Oxytetracycline delivery in rainbow trout (Oncorhynchus mykiss) using zinc-alginate microparticles: Formulation optimization, release kinetics, and relative bioavailability

Abstract

Antimicrobial use in salmonid aquaculture must be optimized to maintain therapeutic efficacy while limiting environmental impacts. This study evaluated zinc‑alginate microparticles (MP) as an oral delivery system for oxytetracycline (OTC) in rainbow trout, focusing on formulation optimization, release kinetics and relative bioavailability. Microparticles were produced in a single step by combined ionic gelation and atomization, using a fixed OTC load (1.19 g) and varying alginate concentrations (0.5, 1.0 and 2.0 g). The resulting MPs showed elongated, invaginated morphologies (8.1–13.6 µm), highly negative zeta potentials (−56 to −58 mV), production yields ≥ 57% and association efficiencies > 95%. OTC loading was inversely related to alginate content. In vitro release testing with USP apparatus 4 demonstrated that increasing alginate concentration markedly slowed drug release; the 2 g formulation (MP2‑OTC) released only about 20% of the encapsulated OTC over 72 h. Pharmacokinetic studies in rainbow trout ( Oncorhynchus mykiss ) showed that MP2‑OTC achieved a sustained‑release profile compared with a commercial OTC formulation, with a reduced C max (200.46 vs. 337.37 µg/mL), doubled T max (24 vs. 12 h), lower absorption and elimination rate constants (Ka and Ke 0.015 h⁻¹), and a 34% higher total drug exposure (AUC0–∞ 17 618 µg·h/mL). These results indicate that zinc‑alginate MPs can extend systemic OTC residence time and improve oral relative bioavailability in rainbow trout, supporting this platform as a promising strategy that may help enhance antimicrobial therapy and could potentially reduce dosing frequency and environmental loading in salmonid aquaculture.