Tier 4 — mechanistic

Enhancement of in vitro transcellular absorption and in vivo oral bioavailability of apigenin by self-nanoemulsifying drug delivery systems

Vilasinee Hirunpanich Sato, Hitoshi Sato, Manaw Sangfuang, Jannarin Nontakham, Varaporn Buraphacheep Junyaprasert, Veerawat Teeranachaideekul, Boontida Morakul
Scientific Reports 2024 14:32148

Bibliography

PubMed
PMID 39738511
PubMed Central
PMC11685950
DOI
10.1038/s41598-024-84063-2
Funding
Supported by the Mahidol University MU Strategic Research Fund 2023 (MU-SRF-RS-09A/66).
Competing interests
The authors declared no competing interests.

Study snapshot

DesignFormulation/stability study with in vitro Caco-2 transport, in vivo rat pharmacokinetics and OECD 425 acute oral toxicity testing
ModelCaco-2 intestinal epithelial monolayers; rats for pharmacokinetics; female ICR mice for acute oral toxicity
SampleCaco-2 assays plus rat pharmacokinetic cohorts; the OECD 425 limit test used a maximum of 5 non-pregnant female ICR mice at 2,000 mg/kg.
InterventionApigenin-loaded SNEDDS GTP2575 and GTP3070 versus apigenin coarse powder; oral apigenin dose 50 mg/kg in the rat PK comparison.
DurationSix-month formulation stability testing; 24-hour pharmacokinetic sampling; 14-day acute-toxicity observation.
EndpointsCaco-2 apparent permeability; Cmax and Tmax; AUC0-24 and AUC0-infinity; Relative oral bioavailability; Formulation stability; Acute oral toxicity

What the study showed, in plain terms

This preclinical study tested whether a self-nanoemulsifying formulation could solve apigenin's poor oral delivery. Two SNEDDS formulations increased movement across Caco-2 cell layers and substantially increased apigenin exposure in rats compared with coarse apigenin powder. The work is useful for formulation science, but it does not show that a nanoemulsified apigenin supplement produces better clinical outcomes in humans.

Key findings

GTP2575 and GTP3070 increased Caco-2 transcellular permeability. In rats, Cmax and AUC were higher than with coarse apigenin powder, with relative oral bioavailability about 3.8-fold and 3.3-fold higher, respectively. The formulations remained physicochemically stable for six months, and the acute oral toxicity limit test found no mortality at 2,000 mg/kg.

What this study can and cannot tell us

The pharmacokinetic and toxicity findings are preclinical and cannot establish human absorption, long-term safety, dosing equivalence or clinical benefit. The study tested specific excipient combinations, so the exposure gains should not be generalized to unrelated apigenin formulations.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology