Purpose: Reducing the first-pass hepatic effect via intestinal lymphatic transport is an effective way to increase the oral absorption of drugs. 2-Monoacylglycerol (2-MAG) as a primary digestive product of dietary lipids triglyceride, can be assembled in chylomicrons and then transported from the intestine into the lymphatic system. Herein, we propose a biomimetic strategy and report a 2-MAG mimetic nanocarrier to target the intestinal lymphatic system via the lipid absorption pathway and improve oral bioavailability. Methods: The 2-MAG mimetic liposomes were designed by covalently bonding serinol (SER) on the surface of liposomes named SER-LPs to simulate the structure of 2-MAG. Dihydroartemisinin (DHA) was chosen as the model drug because of its disadvantages such as poor solubility and high first-pass effect. The endocytosis and exocytosis mechanisms were investigated in Caco-2 cells and Caco-2 cell monolayers. The capacity of intestinal lymphatic transport was evaluated by ex vivo biodistribution and in vivo pharmacokinetic experiments. Results: DHA loaded SER-LPs (SER-LPs-DHA) had a particle size of 70 nm and a desirable entrapment efficiency of 93%. SER-LPs showed sustained release for DHA in the simulated gastrointestinal environment. In vitro cell studies demonstrated that the cellular uptake of SER-LPs primarily relied on the caveolae- rather than clathrin-mediated endocytosis pathway and preferred to integrate into the chylomicron assembly process through the endoplasmic reticulum/Golgi apparatus route. After oral administration, SER-LPs efficiently promoted drug accumulation in mesenteric lymphatic nodes. The oral bioavailability of DHA from SER-LPs was 10.40-fold and 1.17-fold larger than that of free DHA and unmodified liposomes at the same dose, respectively. Conclusion: SER-LPs improved oral bioavailability through efficient intestinal lymphatic transport. These findings of the current study provide a good alternative strategy for oral delivery of drugs with high first-pass hepatic metabolism.

An ultrahigh-performance liquid chromatography–tandem mass spectrometry method was developed and validated for the simultaneous determination of sterigmatocystin, verruculogen, enniatin A, fusarenon-X, fumonisins B1, B2, B3, aflatoxins B1, B2, G1, G2, ochratoxin A, deoxynivalenol, 3-acetyldeoxynivalenol, 5-acetyldeoxynivalenol, and zearalenone. The mycotoxins were extracted and cleaned up using a multitoxin column, separated on a C18 column, and then detected on a triple-quadrupole mass spectrometer. The limits of detection and quantification ranged within 0.2–2 µg/kg and 1–10 µg/kg, respectively. The recoveries ranged from 70.8 to 118.4%, with relative standard deviations below 15%. The method was used to analyze 80 samples obtained from Shandong Province in China. Fifty-eight samples were contaminated with 10 mycotoxins at concentrations ranging from 1.4 to 6566.1 µg/kg. Some samples exceeded the maximum limits in China and in European regulations for mycotoxins in unprocessed maize.

It is urgent to develop new antimalarial drugs with good therapeutic effects to address the emergence of drug resistance. Here, the artelinic acid-choline derivative (AD) was synthesized by dehydration reaction and esterification reaction, aimed to avoid the emergence of drug resistance by synergistic effect of artemisinins and choline derivative, which could compete with choline for rate-limiting enzymes in the phosphatidylcholine (PC) biosynthetic pathway. AD was formulated into liposomes (ADLs) by the thin-film hydration method. Efficacy of ADLs was evaluated by Peters 4-day suppression test. The suppression percentage againstPlasmodium yoeliiBY265 (PyBY265) in ADLs group was higher than those of positive control groups (dihydroartemisinin liposomes,P< 0.05) and other control groups (P⩽ 0.05) at the doses of 4.4, 8.8, 17.6µmol (kg·d)⁻¹, respectively. The negative conversion fraction, recrudescence fraction and survival fraction of ADLs group were superior to other control groups. Pharmacokinetics in rats after intravenous injection suggested that ADLs exhibited higher exposure levels (indexed by area under concentration-time curve) than that of AD solution, artelinic acid liposomes or artelinic acid solution (P< 0.01). Taken together, ADLs exhibited promising antimalarial efficacy and pharmacokinetic characteristics.