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

Chen X, Wang T, Lu M, Zhu L, Wang Y, Zhou W - Int J Nanomedicine (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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Cytotoxicity of TMS-HCO-NP suspensions on the BHK-21 cell line.Notes: Cell viability was assessed after 1 day of coculture. The viability of the cells that were not treated with TMS-HCO-NP was taken as 100%. Results are expressed as the mean ± standard deviation (n=5).Abbreviations: T0.2, tilmicosin-loaded hydrogenated castor oil nanoparticle suspension with a particle size of 900 nm; T1, tilmicosin-loaded hydrogenated castor oil nanoparticle suspension with a particle size of 450 nm; T5, tilmicosin-loaded hydrogenated castor oil nanoparticle suspension with a particle size of 150 nm; TMS, native tilmicosin; Control, cells that were not treated with tilmicosin-loaded hydrogenated castor oil nanoparticles; TMS-HCO-NP, tilmicosin-loaded hydrogenated castor oil nanoparticles; BHK-21, baby hamster kidney cell line; n, number.
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f4-ijn-9-2655: Cytotoxicity of TMS-HCO-NP suspensions on the BHK-21 cell line.Notes: Cell viability was assessed after 1 day of coculture. The viability of the cells that were not treated with TMS-HCO-NP was taken as 100%. Results are expressed as the mean ± standard deviation (n=5).Abbreviations: T0.2, tilmicosin-loaded hydrogenated castor oil nanoparticle suspension with a particle size of 900 nm; T1, tilmicosin-loaded hydrogenated castor oil nanoparticle suspension with a particle size of 450 nm; T5, tilmicosin-loaded hydrogenated castor oil nanoparticle suspension with a particle size of 150 nm; TMS, native tilmicosin; Control, cells that were not treated with tilmicosin-loaded hydrogenated castor oil nanoparticles; TMS-HCO-NP, tilmicosin-loaded hydrogenated castor oil nanoparticles; BHK-21, baby hamster kidney cell line; n, number.

Mentions: Mammalian cytotoxicity for the three drug-loaded nanoparticle suspensions was assessed with a BHK-21 cell line, with drug concentrations ranging from 32–512 μg/mL (Figure 4). None of the three suspensions showed cytotoxic activity at 32 μg/mL. Higher doses led to gradually increasing cytotoxicity, but no significant differences were observed among the different formulations. The tilmicosin control showed very low cytotoxicity.


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

Chen X, Wang T, Lu M, Zhu L, Wang Y, Zhou W - Int J Nanomedicine (2014)

Cytotoxicity of TMS-HCO-NP suspensions on the BHK-21 cell line.Notes: Cell viability was assessed after 1 day of coculture. The viability of the cells that were not treated with TMS-HCO-NP was taken as 100%. Results are expressed as the mean ± standard deviation (n=5).Abbreviations: T0.2, tilmicosin-loaded hydrogenated castor oil nanoparticle suspension with a particle size of 900 nm; T1, tilmicosin-loaded hydrogenated castor oil nanoparticle suspension with a particle size of 450 nm; T5, tilmicosin-loaded hydrogenated castor oil nanoparticle suspension with a particle size of 150 nm; TMS, native tilmicosin; Control, cells that were not treated with tilmicosin-loaded hydrogenated castor oil nanoparticles; TMS-HCO-NP, tilmicosin-loaded hydrogenated castor oil nanoparticles; BHK-21, baby hamster kidney cell line; n, number.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4043706&req=5

f4-ijn-9-2655: Cytotoxicity of TMS-HCO-NP suspensions on the BHK-21 cell line.Notes: Cell viability was assessed after 1 day of coculture. The viability of the cells that were not treated with TMS-HCO-NP was taken as 100%. Results are expressed as the mean ± standard deviation (n=5).Abbreviations: T0.2, tilmicosin-loaded hydrogenated castor oil nanoparticle suspension with a particle size of 900 nm; T1, tilmicosin-loaded hydrogenated castor oil nanoparticle suspension with a particle size of 450 nm; T5, tilmicosin-loaded hydrogenated castor oil nanoparticle suspension with a particle size of 150 nm; TMS, native tilmicosin; Control, cells that were not treated with tilmicosin-loaded hydrogenated castor oil nanoparticles; TMS-HCO-NP, tilmicosin-loaded hydrogenated castor oil nanoparticles; BHK-21, baby hamster kidney cell line; n, number.
Mentions: Mammalian cytotoxicity for the three drug-loaded nanoparticle suspensions was assessed with a BHK-21 cell line, with drug concentrations ranging from 32–512 μg/mL (Figure 4). None of the three suspensions showed cytotoxic activity at 32 μg/mL. Higher doses led to gradually increasing cytotoxicity, but no significant differences were observed among the different formulations. The tilmicosin control showed very low cytotoxicity.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

Show MeSH
Related in: MedlinePlus