Natural sesame oil is superior to pre-digested lipid formulations and purified triglycerides in promoting the intestinal lymphatic transport and systemic bioavailability of cannabidiol

Feng, Wanshan; Qin, Chaolong; Chu, Yen Ju; Berton, Mattia; Lee, Jong Bong; Zgair, Atheer; Bettonte, Sara; Stocks, Michael J.; Constantinescu, Cris S.; Barrett, David A.; Fischer, Peter M.; Gershkovich, Pavel

doi:10.1016/j.ejpb.2021.02.013

Cited by 28 publications

(19 citation statements)

References 44 publications

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“…In addition, in an attempt to enhance lipid uptake, the lipid content of the meal or formulation could be adjusted to include a higher lipid content. This may include ong-chain triglycerides, which have been shown in preclinical studies to enhance lymphatic uptake [ 33 ]. This, however, would require additional gastric emptying time data, which would likely be delayed as a result and may pose problems with palatability.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…All rats were sacrificed at 1.5 or 2.5 h post-administration in all groups. Blood, lymph fluid and mesenteric lymph nodes (MLN) were then harvested as described in our previous studies and stored at –80 °C until analysis [ 5 , 6 ]. In addition, after the completion of pharmacokinetic study at 12 h, animals were sacrificed, and MLN were collected for further analysis.…”

Section: Methodsmentioning

confidence: 99%

“…The sample preparation procedure was performed using a combination of protein precipitation and liquid–liquid extraction before injection into the HPLC system as previously described [ 5 ]. Briefly, fifty microliters of lipid phase, 100 μL of micelle phase and 100 μL sediment phase were used for sample preparation in a 16 × 100 mm glass tube.…”

Section: Methodsmentioning

confidence: 99%

“…The sample preparation method for plasma (or serum) and tissue samples was performed as previously described [ 5 , 39 ]. Briefly, MLNs were isolated from the surrounding fatty tissues, then homogenized in water in ratio of 1:3 ( w / v ).…”

Section: Methodsmentioning

confidence: 99%

“…A recent clinical study has also shown that sesame oil has increased CBD oral absorption eight-fold compared to CBD powder in healthy male volunteers [ 22 ]. However, both the intestinal lymphatic transport and systemic bioavailability of CBD administered in sesame oil vehicle were associated with substantial variability [ 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Inclusion of Medium-Chain Triglyceride in Lipid-Based Formulation of Cannabidiol Facilitates Micellar Solubilization In Vitro, but In Vivo Performance Remains Superior with Pure Sesame Oil Vehicle

et al. 2021

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Oral sesame oil-based formulation facilitates the delivery of poorly water-soluble drug cannabidiol (CBD) to the lymphatic system and blood circulation. However, this natural oil-based formulation also leads to considerable variability in absorption of CBD. In this work, the performance of lipid-based formulations with the addition of medium-chain triglyceride (MCT) or surfactants to the sesame oil vehicle has been tested in vitro and in vivo using CBD as a model drug. The in vitro lipolysis has shown that addition of the MCT leads to a higher distribution of CBD into the micellar phase. Further addition of surfactants to MCT-containing formulations did not improve distribution of the drug into the micellar phase. In vivo, formulations containing MCT led to lower or similar concentrations of CBD in serum, lymph and MLNs, but with reduced variability. MCT improves the emulsification and micellar solubilization of CBD, but surfactants did not facilitate further the rate and extent of lipolysis. Even though addition of MCT reduces the variability, the in vivo performance for the extent of both lymphatic transport and systemic bioavailability remains superior with a pure natural oil vehicle.

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Oral administration of tipranavir with long-chain triglyceride results in moderate intestinal lymph targeting but no efficient delivery to HIV-1 reservoir in mesenteric lymph nodes

Chu

Qin

Feng

et al. 2021

International Journal of Pharmaceutics

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Natural sesame oil is superior to pre-digested lipid formulations and purified triglycerides in promoting the intestinal lymphatic transport and systemic bioavailability of cannabidiol

Cited by 28 publications

References 44 publications

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

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

Inclusion of Medium-Chain Triglyceride in Lipid-Based Formulation of Cannabidiol Facilitates Micellar Solubilization In Vitro, but In Vivo Performance Remains Superior with Pure Sesame Oil Vehicle

Oral administration of tipranavir with long-chain triglyceride results in moderate intestinal lymph targeting but no efficient delivery to HIV-1 reservoir in mesenteric lymph nodes

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