title: Preparation and Characterization of Three Tilmicosin-loaded Lipid Nanoparticles: Physicochemical Properties andin-vitroAntibacterial Activities.
abstract: Tilmicosin (TLM) is an important antibiotic in veterinary medicine with low bioavailability and safety. This study aimed to formulate and evaluate physicochemical properties, storage stability after lyophilization, and antibacterial activity of three TLM-loaded lipid nanoparticles (TLM-LNPs) including solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and lipid-core nanocapsules (LNCs). Physicochemical parameters such as particle size-mean diameter, polydispersity index, zeta potential, drug encapsulation efficiency (EE), loading capacity, and morphology of the formulations were evaluated and the effects of various cryoprotectants during lyophilization and storage for 8 weeks were also studied. The profiles of TLM release and the antibacterial activities of these TLM-LNPs suspensions (againstEscherichia coliandStaphylococcus aureus) were tested in comparison with their corresponding powders. TLM-LNPs suspensions were in nano-scale range with mean diameters of 186.3 ± 1.5, 149.6 ± 3.0, and 85.0 ± 1.0nm, and also EE, 69.1, 86.3, and 94.3% for TLM- SLNs, TLM-NLCs, and TLM- LNCs respectively. TLM-LNCs gave the best results with significantly low particle size and high EE (p<0.05). Mannitol was the most effective cryoprotectant for lyophilization and storage of TLM-LNPs. The drug release profiles were biphasic and the release times were longer at pH 7.4 where TLM-NLCs and TLM-LNCs powders showed longer release times. In microbiological tests,S. aureuswas about 4 times more sensitive thanE. colito TLM-LNPs with minimum inhibitory concentration ranges of 0.5-1.0 and 2-4 µg/mL respectively, and TLM-LNCs exhibited the best antibacterial activities. In conclusion, TLM-LNP formulations especially TLM-LNCs and TLM-NLCs are promising carriers for TLM with better drug encapsulation capacity, release behavior, and antibacterial activity.
authors.affiliation: Department of Pharmacology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
authors.forename: Alwan
authors.initials: A
authors.lastname: Al-Qushawi
authors.affiliation: Department of Pharmacology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Rassouli
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
authors.affiliation: Department of Avian Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
authors.forename: Seyed Mostafa
authors.initials: SM
authors.lastname: Peighambari
authors.affiliation: Nanotechnology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Esfandyari-Manesh
authors.affiliation: Department of Pharmacology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
authors.forename: Gholam Reza
authors.initials: GR
authors.lastname: Shams
authors.affiliation: Department of Avian Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
authors.forename: Azam
authors.initials: A
authors.lastname: Yazdani
keywords: Antibacterial activity; Lipid nanoparticles; Mannitol; Stability; Tilmicosin