Abstract：
Efficient delivery of highly lipophilic drugs or prodrugs to the mesenteric lymph nodes (MLN) can be achieved following oral administration with lipids. However, it remains unclear which specific MLN can be targeted and to what extent. Moreover, the efficiency of drug delivery to the retroperitoneal lymph nodes (RPLN) has not been assessed. The aim of this study was to assess the distribution of a highly lipophilic model drug cannabidiol (CBD), known to undergo intestinal lymphatic transport following administration with lipids, into specific MLN and RPLN in rats at various time-points post dosing. In vivo studies showed that at 2 h following administration, significantly higher concentrations of CBD were present in the region second from the apex of the MLN chain. From 3 h following administration, concentrations in all MLN were similar. CBD was also found at substantial levels in RPLN. This study demonstrates that drug concentrations in specific MLN are different, at least at the peak of the absorption process. Moreover, in addition to the MLN, the RPLN may also be targeted by oral route of administration, which may have further implications for treatment of a range of diseases.
摘要：
在口服施用脂质后,可以实现高度亲脂性药物或前药向肠系膜淋巴结(MLN)的有效递送。然而,尚不清楚可以针对哪种特定的MLN以及在何种程度上。此外，药物递送至腹膜后淋巴结(RPLN)的效率尚未评估.这项研究的目的是评估高度亲脂性模型药物大麻二酚（CBD）的分布，已知在服用脂质后经历肠道淋巴运输，在给药后的不同时间点在大鼠中的特异性MLN和RPLN。体内研究表明，在给药后2小时，在MLN链顶端第二的区域中存在明显更高浓度的CBD。从给药后3小时开始，所有MLN中的浓度相似。在RPLN中也发现了大量的CBD。这项研究表明，特定MLN中的药物浓度是不同的，至少在吸收过程的峰值。此外，除了MLN,RPLN也可以通过口服给药途径靶向，这可能对一系列疾病的治疗有进一步的影响。
