Multi-Compartment Pharmacokinetics and Tissue Bioavailability of Coenzyme Q10 from a Phospholipid-Based Self-Nanoemulsifying Drug Delivery System in Rats: A Distribution Pattern Consistent with a Possible Lymphatic Contribution

Objectives To evaluate a proprietary phospholipid-based self-nanoemulsifying CoQ10 delivery system using an integrated multi-compartment framework encompassing plasma pharmacokinetics, erythrocyte uptake, tissue distribution, and distribution-based indicators consistent with a possible contribution of intestinal lymphatic transport.Significance Current CoQ10 SNEDDS studies primarily assess plasma bioavailability, with limited evidence regarding intracellular delivery, tissue distribution, or absorption pathway modulation. This study extends evaluation beyond plasma-only metrics toward mechanistic, distribution-informed pharmacokinetics.Methods The formulation was characterised for droplet size, zeta potential, and drug loading after aqueous reconstitution. Cellular metabolic activity was assessed in Caco-2 cells using the MTT assay. In vivo pharmacokinetic and tissue-distribution studies were performed in Sprague–Dawley rats administered a single oral dose of crystalline CoQ10 or the phospholipid-based SNEDDS (30 mg/kg; n = 3/group) in this exploratory, hypothesis-generating study. Plasma, erythrocyte, and tissue CoQ10 concentrations were quantified by HPLC.Results The SNEDDS formed a stable nanoemulsion (104.2 ± 2 nm; PDI 0.221; zeta potential −52.1 mV). In Caco-2 cells, the formulation enhanced mitochondrial metabolic activity in a concentration-dependent manner. In vivo, the SNEDDS increased plasma Cmax 2.7-fold and AUC0-24 h 1.5-fold versus crystalline CoQ10 (relative bioavailability 149%). Erythrocyte CoQ10 concentrations and tissue deposition increased across all organs examined (1.3–4.5-fold). The liver-to-intestine concentration ratio inverted from 1.51 to 1.02, consistent with a possible contribution of intestinal lymphatic transport. Disproportionate Cmax enhancement relative to AUC indicated rate-limited absorption bypass.Conclusion The formulation enhanced systemic, cellular, and tissue-level CoQ10 delivery, supporting mechanistic evaluation beyond plasma bioavailability alone. The observed tissue distribution pattern is consistent with a potential contribution of intestinal lymphatic transport, although direct confirmation requires dedicated lymphatic transport studies.