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Preparation and evaluation of tilmicosin-loaded hydrogenated castor oil nanoparticle suspensions of different particle sizes

Authors Chen X, Wang T, Lu M, Zhu L, Wang Y, Zhou W

Received 8 December 2013

Accepted for publication 22 January 2014

Published 27 May 2014 Volume 2014:9(1) Pages 2655—2664

DOI https://doi.org/10.2147/IJN.S58898

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

Xiaojin Chen, Ting Wang, Mengmeng Lu, Luyan Zhu, Yan Wang, WenZhong Zhou

Department of Preventitive Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China

Abstract: Three tilmicosin-loaded hydrogenated castor oil nanoparticle (TMS-HCO-NP) suspensions of different particle sizes were prepared with different polyvinyl alcohol surfactant concentrations using a hot homogenization and ultrasonic technique. The in vitro release, in vitro antibacterial activity, mammalian cytotoxicity, acute toxicity in mice, and stability study were conducted to evaluate the characteristics of the suspensions. The in vitro tilmicosin release rate, antibacterial activity, mammalian cytotoxicity, acute toxicity in mice, and stability of the suspensions were evaluated. When prepared with polyvinyl alcohol concentrations of 0.2%, 1%, and 5%, the mean diameters of the nanoparticles in the three suspensions were 920±35 nm, 452±10 nm, and 151±4 nm, respectively. The three suspensions displayed biphasic release profiles similar to that of freeze-dried TMS-HCO-NP powders, with the exception of having a faster initial release. Moreover, suspensions of smaller-sized particles showed faster initial release, and lower minimum inhibitory concentrations and minimum bactericidal concentrations. Time-kill curves showed that within 12 hours, the suspension with the 151 nm particles had the most potent bactericidal activity, but later, the suspensions with larger-sized particles showed increased antibacterial activity. None of the three suspensions were cytotoxic at clinical dosage levels. At higher drug concentrations, all three suspensions showed similar concentration-dependent cytotoxicity. The suspension with the smallest-sized particle showed significantly more acute toxicity in mice, perhaps due to faster drug release. All three suspensions exhibited good stability at 4°C and at room temperature for at least 6 months. These results demonstrate that TMS-HCO-NP suspensions can be a promising formulation for tilmicosin, and that nanoparticle size can be an important consideration for formulation development.

Keywords: tilmicosin, solid lipid nanoparticle suspension, particle size, release rate, antibacterial activity, toxicity


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