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.