Limits...
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.

Show MeSH

Related in: MedlinePlus

In vitro release of different tilmicosin formulations (mean ± standard deviation; n=3).Abbreviations: NaCl, sodium chloride; 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; HCl, hydrogen chloride; n, number; TMS, native tilmicosin.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4043706&req=5

f2-ijn-9-2655: In vitro release of different tilmicosin formulations (mean ± standard deviation; n=3).Abbreviations: NaCl, sodium chloride; 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; HCl, hydrogen chloride; n, number; TMS, native tilmicosin.

Mentions: The in vitro release profile of the TMS-HCO-NP suspensions compared to native tilmicosin is summarized as the cumulative percentage release of tilmicosin (Figure 2). The three TMS-HCO-NP suspensions displayed similar release patterns to that of freeze-dried TMS-HCO-NP powders. Drug release was rapid during the first 2 hours, followed by a relatively slower release phase lasting for 24 hours, after which a more gradual slow release was observed. Notably, the suspensions showed much faster initial release than the powders, and suspensions with smaller-sized particles showed faster initial release. During the first 2 hours in the NaCl solution (0.9% w/v), the cumulative releases of the three nanoparticle suspensions (particle sizes 900 nm, 450 nm and 150 nm) were 13.38%±1.50%, 24.04%±1.89%, and 29.35%±3.64%, respectively, compared to 2.80%±0.74%, 7.87%±0.34% and 14.37%±0.56% for the freeze-dried powders. The native tilmicosin control exhibited a rapid release with 45.65%±2.65% of drug released in 2 hours, and the release was almost complete (93.26%±0.48%) after 12 hours. Release studies in 0.1 M HCl showed similar trends to those in the NaCl solution, but the overall release was faster (Figure 2).


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 release of different tilmicosin formulations (mean ± standard deviation; n=3).Abbreviations: NaCl, sodium chloride; 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; HCl, hydrogen chloride; n, number; TMS, native tilmicosin.
© Copyright Policy
Related In: Results  -  Collection

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

f2-ijn-9-2655: In vitro release of different tilmicosin formulations (mean ± standard deviation; n=3).Abbreviations: NaCl, sodium chloride; 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; HCl, hydrogen chloride; n, number; TMS, native tilmicosin.
Mentions: The in vitro release profile of the TMS-HCO-NP suspensions compared to native tilmicosin is summarized as the cumulative percentage release of tilmicosin (Figure 2). The three TMS-HCO-NP suspensions displayed similar release patterns to that of freeze-dried TMS-HCO-NP powders. Drug release was rapid during the first 2 hours, followed by a relatively slower release phase lasting for 24 hours, after which a more gradual slow release was observed. Notably, the suspensions showed much faster initial release than the powders, and suspensions with smaller-sized particles showed faster initial release. During the first 2 hours in the NaCl solution (0.9% w/v), the cumulative releases of the three nanoparticle suspensions (particle sizes 900 nm, 450 nm and 150 nm) were 13.38%±1.50%, 24.04%±1.89%, and 29.35%±3.64%, respectively, compared to 2.80%±0.74%, 7.87%±0.34% and 14.37%±0.56% for the freeze-dried powders. The native tilmicosin control exhibited a rapid release with 45.65%±2.65% of drug released in 2 hours, and the release was almost complete (93.26%±0.48%) after 12 hours. Release studies in 0.1 M HCl showed similar trends to those in the NaCl solution, but the overall release was faster (Figure 2).

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