Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Complutense University, Madrid, Spain.
PLoS One. 2013;8(1):e54795. doi: 10.1371/journal.pone.0054795. Epub 2013 Jan 22.
Cannabinoids, the active components of marijuana and their derivatives, are currently investigated due to their potential therapeutic application for the management of many different diseases, including cancer. Specifically, Δ(9)-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) - the two major ingredients of marijuana - have been shown to inhibit tumor growth in a number of animal models of cancer, including glioma. Although there are several pharmaceutical preparations that permit the oral administration of THC or its analogue nabilone or the oromucosal delivery of a THC- and CBD-enriched cannabis extract, the systemic administration of cannabinoids has several limitations in part derived from the high lipophilicity exhibited by these compounds. In this work we analyzed CBD- and THC-loaded poly-ε-caprolactone microparticles as an alternative delivery system for long-term cannabinoid administration in a murine xenograft model of glioma. In vitro characterization of THC- and CBD-loaded microparticles showed that this method of microencapsulation facilitates a sustained release of the two cannabinoids for several days. Local administration of THC-, CBD- or a mixture (1:1 w:w) of THC- and CBD-loaded microparticles every 5 days to mice bearing glioma xenografts reduced tumour growth with the same efficacy than a daily local administration of the equivalent amount of those cannabinoids in solution. Moreover, treatment with cannabinoid-loaded microparticles enhanced apoptosis and decreased cell proliferation and angiogenesis in these tumours. Our findings support that THC- and CBD-loaded microparticles could be used as an alternative method of cannabinoid delivery in anticancer therapies.
大麻的有效成分大麻素及其衍生物，由于它们可能具有治疗多种疾病（包括癌症）的应用潜力，目前正在被研究。具体来说，Δ(9)-四氢大麻酚（THC）和大麻二酚（CBD）——大麻的两种主要成分——已被证明可以抑制许多癌症动物模型中的肿瘤生长，包括神经胶质瘤。尽管有几种药物制剂可以口服给予 THC 或其类似物纳布啡，或经口给予富含 THC 和 CBD 的大麻提取物，但由于这些化合物具有较高的亲脂性，因此全身给予大麻素存在一些限制。在这项工作中，我们分析了负载 CBD 和 THC 的聚己内酯微球作为一种替代的长期大麻素给药系统，用于神经胶质瘤的小鼠异种移植模型。体外 THC 和 CBD 负载微球的表征表明，这种微囊化方法有利于两种大麻素在数天内持续释放。将 THC、CBD 或 THC 和 CBD 负载微球的混合物（1:1 w:w）每 5 天局部给药一次，可降低携带神经胶质瘤异种移植物的小鼠的肿瘤生长速度，其效果与每日局部给予相同剂量的那些大麻素溶液相同。此外，用负载大麻素的微球治疗可增强这些肿瘤中的细胞凋亡，并减少细胞增殖和血管生成。我们的研究结果支持将 THC 和 CBD 负载微球用作癌症治疗中替代大麻素给药的方法。
