Pharmacokinetics and bioavailability of three promising tilmicosin-loaded lipid nanoparticles in comparison with tilmicosin phosphate following oral administration in broiler chickens

Authors: ALI RASSOULI, ALWAN AL-QUSHAWI, FATEMEH ATYABI, SEYED MOSTAFA PEIGHAMBARI, MEHDI ESFANDYARI-MANESH, GHOLAM REZA SHAMS

Abstract: Tilmicosin (TLM) is a semisynthetic antimicrobial agent used mainly in poultry and cattle, but it has relatively poor oral bioavailability. This study was conducted to compare the bioavailability (BA) and main pharmacokinetic (PK) parameters of TLM after oral administration of tilmicosin phosphate (TLM-PH) and three newly prepared lipid nanoparticles (LNPs) of TLM including solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and lipid-core nanocapsules (LNCs). Sixty broiler chickens were divided into eight groups. In four treatment groups (n = 10), each bird was given a single oral dose (20 mg/kg) of a TLM formulation after overnight fasting, and in four control groups (n = 5), the vehicles of those formulations or distilled water were given. Plasma TLM concentrations were analyzed using an HPLC method and the related PK parameters (C_max, T_max, AUC_0-$\infty$, t1/2, k_el, Cl_B/F, MRT, and V_d/F) were obtained by noncompartmental analysis. The relative bioavailability of TLM-SLNs, TLM-NLCs, and TLM-LNCs were 1.7, 2.7, and 3.6 times, respectively, more than the BA of TLM-PH. Mean C_max values were 1.21, 1.58, 1.76, and 2.17 µg/mL for TLM-PH, TLM-SLN, TLM-NLC, and TLM-LNC, respectively. In conclusion, TLM-LNPs improved drug BA and PK parameters, especially the TLM-LNC formulation, which suggests an efficient delivery system for TLM.

Keywords: Tilmicosin, lipid nanoparticles, pharmacokinetics, bioavailability, chicken

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