Cannabidiol bioavailability after nasal and transdermal application: effect of permeation enhancers
Cannabidiol bioavailability after nasal and transdermal application: effect of permeation enhancers
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DOI：
10.3109/03639041003657295
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发表时间：
2010-09-01
影响因子：
3.4
通讯作者：
Stinchcomb, Audra L.
中科院分区：
文献类型：
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作者：
Paudel, Kalpana S.;Hammell, Dana C.;Stinchcomb, Audra L.
内容：非精神活性大麻素，大麻二酚（CBD），具有治疗慢性和“突破性”疼痛的巨大潜力，这种疼痛可能发生在某些情况下，如癌症。为了实现这一目标，需要为CBD开发合适的非侵入性药物递送系统。慢性疼痛缓解可以通过透皮途径最好地实现，而“突破性”疼痛可以通过鼻内（IN）递送最好地缓解。结合IN和CBD的经皮给药可能有助于以非成瘾性非阿片类药物治疗的形式提供患者需求驱动的治疗。目的：在此我们评价了CBD在有和没有渗透促进剂的情况下的IN和经皮给药。材料和方法：分别在大鼠和豚鼠体内进行了鼻腔和经皮渗透研究。结果：CBD在10分钟内被鼻内吸收，生物利用度为34- 46%，除了100%聚乙二醇制剂在大鼠中。生物利用度没有改善与增强剂。经皮凝胶应用后，豚鼠中CBD的稳态血浆浓度为6.3 +/- 2.1 ng/mL，在15.5 +/- 11.7小时达到。达到显著的稳态血浆浓度表明CBD通过这种给药途径可用于慢性疼痛治疗。在增强剂存在下，稳态浓度增加了3.7倍。透皮研究存在良好的体外和体内相关性。结论：CBD可通过经皮和经皮给药途径给药。
Context: The nonpsychoactive cannabinoid, cannabidiol (CBD), has great potential for the treatment of chronic and 'breakthrough' pain that may occur in certain conditions like cancer. To fulfill this goal, suitable noninvasive drug delivery systems need to be developed for CBD. Chronic pain relief can be best achieved through the transdermal route, whereas 'breakthrough' pain can be best alleviated with intranasal (IN) delivery. Combining IN and transdermal delivery for CBD may serve to provide patient needs-driven treatment in the form of a nonaddictive nonopioid therapy. Objective: Herein we have evaluated the IN and transdermal delivery of CBD with and without permeation enhancers. Materials and Methods: In vivo studies in rats and guinea pigs were carried out to assess nasal and transdermal permeation, respectively. Results: CBD was absorbed intranasally within 10 minutes with a bioavailability of 34-46%, except with 100% polyethylene glycol formulation in rats. Bioavailability did not improve with enhancers. The steady-state plasma concentration of CBD in guinea pigs after transdermal gel application was 6.3 +/- 2.1 ng/mL, which was attained at 15.5 +/- 11.7 hours. The achievement of a significant steady-state plasma concentration indicates that CBD is useful for chronic pain treatment through this route of administration. The steady-state concentration increased by 3.7-fold in the presence of enhancer. A good in vitro and in vivo correlation existed for transdermal studies. Conclusion: The results of this study indicated that CBD could be successfully delivered through the IN and transdermal routes.