Solid Lipid Nanoparticles for Duodenum Targeted Oral Delivery of Tilmicosin
Kaixiang Zhou,
Yuanyuan Yan,
Dongmei Chen,
Lingli Huang,
Chao Li,
Kuiyu Meng,
Shuge Wang,
Samah Attia Algharib,
Zonghui Yuan,
Shuyu Xie
Affiliations
Kaixiang Zhou
National Reference Laboratory of Veterinary Drug Residues (H.Z.A.U.) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Wuhan 430070, China
Yuanyuan Yan
National Reference Laboratory of Veterinary Drug Residues (H.Z.A.U.) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Wuhan 430070, China
Dongmei Chen
MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan 430070, China
Lingli Huang
MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan 430070, China
Chao Li
National Reference Laboratory of Veterinary Drug Residues (H.Z.A.U.) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Wuhan 430070, China
Kuiyu Meng
National Reference Laboratory of Veterinary Drug Residues (H.Z.A.U.) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Wuhan 430070, China
Shuge Wang
National Reference Laboratory of Veterinary Drug Residues (H.Z.A.U.) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Wuhan 430070, China
Samah Attia Algharib
National Reference Laboratory of Veterinary Drug Residues (H.Z.A.U.) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Wuhan 430070, China
Zonghui Yuan
MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan 430070, China
Shuyu Xie
MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan 430070, China
Developing a targeted oral delivery system to improve the efficacy of veterinary antibiotics and reduce their consumption and environmental risks is urgent. To achieve the duodenum-targeted release of tilmicosin, the enteric granule containing tilmicosin-loaded solid lipid nanoparticles (TIL-SLNs) was prepared based on its absorption site and transport characteristics. The in vitro release, release mechanisms, stability, palatability, and pharmacokinetics of the optimum enteric granules were studied. The intestine perfusion indicated that the main absorption site of tilmicosin was shifted to duodenum from ileum by TIL-SLNs, while, the absorption of TIL-SLNs in the duodenum was hindered by P-glycoprotein (P-gp). In contrast with TIL-SLNs, the TIL-SLNs could be more effectively delivered to the duodenum in intact form after enteric coating. Its effective permeability coefficient was enhanced when P-gp inhibitors were added. Compared to commercial premix, although the TIL-SLNs did not improve the oral absorption of tilmicosin, the time to reach peak concentration (Tmax) was obviously shortened. After the enteric coating of the granules containing SLNs and P-gp inhibitor of polysorbate-80, the oral absorption of tilmicosin was improved 2.72 fold, and the Tmax was shortened by 2 h. The combination of duodenum-targeted release and P-gp inhibitors was an effective method to improve the oral absorption of tilmicosin.
