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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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In vitro time-kill curve (mean ± standard deviation; n=3).Abbreviations: cfu, colony-forming units; 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; MHB, Mueller–Hinton broth.
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f3-ijn-9-2655: In vitro time-kill curve (mean ± standard deviation; n=3).Abbreviations: cfu, colony-forming units; 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; MHB, Mueller–Hinton broth.

Mentions: Next, the time-kill curves for the three TMS-HCO-NP suspensions and native tilmicosin were compared (Figure 3). Within the first 12 hours, suspensions of the smallest nanoparticles had the most potent antibacterial activity. The number of bacteria colonies in the cultures with the three suspensions increased from an initial density of 5.0×105 cfu/mL to densities of 4.0×106 cfu/mL, 4.5×107 cfu/mL, and 1.4×108 cfu/mL at 12 hours (particle size ranging from small to large) and 7.3×106 cfu/mL in the culture with the native drug. From 12–24 hours, the culture with the smallest-sized particle grew more rapidly, as it showed a fast cfu increase (from 4.0×106 cfu/mL to 1.2×108 cfu/mL) with a rate comparable to the growth of the culture with native tilmicosin (from 7.3×106 cfu/mL to 1.5×108 cfu/mL), whereas cultures with the other two suspensions grew more slowly (from 4.5×107 cfu/mL to 1.9×108 cfu/mL for 450 nm-sized particle and 1.4×108 cfu/mL to 2.7×108 cfu/mL for 900 nm-sized particle, respectively). Bacterial densities for all cultures increased slowly between 24–36 hours with no significant differences observed among the formulations.


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)

In vitro time-kill curve (mean ± standard deviation; n=3).Abbreviations: cfu, colony-forming units; 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; MHB, Mueller–Hinton broth.
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Related In: Results  -  Collection

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

f3-ijn-9-2655: In vitro time-kill curve (mean ± standard deviation; n=3).Abbreviations: cfu, colony-forming units; 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; MHB, Mueller–Hinton broth.
Mentions: Next, the time-kill curves for the three TMS-HCO-NP suspensions and native tilmicosin were compared (Figure 3). Within the first 12 hours, suspensions of the smallest nanoparticles had the most potent antibacterial activity. The number of bacteria colonies in the cultures with the three suspensions increased from an initial density of 5.0×105 cfu/mL to densities of 4.0×106 cfu/mL, 4.5×107 cfu/mL, and 1.4×108 cfu/mL at 12 hours (particle size ranging from small to large) and 7.3×106 cfu/mL in the culture with the native drug. From 12–24 hours, the culture with the smallest-sized particle grew more rapidly, as it showed a fast cfu increase (from 4.0×106 cfu/mL to 1.2×108 cfu/mL) with a rate comparable to the growth of the culture with native tilmicosin (from 7.3×106 cfu/mL to 1.5×108 cfu/mL), whereas cultures with the other two suspensions grew more slowly (from 4.5×107 cfu/mL to 1.9×108 cfu/mL for 450 nm-sized particle and 1.4×108 cfu/mL to 2.7×108 cfu/mL for 900 nm-sized particle, respectively). Bacterial densities for all cultures increased slowly between 24–36 hours with no significant differences observed among the formulations.

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