聚乙烯醇水凝胶释放δ-9-四氢大麻酚及其与人类皮肤成纤维细胞的安全相互作用

Shujun Cui, Ze Zhang, Denis Rodrigue, François Béland, Mahmoud Rouabhia
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摘要

本研究旨在设计一种富含 THC 的水凝胶,用于局部输送大麻衍生物。我们使用聚乙烯醇 (PVA) 与丙二醇 (PG)、植物甘油 (VG) 或两者混合制成水凝胶,以促进δ-9-四氢大麻酚 (THC) 的溶解。水凝胶呈现棕色,证实了大麻素的存在。与单独的 PVA 相比,它们具有多孔结构和更好的机械性能。事实上,含有 PG、VG 或两者的水凝胶在含水量较低时表现出弹性变形行为。傅立叶变换红外分析表明,在 1,575 和 1,619 cm-1 处有两个特定的峰值,证实了水凝胶中含有 THC。在所有水凝胶表面培养人的真皮成纤维细胞证实了富含 THC 的水凝胶的安全性,因为细胞粘附性与对照组(不含 THC)相当。此外,粘附在水凝胶上的细胞可以增殖,在 48 小时和 72 小时后细胞存活率有所提高,富含 THC 的 PVA-PG-VG 水凝胶的细胞增殖率更高。超高效液相色谱法(UPLC)显示,在含有 PG 和 VG 或两者的水凝胶培养 24 小时后,培养基中出现了 203 至 290 微克的 THC。相比之下,PVA 水凝胶释放的四氢大麻酚更高,达到 852 微克。值得注意的是,与单独使用 PVA 相比,含有 PG、VG 或两者的水凝胶在 24、48 和 72 小时的 THC 释放速度较慢。总之,本研究设计了一种安全的富含 THC 的 PVA-PG-VG 水凝胶,作为局部使用大麻素控制组织疾病(如炎症)的功能性输送系统。
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Release of delta-9-tetrahydrocannabinol from polyvinyl alcohol hydrogels and its safe interaction with human skin fibroblasts
This study aimed to design a THC-rich hydrogel to deliver cannabis derivatives topically. We developed hydrogels using polyvinyl alcohol (PVA) mixed with propylene glycol (PG), vegetable glycerin (VG), or both to facilitate the dissolution of delta-9-tetrahydrocannabinol (THC). The hydrogels showed a brown color, confirming the presence of the cannabinoid. They exhibit a porous structure and better mechanical properties than PVA alone. Indeed, the hydrogel containing PG, VG, or both showed elastic deformation behaviors with lower water content. FTIR analysis demonstrated the presence of THC with two specific peaks at 1,575 and 1,619 cm−1, confirming the presence of THC in the hydrogels. Human dermal fibroblast cultures onto the surface of all hydrogels confirmed the safety of the THC-rich hydrogel as the cell adhesion was comparable to the control (no THC). Furthermore, cells adhering to the hydrogels could proliferate, showing increased cell viability at 48 and 72 h, with a higher proliferation obtained with the THC-rich PVA-PG-VG hydrogels. Such cell behavior could be due to the release of the THC in the culture medium, as demonstrated by ultra-high performance liquid chromatography (UPLC), showing the presence of THC in the culture medium, ranging from 203 to 290 μg after 24 h of incubation of the hydrogels containing PG and VG or both. In comparison, the released THC from the PVA hydrogel was higher, reaching 852 μg. It is interesting to note that the THC release at 24, 48, and 72 h was slower with the hydrogels containing PG, VG, and both, compared to PVA alone. Overall, the present study has designed safe THC-rich PVA-PG-VG hydrogels as a functional delivery system for the topical use of cannabinoids to control tissue diseases, such as inflammation.
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