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将大麻二酚掺入可生物降解的丙交酯/乙交酯共聚物中可营造持久抗菌环境:关于……的体外研究

The Incorporation of CBD into Biodegradable DL-Lactide/Glycolide Copolymers Creates a Persistent Antibacterial Environment: An In Vitro Study on and .

作者信息

Sionov Ronit Vogt, Siag Ahmad, Mersini Emma Theresa, Kogan Natalya M, Alkhazov Tatiana, Koman Igor, Rowlo Praveen, Gutkin Vitaly, Gross Menachem, Steinberg Doron

机构信息

Faculty of Dental Medicine, Institute of Biomedical and Oral Research (IBOR), The Hebrew University of Jerusalem, Ein Kerem Campus, Jerusalem 9112102, Israel.

Department of Otolaryngology-Head and Neck Surgery, Hadassah Medical Center, Jerusalem 9112102, Israel.

出版信息

Pharmaceutics. 2025 Apr 2;17(4):463. doi: 10.3390/pharmaceutics17040463.

Abstract

: Cannabidiol (CBD) is a natural compound from the L. plant, which has anti-inflammatory, anti-nociceptive, neuroprotective, and antibacterial activities. : 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 and for extended periods of time. : 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). : PURASORB 5010/CBD scaffolds had antibacterial activity against UA159, ATCC25923, and a clinical isolate of a multidrug-resistant (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. : 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.

摘要

大麻二酚(CBD)是一种从大麻植物中提取的天然化合物,具有抗炎、抗伤害感受、神经保护和抗菌活性。 本研究的目的是开发一种CBD缓释装置,该装置能够对革兰氏阳性菌提供抗菌作用并持续较长时间。 将CBD使用二甲基亚砜(DMSO)或丙酮作为溶剂掺入可生物降解的PURASORB 5010或PURASORB 7510丙交酯/乙交酯聚合物中,并且将干燥的聚合物支架每天暴露于新鲜的细菌培养物中。 每天通过光密度测定细菌生长,并使用MTT法测定生物膜的代谢活性。 通过高分辨率扫描电子显微镜(HR-SEM)观察聚合物支架上生物膜的形成。 通过酶联免疫吸附测定(ELISA)测量LPS刺激的RAW 264.7巨噬细胞释放的IL-6来确定其抗炎作用。 通过MTT法测定对正常Vero上皮细胞的细胞毒性。 通过气相色谱 - 质谱联用(GC-MS)测定CBD的每日释放量。 在长达17天的测试期内,PURASORB 5010/CBD支架对UA159、ATCC25923和一种多药耐药(MDRSA CI-M)菌株的临床分离株具有抗菌活性。PURASORB 7510/CBD支架也具有抗菌活性,但总体而言,随着时间的推移,其效果不如PURASORB 5010/CBD。向共聚物中添加聚乙二醇400(PEG400)可显著提高PURASORB 7510/CBD的抗菌活性,但对PURASORB 5010/CBD无效。聚合物支架中CBD的每日释放量足以减少LPS诱导的RAW 264.7巨噬细胞分泌IL-6,重要的是,它对RAW 264.7巨噬细胞或Vero上皮细胞均无细胞毒性。发现CBD的每日释放量在1.12至9.43μg/mL之间,远低于25μg/mL的细胞毒性剂量。 将CBD掺入可生物降解的PURASORB 5010中可用于制备具有抗菌和抗炎联合活性的医疗用途的缓释装置。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8307/12030335/965092ea4508/pharmaceutics-17-00463-g001.jpg

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