The Incorporation of CBD into Biodegradable DL-Lactide/Glycolide Copolymers Creates a Persistent Antibacterial Environment: An In Vitro Study on <i>Streptococcus mutans</i> and <i>Staphylococcus aureus</i>

<b>Background</b>: Cannabidiol (CBD) is a natural compound from the <i>Cannabis sativa</i> L. plant, which has anti-inflammatory, anti-nociceptive, neuroprotective, and antibacterial activities. <b>Objective</b>: The aim of this study was to develop a sustained-re...

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Main Authors: Ronit Vogt Sionov, Ahmad Siag, Emma Theresa Mersini, Natalya M. Kogan, Tatiana Alkhazov, Igor Koman, Praveen Rowlo, Vitaly Gutkin, Menachem Gross, Doron Steinberg
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/4/463
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author Ronit Vogt Sionov
Ahmad Siag
Emma Theresa Mersini
Natalya M. Kogan
Tatiana Alkhazov
Igor Koman
Praveen Rowlo
Vitaly Gutkin
Menachem Gross
Doron Steinberg
author_facet Ronit Vogt Sionov
Ahmad Siag
Emma Theresa Mersini
Natalya M. Kogan
Tatiana Alkhazov
Igor Koman
Praveen Rowlo
Vitaly Gutkin
Menachem Gross
Doron Steinberg
author_sort Ronit Vogt Sionov
collection DOAJ
description <b>Background</b>: Cannabidiol (CBD) is a natural compound from the <i>Cannabis sativa</i> L. plant, which has anti-inflammatory, anti-nociceptive, neuroprotective, and antibacterial activities. <b>Objective</b>: The aim of this study was to develop a sustained-release device of CBD that can provide an antibacterial effect against the Gram-positive bacteria <i>Streptococcus mutans</i> and <i>Staphylococcus aureus</i> for extended periods of time. <b>Methods</b>: CBD was incorporated into the biodegradable PURASORB 5010 or PURASORB 7510 DL-lactide/glycolide polymers using either dimethylsulfoxide (DMSO) or acetone as the solvent, and the dried polymer scaffolds were exposed daily to a fresh culture of bacteria. The bacterial growth was determined daily by optical density, and the metabolic activity of biofilms was determined using the MTT assay. Biofilm formation on the polymer scaffolds was visualized by HR-SEM. Its anti-inflammatory effect was determined by measuring the IL-6 release from LPS-stimulated RAW 264.7 macrophages by ELISA. Cell cytotoxicity on normal Vero epithelial cells was determined by the MTT assay. The daily release of CBD was determined by gas chromatography–mass spectrometry (GC-MS). <b>Results</b>: PURASORB 5010/CBD scaffolds had antibacterial activity against <i>S. mutans</i> UA159, <i>S. aureus</i> ATCC25923, and a clinical isolate of a multidrug-resistant <i>S. aureus</i> (MDRSA CI-M) strain for the tested period of up to 17 days. PURASORB 7510/CBD scaffolds also had antibacterial activity, but overall, it was less effective than PURASORB 5010/CBD over time. The addition of PEG400 to the copolymers significantly increased the antibacterial activity of PURASORB 7510/CBD but not of PURASORB 5010/CBD. The daily release of CBD from the polymer scaffolds was sufficient to reduce the LPS-induced IL-6 secretion from RAW 264.7 macrophages, and importantly, it was not cytotoxic to either RAW 264.7 macrophages or Vero epithelial cells. The daily release of CBD was found to be between 1.12 and 9.43 µg/mL, which is far below the cytotoxic dose of 25 µg/mL. <b>Conclusions</b>: The incorporation of CBD into the biodegradable PURASORB 5010 can be used to prepare sustained-release devices for medical purposes where combined antibacterial and anti-inflammatory activities are desirable.
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spelling doaj-art-cf06ecae4cac4c1eb590f32a3c2874a92025-08-20T02:18:15ZengMDPI AGPharmaceutics1999-49232025-04-0117446310.3390/pharmaceutics17040463The Incorporation of CBD into Biodegradable DL-Lactide/Glycolide Copolymers Creates a Persistent Antibacterial Environment: An In Vitro Study on <i>Streptococcus mutans</i> and <i>Staphylococcus aureus</i>Ronit Vogt Sionov0Ahmad Siag1Emma Theresa Mersini2Natalya M. Kogan3Tatiana Alkhazov4Igor Koman5Praveen Rowlo6Vitaly Gutkin7Menachem Gross8Doron Steinberg9Faculty of Dental Medicine, Institute of Biomedical and Oral Research (IBOR), The Hebrew University of Jerusalem, Ein Kerem Campus, Jerusalem 9112102, IsraelFaculty of Dental Medicine, Institute of Biomedical and Oral Research (IBOR), The Hebrew University of Jerusalem, Ein Kerem Campus, Jerusalem 9112102, IsraelFaculty of Dental Medicine, Institute of Biomedical and Oral Research (IBOR), The Hebrew University of Jerusalem, Ein Kerem Campus, Jerusalem 9112102, IsraelInstitute of Personalized and Translational Medicine, Department of Molecular Biology, Ariel University, Ariel 4070000, IsraelInstitute of Personalized and Translational Medicine, Department of Molecular Biology, Ariel University, Ariel 4070000, IsraelInstitute of Personalized and Translational Medicine, Department of Molecular Biology, Ariel University, Ariel 4070000, IsraelFaculty of Dental Medicine, Institute of Biomedical and Oral Research (IBOR), The Hebrew University of Jerusalem, Ein Kerem Campus, Jerusalem 9112102, IsraelUnit for Nano Characterization, The Harvey M. Krueger Family Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Jerusalem 9190401, IsraelDepartment of Otolaryngology-Head and Neck Surgery, Hadassah Medical Center, Jerusalem 9112102, IsraelFaculty of Dental Medicine, Institute of Biomedical and Oral Research (IBOR), The Hebrew University of Jerusalem, Ein Kerem Campus, Jerusalem 9112102, Israel<b>Background</b>: Cannabidiol (CBD) is a natural compound from the <i>Cannabis sativa</i> L. plant, which has anti-inflammatory, anti-nociceptive, neuroprotective, and antibacterial activities. <b>Objective</b>: The aim of this study was to develop a sustained-release device of CBD that can provide an antibacterial effect against the Gram-positive bacteria <i>Streptococcus mutans</i> and <i>Staphylococcus aureus</i> for extended periods of time. <b>Methods</b>: CBD was incorporated into the biodegradable PURASORB 5010 or PURASORB 7510 DL-lactide/glycolide polymers using either dimethylsulfoxide (DMSO) or acetone as the solvent, and the dried polymer scaffolds were exposed daily to a fresh culture of bacteria. The bacterial growth was determined daily by optical density, and the metabolic activity of biofilms was determined using the MTT assay. Biofilm formation on the polymer scaffolds was visualized by HR-SEM. Its anti-inflammatory effect was determined by measuring the IL-6 release from LPS-stimulated RAW 264.7 macrophages by ELISA. Cell cytotoxicity on normal Vero epithelial cells was determined by the MTT assay. The daily release of CBD was determined by gas chromatography–mass spectrometry (GC-MS). <b>Results</b>: PURASORB 5010/CBD scaffolds had antibacterial activity against <i>S. mutans</i> UA159, <i>S. aureus</i> ATCC25923, and a clinical isolate of a multidrug-resistant <i>S. aureus</i> (MDRSA CI-M) strain for the tested period of up to 17 days. PURASORB 7510/CBD scaffolds also had antibacterial activity, but overall, it was less effective than PURASORB 5010/CBD over time. The addition of PEG400 to the copolymers significantly increased the antibacterial activity of PURASORB 7510/CBD but not of PURASORB 5010/CBD. The daily release of CBD from the polymer scaffolds was sufficient to reduce the LPS-induced IL-6 secretion from RAW 264.7 macrophages, and importantly, it was not cytotoxic to either RAW 264.7 macrophages or Vero epithelial cells. The daily release of CBD was found to be between 1.12 and 9.43 µg/mL, which is far below the cytotoxic dose of 25 µg/mL. <b>Conclusions</b>: The incorporation of CBD into the biodegradable PURASORB 5010 can be used to prepare sustained-release devices for medical purposes where combined antibacterial and anti-inflammatory activities are desirable.https://www.mdpi.com/1999-4923/17/4/463cannabidiolCBDsustained-release devicePLGA scaffoldsantibacterialantibiofilm
spellingShingle Ronit Vogt Sionov
Ahmad Siag
Emma Theresa Mersini
Natalya M. Kogan
Tatiana Alkhazov
Igor Koman
Praveen Rowlo
Vitaly Gutkin
Menachem Gross
Doron Steinberg
The Incorporation of CBD into Biodegradable DL-Lactide/Glycolide Copolymers Creates a Persistent Antibacterial Environment: An In Vitro Study on <i>Streptococcus mutans</i> and <i>Staphylococcus aureus</i>
Pharmaceutics
cannabidiol
CBD
sustained-release device
PLGA scaffolds
antibacterial
antibiofilm
title The Incorporation of CBD into Biodegradable DL-Lactide/Glycolide Copolymers Creates a Persistent Antibacterial Environment: An In Vitro Study on <i>Streptococcus mutans</i> and <i>Staphylococcus aureus</i>
title_full The Incorporation of CBD into Biodegradable DL-Lactide/Glycolide Copolymers Creates a Persistent Antibacterial Environment: An In Vitro Study on <i>Streptococcus mutans</i> and <i>Staphylococcus aureus</i>
title_fullStr The Incorporation of CBD into Biodegradable DL-Lactide/Glycolide Copolymers Creates a Persistent Antibacterial Environment: An In Vitro Study on <i>Streptococcus mutans</i> and <i>Staphylococcus aureus</i>
title_full_unstemmed The Incorporation of CBD into Biodegradable DL-Lactide/Glycolide Copolymers Creates a Persistent Antibacterial Environment: An In Vitro Study on <i>Streptococcus mutans</i> and <i>Staphylococcus aureus</i>
title_short The Incorporation of CBD into Biodegradable DL-Lactide/Glycolide Copolymers Creates a Persistent Antibacterial Environment: An In Vitro Study on <i>Streptococcus mutans</i> and <i>Staphylococcus aureus</i>
title_sort incorporation of cbd into biodegradable dl lactide glycolide copolymers creates a persistent antibacterial environment an in vitro study on i streptococcus mutans i and i staphylococcus aureus i
topic cannabidiol
CBD
sustained-release device
PLGA scaffolds
antibacterial
antibiofilm
url https://www.mdpi.com/1999-4923/17/4/463
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