Department of Polymers and Plastics Engineering, Shenkar College of Engineering, Design and Art, Ramat-Gan 52526, Israel.
The Laboratory of Cancer Biology and Cannabinoid Research, Department of Biology, Technion-Israel Institute of Technology, Haifa 320003, Israel.
ACS Appl Mater Interfaces. 2020 May 27;12(21):23707-23716. doi: 10.1021/acsami.0c04435. Epub 2020 May 15.
The therapeutic effect of the plant largely depends on the presence and specific ratio of a spectrum of phytocannabinoids. Although prescription of medicinal for various conditions constantly grows, its consumption is mostly limited to oral or respiratory pathways, impeding its duration of action, bioavailability, and efficacy. Herein, a long-acting formulation in the form of melt-printed polymeric microdepots for full-spectrum cannabidiol (CBD)-rich extract administration is described. When injected subcutaneously in mice, the microdepots facilitate sustained release of the encapsulated extract over a two-week period. The prolonged delivery results in elevated serum levels of multiple, major and minor, phytocannabinoids for over 14 days, compared to extract injection. A direct analysis of the microdepots retrieved from the injection site gives rise to an empirical model for the release kinetics of the phytocannabinoids as a function of their physical traits. As a proof of concept, we compare the long-term efficacy of a single administration of the microdepots to a single administration of extract in a pentylenetetrazol-induced convulsion model. One week following administration, the microdepots reduce the incidence of tonic-clonic seizures by 40%, increase the survival rate by 50%, and the latency to first tonic-clonic seizures by 170%. These results suggest that a long-term full-spectrum delivery system may provide new form of administration and treatments.
该植物的治疗效果在很大程度上取决于一系列植物大麻素的存在和特定比例。尽管各种条件下的药用 的处方不断增加，但它的使用主要限于口服或呼吸途径，从而阻碍了其作用持续时间、生物利用度和疗效。在此，我们描述了一种以全谱大麻二酚（CBD）丰富提取物为给药形式的熔融印刷聚合物微滴长效制剂。当将微滴皮下注射到小鼠中时，微滴能够在两周的时间内促进封装提取物的持续释放。与 提取物注射相比，这种延长的输送导致多种主要和次要植物大麻素的血清水平升高超过 14 天。从注射部位回收的微滴的直接分析产生了一个经验模型，用于根据植物大麻素的物理特性来描述它们的释放动力学。作为概念验证，我们将单次给予微滴与单次给予 提取物在戊四氮诱导的惊厥模型中的长期疗效进行了比较。给药后一周，微滴使强直性阵挛性发作的发生率降低了 40%，存活率提高了 50%，首次强直性阵挛性发作的潜伏期延长了 170%。这些结果表明，长期的全谱 输送系统可能为 提供新的给药和治疗形式。
