Chain length affects pancreatic lipase activity and the extent and pH–time profile of triglyceride lipolysis

Benito-Gallo, Paloma; Franceschetto, Alessandro; Wong, Jonathan; Marlow, Maria; Zann, Vanessa; Scholes, Peter; Gershkovich, Pavel

doi:10.1016/j.ejpb.2015.04.027

Cited by 62 publications

(39 citation statements)

References 61 publications

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“…In general, colloidal structures formed from lipolysis of MCT diffuse across the enterocytes gaining access to the portal vein, while digestion products generated from LCT can be re‐esterified, incorporated into chylomicrons, and absorbed into the lymph vessels . Hence, when lymphatic transport is the main mechanism of drug absorption from enterocytes into the systemic circulation, the role of LCT in lipid formulation is to enhance lymphatic pathway to improve bioavailability.…”

Section: Resultsmentioning

confidence: 99%

Influence of lipid composition on the oral bioavailability of cinnarizine sub‐microemulsions

Yin-rong

Wei

et al. 2016

Euro J Lipid Sci & Tech

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The oral bioavailability of cinnarizine is usually limited by its poor solubility in the gastrointestinal tract. In this study, two kinds of cinnarizine sub‐microemulsions (SMEs) were prepared using medium (MCT) and long (LCT) chain triglycerides, respectively, and the effect of the lipid composition on the oral bioavailability of SMEs was investigated in terms of stability, in vitro lipolysis, in situ single‐pass intestinal perfusion, and in vivo pharmacokinetics. The SMEs increased cinnarizine stability in simulated gastrointestinal fluid and in vitro lipolysis products of LCT‐SMEs showed better cinnarizine solubilization capacity than that of MCT‐SMEs. In addition, the absorption rate (Ka) and the effective permeability coefficient (Peff) of LCT‐SMEs were significantly improved compared with MCT‐SMEs. The AUC0‐t value of LCT‐SMEs was 4132.6 ± 673.4 ng/mL · h, which was 1.94‐fold higher than that of the aqueous suspension. Moreover, the AUC0‐t value of LCT‐SMEs was also significantly greater than that of MCT‐SMEs (2490.7 ± 685.3 ng/mL · h), owing to the better drug solubilization capacity of the complex colloidal mixtures formed from digestion of LCT. Hence, LCT‐SMEs was successful in improving the oral bioavailability of cinnarizine and it was a superior drug vehicle for oral administration. Practical applications: Owing to poor solubility of cinnarizine in the gastrointestinal tract, its commercially available dosage forms including tablets and capsules exhibit low oral bioavailability. Here we propose SMEs to improve oral bioavailability of cinnarizine. In addition, the influence of lipid composition on the oral absorption of SMEs was investigated, and LCT‐SMEs significantly increased the oral bioavailability of cinnarizine compared with MCT‐SMEs. So, in this study we show that LCT‐SMEs is a promising drug vehicle for oral administration of cinnarizine. The colloidal structures generated from digested long chain triglycerides (LCT) have a better cinnarizine solubilisation ability than that generated from medium chain triglycerides (MCT) digestion, resulting in increased oral absorption for the LCT formulation compared with MCT.

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Section: Resultsmentioning

confidence: 99%

Influence of lipid composition on the oral bioavailability of cinnarizine sub‐microemulsions

Yin-rong

Wei

et al. 2016

Euro J Lipid Sci & Tech

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“…The molecular mechanism by which lipolysis is increased is not known. It would be interesting to see whether dietary restriction changes the length or saturation level of stored TAGs, as this has been shown in other systems to alter the lipolysis rates (Benito-Gallo et al, 2015). In addition to increased TAG turnover, animals fed a restricted diet also demonstrate increased physical activity and improved muscle function (Katewa et al, 2012).…”

Section: The Role Of Muscle In Maintaining Lipid Homeostasismentioning

confidence: 99%

The Role of Muscle in Insect Energy Homeostasis

Bretscher

O’Connor

2020

Front. Physiol.

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Maintaining energy homeostasis is critical for ensuring proper growth and maximizing survival potential of all organisms. Here we review the role of somatic muscle in regulating energy homeostasis in insects. The muscle is not only a large consumer of energy, it also plays a crucial role in regulating metabolic signaling pathways and energy stores of the organism. We examine the metabolic pathways required to supply the muscle with energy, as well as muscle-derived signals that regulate metabolic energy homeostasis.

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“…This is because the long-chain triglycerides have a slower lipolysis rate than the medium-chain diester, which aligns with the results of previous studies. [27][28][29] Maisine 35-1 and Peceol consumed less NaOH than Labrafac PG due to the fewer ester bonds. Interestingly, the isopropyl ester of the monoester, IP, did not consume NaOH and was not digested ( Figure 1A).…”

Section: Ral-nne Developmentmentioning

confidence: 99%

<p>A Non-Lipolysis Nanoemulsion Improved Oral Bioavailability by Reducing the First-Pass Metabolism of Raloxifene, and Related Absorption Mechanisms Being Studied</p>

Ye¹,

Chen²,

Huang³

et al. 2020

IJN

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A non-lipolysis nanoemulsion (NNE) was designed to reduce the first-pass metabolism of raloxifene (RAL) by intestinal UDP-glucuronosyltransferases (UGTs) for increasing the oral absorption of RAL, coupled with in vitro and in vivo studies. Methods: In vitro stability of NNE was evaluated by lipolysis and the UGT metabolism system. The oral bioavailability of NNE was studied in rats and pigs. Finally, the absorption mechanisms of NNE were investigated by in situ single-pass intestinal perfusion (SPIP) in rats, Madin-Darby canine kidney (MDCK) cells model, and lymphatic blocking model. Results: The pre-NNE consisted of isopropyl palmitate, linoleic acid, Cremophor RH40, and ethanol in a weight ratio of 3.33:1.67:3:2. Compared to lipolysis nanoemulsion of RAL (RAL-LNE), the RAL-NNE was more stable in in vitro gastrointestinal buffers, lipolysis, and UGT metabolism system (p < 0.05). The oral bioavailability was significantly improved by the NNE (203.30%) and the LNE (205.89%) relative to the suspension group in rats. However, 541.28% relative bioavailability was achieved in pigs after oral NNE intake compared to the suspension and had twofold greater bioavailability than the LNE (p < 0.05). The RAL-NNE was mainly absorbed in the jejunum and had high permeability at the intestine of rats. The results of both SPIP and MDCK cell models demonstrated that the RAL-NNE was absorbed via endocytosis mediated by caveolin and clathrin. The other absorption route, the lymphatic transport (cycloheximide as blocking agent), was significantly improved by the NNE compared with the LNE (p < 0.05). Conclusion: A NNE was successfully developed to reduce the first-pass metabolism of RAL in the intestine and enhance its lymphatic transport, thereby improving the oral bioavailability. Altogether, NNE is a promising carrier for the oral delivery of drugs with significant first-pass metabolism.

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Chain length affects pancreatic lipase activity and the extent and pH–time profile of triglyceride lipolysis

Cited by 62 publications

References 61 publications

Influence of lipid composition on the oral bioavailability of cinnarizine sub‐microemulsions

Influence of lipid composition on the oral bioavailability of cinnarizine sub‐microemulsions

The Role of Muscle in Insect Energy Homeostasis

<p>A Non-Lipolysis Nanoemulsion Improved Oral Bioavailability by Reducing the First-Pass Metabolism of Raloxifene, and Related Absorption Mechanisms Being Studied</p>

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