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Title

Preparation and Characterization of Three Tilmicosin-loaded Lipid Nanoparticles: Physicochemical Properties and in-vitro Antibacterial Activities

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 Start Page 663 | End Page 676

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 (against Escherichia coli and Staphylococcus 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. aureus was about 4 times more sensitive than E. coli to TLM-LNPs with minimum inhibitory concentration ranges of 0. 5-1. 0 and 2-4 μ g/mL respectively, and TLM-LNCs exhibited the best antibacterial activities. In conclusion, TLMLNP formulations especially TLM-LNCs and TLM-NLCs are promising carriers for TLM with better drug encapsulation capacity, release behavior, and Antibacterial activity.

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