Comparative pharmacokinetics and bioavailability of three promising tilmicosin-loaded lipid nanoparticles and conventional tilmicosin phosphate following oral administration in broiler chickens

Tilmicosin (TLM) is a semi-synthetic macrolide antibiotic used mainly for the treatment of poultry and cattle respiratory diseases, but it has problems with relatively poor oral bioavailability and dose-dependent toxicity. The present study aimed to compare bioavailability (BA) and the main pharmacokinetic (PK) parameters of TLM after oral application of a conventional tilmicosin phosphate solution (TLM-PH) and three newly prepared lipid nanoparticles (LNPs) as potential oral delivery systems; solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) and lipid-core nanocapsule (LNCs). Sixty healthy broiler chickens, aged 35 days, were divided into 8 groups. 4 treatment groups (10 birds each) given a single oral dose of different TLM formulations after an overnight fasting as well as 4 control groups (5 birds each) received vehicles of formulations or distilled water. Blood samples were taken before and up to 120 hours following drug administration. Plasma TLM concentrations were analyzed using an HPLC method and its PK parameters (Cmax, Tmax, AUC0–∞, t1/2, kel, ClB, MRT and Vd,) were obtained using non-compartmental analysis. The relative BA of TLM-SLNs, TLM-NLCs and TLM-LNCs were 166%, 271% and 361% when compared to TLM-PH, respectively. Cmax values were 1.21±0.09, 1.58±0.12, 1.76±0.38 and 2.17±0.3μg/ml for TLM-PH, TLM-SLN, TLM-NLC and TLM-LNC respectively. Tmax values were also 2.40±0.04, 5.60±0.17, 4.80±0.30 and 12.00±0.00 h, respectively. This investigation demonstrated the superiority of LNCs over other formulations by improving TLM absorption and prolonging its persistence in blood circulation. It was concluded that the LNPs improved BA and PK parameters of TLM especially LNCs formulation, so they could be regarded as promising therapeutic alternatives to TLM-PH.