Assessing Lymphatic Uptake of Lipids Using Magnetic Resonance Imaging: A Feasibility Study in Healthy Human Volunteers with Potential Application for Tracking Lymph Node Delivery of Drugs and Formulation Excipients.

Adelaide Jewell,Michael J Stocks,David Scurr,Hannah Williams,Marianne B Ashford,Caroline L Hoad,Snow Stolnik,James Butler,Pavel Gershkovich,Paul R Gellert,Penny A Gowland,Luca Marciani

doi:10.3390/pharmaceutics13091343

Abstract

Dietary lipids and some pharmaceutical lipid excipients can facilitate the targeted delivery of drugs to the intestinal lymphatics. Here, the feasibility of magnetic resonance imaging (MRI) for imaging lipid uptake into the intestinal lymphatics was assessed, shedding light on which lymph nodes can be targeted using this approach. Three healthy male volunteers were scanned at 3.0 T at baseline, 120, 180, 240, and 300 min post high-fat meal. A sagittal multi-slice image was acquired using a diffusion-weighted whole-body imaging sequence with background suppression (DWIBS) (pre inversion TI = 260 ms). Changes in area, major, and minor axis length were compared at each time point. Apparent diffusion coefficient (ADC) was calculated (b = 0 and 600 s/mm2) across eight slices. An average of 22 nodes could be visualised across all time points. ADC increased at 120 and 180 min compared to the baseline in all three participants by an average of 9.2% and 6.8%, respectively. In two participants, mean node area and major axis lengths increased at 120 and 180 min relative to the baseline. In conclusion, the method described shows potential for repeated lymph node measurements and the tracking of lipid uptake into the lymphatics. Further studies should focus on methodology optimisation in a larger cohort.

Highlights

Licensee MDPI, Basel, Switzerland.The intestinal lymphatic system is responsible for the absorption of dietary lipids from the small intestine in the form of large lipoproteins assembled in the enterocytes
Gastric volume and Small Bowel Water Content (SBWC) were measured at several time points following the high fat meal in order to understand when lipids may be entering the intestinal lymphatics for each individual
Data in the current study suggest that abdominal lymph node major and minor axes lengths may increase with the uptake of lipids

Summary

Introduction

The intestinal lymphatic system is responsible for the absorption of dietary lipids from the small intestine in the form of large lipoproteins assembled in the enterocytes (chylomicrons). Drugs with specific physiochemical properties including LogD7.4 > 5 have been shown to associate with chylomicrons. This means that they could avoid hepatic first-pass metabolism though delivery to mesenteric lymph nodes, bypassing the liver [1]. The use of lipid-based formulations to promote the formation of chylomicrons.

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