hausen, Moema A.
Komatsu, Daniel
Peña, Stela S.
Almeida, Ana Lídia M.
Pirola, Fernanda J. C.
Françoso, Marina P.
Duek, Eliana A. R.
author_sort Pedrini, Flavia
collection PubMed
description The state-of-the-art sustained drug delivery systems are related to features to improve pharmacological transport through a controlled ratio between drug release and the desired therapeutic effect. Microspheres of biodegradable polymers, such as poly(lactic-co-glycolic acid) (PLGA), play an important role in these approaches, directing the release in a specific region of interest. In this way, the encapsulation of doxycycline (DOX) as a microbial agent turns the PLGA microspheres into a potential device for the treatment of topic oral diseases. Thus, this work aimed to produce DOX-loaded PLGA microspheres and see how they interfered with mesenchymal stem cell viability and in the sustained release in antimicrobial assays. Scanning electron microscopy showed the spherical microstructured pattern, revealing assorted sized distribution, with major diameters ranging 1–3 µm. The encapsulation efficiency presented a mean of 80% in both methods to obtain the microspheres (sonication and magnetic rotation). The DOX release test revealed a gradual and continuous profile of 30–40% between 120 and 168 h. Mesenchymal stem cells cultured in PLGA with or without DOX at several concentrations revealed no effect on the cell metabolic activity. Striking morphology changes were observed by confocal microscopy after 1 to 3 days under culture. The live/dead assay indicated that when microsphere densities were increased (from 10 to 100 µg/mL) cultured cells presented an internalized pattern of microspheres in both groups of PLGA containing DOX or not, while slight cell death signals were identified nearby microsphere clusters. Microbiological assays performed by the agar diffusion test pointed out that an inhibition zone was identified in Staphylococcus aureus (S. aureus) cultures at earlier times of DOX release. Despite the well-known use of PLGA as a drug delivery vehicle, when synthesized with DOX, it presents both characteristics of the desired treatment to prevent healthy tissue damage while avoiding bacterial growth in a microenvironment with anatomical features, such as grooves, projections, and other tough conditions that favor the development of oral diseases.
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spelling pubmed-93119812022-07-26 In Vitro Cell Behavior and Antibiotic Activity under Sustained Release of Doxycycline-Loaded Poly(lactic-co-glycolic acid) Microspheres Pedrini, Flavia Nazato, Virgínia S. Hausen, Moema A. Komatsu, Daniel Peña, Stela S. Almeida, Ana Lídia M. Pirola, Fernanda J. C. Françoso, Marina P. Duek, Eliana A. R. Antibiotics (Basel) Article The state-of-the-art sustained drug delivery systems are related to features to improve pharmacological transport through a controlled ratio between drug release and the desired therapeutic effect. Microspheres of biodegradable polymers, such as poly(lactic-co-glycolic acid) (PLGA), play an important role in these approaches, directing the release in a specific region of interest. In this way, the encapsulation of doxycycline (DOX) as a microbial agent turns the PLGA microspheres into a potential device for the treatment of topic oral diseases. Thus, this work aimed to produce DOX-loaded PLGA microspheres and see how they interfered with mesenchymal stem cell viability and in the sustained release in antimicrobial assays. Scanning electron microscopy showed the spherical microstructured pattern, revealing assorted sized distribution, with major diameters ranging 1–3 µm. The encapsulation efficiency presented a mean of 80% in both methods to obtain the microspheres (sonication and magnetic rotation). The DOX release test revealed a gradual and continuous profile of 30–40% between 120 and 168 h. Mesenchymal stem cells cultured in PLGA with or without DOX at several concentrations revealed no effect on the cell metabolic activity. Striking morphology changes were observed by confocal microscopy after 1 to 3 days under culture. The live/dead assay indicated that when microsphere densities were increased (from 10 to 100 µg/mL) cultured cells presented an internalized pattern of microspheres in both groups of PLGA containing DOX or not, while slight cell death signals were identified nearby microsphere clusters. Microbiological assays performed by the agar diffusion test pointed out that an inhibition zone was identified in Staphylococcus aureus (S. aureus) cultures at earlier times of DOX release. Despite the well-known use of PLGA as a drug delivery vehicle, when synthesized with DOX, it presents both characteristics of the desired treatment to prevent healthy tissue damage while avoiding bacterial growth in a microenvironment with anatomical features, such as grooves, projections, and other tough conditions that favor the development of oral diseases. MDPI 2022-07-14 /pmc/articles/PMC9311981/ /pubmed/35884199 http://dx.doi.org/10.3390/antibiotics11070945 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pedrini, Flavia
Nazato, Virgínia S.
Hausen, Moema A.
Komatsu, Daniel
Peña, Stela S.
Almeida, Ana Lídia M.
Pirola, Fernanda J. C.
Françoso, Marina P.
Duek, Eliana A. R.
In Vitro Cell Behavior and Antibiotic Activity under Sustained Release of Doxycycline-Loaded Poly(lactic-co-glycolic acid) Microspheres
title In Vitro Cell Behavior and Antibiotic Activity under Sustained Release of Doxycycline-Loaded Poly(lactic-co-glycolic acid) Microspheres
title_full In Vitro Cell Behavior and Antibiotic Activity under Sustained Release of Doxycycline-Loaded Poly(lactic-co-glycolic acid) Microspheres
title_fullStr In Vitro Cell Behavior and Antibiotic Activity under Sustained Release of Doxycycline-Loaded Poly(lactic-co-glycolic acid) Microspheres
title_full_unstemmed In Vitro Cell Behavior and Antibiotic Activity under Sustained Release of Doxycycline-Loaded Poly(lactic-co-glycolic acid) Microspheres
title_short In Vitro Cell Behavior and Antibiotic Activity under Sustained Release of Doxycycline-Loaded Poly(lactic-co-glycolic acid) Microspheres
title_sort in vitro cell behavior and antibiotic activity under sustained release of doxycycline-loaded poly(lactic-co-glycolic acid) microspheres
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9311981/
https://www.ncbi.nlm.nih.gov/pubmed/35884199
http://dx.doi.org/10.3390/antibiotics11070945
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