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The fate of calcium carbonate nanoparticles administered by oral route: absorption and their interaction with biological matrices.

Lee JA, Kim MK, Kim HM, Lee JK, Jeong J, Kim YR, Oh JM, Choi SJ - Int J Nanomedicine (2015)

Bottom Line: N-Cal interacted more with biomatrices than bulk materials in vitro and ex vivo, as evidenced by high fluorescence quenching ratios, but it did not interact more actively with biomatrices in vivo.A biokinetic study revealed that orally delivered N-Cal was more rapidly absorbed into the blood stream than B-Cal, but no significant differences were observed between the two in terms of absorption efficiencies or tissue distributions.We conclude that calcium carbonate nanoparticles can act more actively with biological matrices in vitro and ex vivo, but that in vivo, their biological interactions and biokinetics are not affected by particle size.

View Article: PubMed Central - PubMed

Affiliation: Department of Food Science and Technology, Seoul Women's University, Seoul, Republic of Korea.

ABSTRACT

Background: Orally administered particles rapidly interact with biological fluids containing proteins, enzymes, electrolytes, and other biomolecules to eventually form particles covered by a corona, and this corona potentially affects particle uptake, fate, absorption, distribution, and elimination in vivo. This study explored relationships between the biological interactions of calcium carbonate particles and their biokinetics.

Methods: We examined the effects of food grade calcium carbonates of different particle size (nano [N-Cal] and bulk [B-Cal]: specific surface areas of 15.8 and 0.83 m(2)/g, respectively) on biological interactions in in vitro simulated physiological fluids, ex vivo biofluids, and in vivo in gastrointestinal fluid. Moreover, absorption and tissue distribution of calcium carbonates were evaluated following a single dose oral administration to rats.

Results: N-Cal interacted more with biomatrices than bulk materials in vitro and ex vivo, as evidenced by high fluorescence quenching ratios, but it did not interact more actively with biomatrices in vivo. Analysis of coronas revealed that immunoglobulin, apolipoprotein, thrombin, and fibrinogen, were the major corona proteins, regardless of particle size. A biokinetic study revealed that orally delivered N-Cal was more rapidly absorbed into the blood stream than B-Cal, but no significant differences were observed between the two in terms of absorption efficiencies or tissue distributions. Both calcium carbonates were primarily present as particulate forms in gastrointestinal fluids but enter the circulatory system in dissolved Ca(2+), although both types showed partial phase transformation to dicalcium phosphate dihydrate. Relatively low dissolution (about 4%), no remarkable protein-particle interaction, and the major particulate fate of calcium carbonate in vivo gastrointestinal fluids can explain its low oral absorption (about 4%) regardless of particle size.

Conclusion: We conclude that calcium carbonate nanoparticles can act more actively with biological matrices in vitro and ex vivo, but that in vivo, their biological interactions and biokinetics are not affected by particle size.

No MeSH data available.


Related in: MedlinePlus

Plasma concentration-time curves (A–D) and tissue distribution (E, F) of calcium carbonates after a single (A, B), or 14 days of daily oral treatment (C–F) to rats.Notes: Biokinetic data are presented as increase in calcium levels after subtracting the basal plasma calcium levels observed in untreated controls; (A) Biokinetics after administering a single dose to male rats; (B) Biokinetics after administering a single dose to female rats; (C) Biokinetics after 14-days of daily oral treatment in male rats; (D) Biokinetics after 14-days of daily oral treatment in female rats; (E) Tissue distribution in male rats; (F) Tissue distribution in female rats. (a) and (b) is used when there is no significant difference between two groups (control and N-Cal/N-Cal and B-Cal), but significant difference is found when three groups (control, N-Cal, B-Cal) are compared.Abbreviations: B-Cal, bulk calcium carbonates; N-Cal, nano calcium carbonates.
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f3-ijn-10-2273: Plasma concentration-time curves (A–D) and tissue distribution (E, F) of calcium carbonates after a single (A, B), or 14 days of daily oral treatment (C–F) to rats.Notes: Biokinetic data are presented as increase in calcium levels after subtracting the basal plasma calcium levels observed in untreated controls; (A) Biokinetics after administering a single dose to male rats; (B) Biokinetics after administering a single dose to female rats; (C) Biokinetics after 14-days of daily oral treatment in male rats; (D) Biokinetics after 14-days of daily oral treatment in female rats; (E) Tissue distribution in male rats; (F) Tissue distribution in female rats. (a) and (b) is used when there is no significant difference between two groups (control and N-Cal/N-Cal and B-Cal), but significant difference is found when three groups (control, N-Cal, B-Cal) are compared.Abbreviations: B-Cal, bulk calcium carbonates; N-Cal, nano calcium carbonates.

Mentions: The plasma concentration-time profiles of B-Cal and N-Cal in rats after a single oral dose are presented in Figure 3A–D. Increased plasma calcium concentrations were determined by subtracting control plasma calcium levels from total plasma calcium levels, as determined by ICP-AES. Peak concentrations were observed at 1 and 2 hours postadministration for N-Cal and B-Cal, respectively, with no effect due to sex of the animal, and these concentrations then decreased rapidly within 4 hours. Biokinetic parameters, obtained from Figure 3, showed significantly higher Cmax values for N-Cal than B-Cal (Table 4). However, other parameters such as the AUC, T1/2, and MRT values of B-Cal and N-Cal were similar. After 14 days of daily dosing, similar results were obtained (Figure 3; Table 4). Tmax values for N-Cal and B-Cal were 1 and 2 hours, respectively, and high Cmax values were obtained for N-Cal, whereas, T1/2 and MRT values were slightly higher for B-Cal. It should be noted that no abnormal behaviors, symptoms, or body weight changes were observed during the 14-day treatment period. Absorption amounts calculated based on AUC values are presented in Table 4. About 4%–5% of B-Cal and N-Cal entered the blood stream, and this was unaffected by particle size, sex, or number of treatments.


The fate of calcium carbonate nanoparticles administered by oral route: absorption and their interaction with biological matrices.

Lee JA, Kim MK, Kim HM, Lee JK, Jeong J, Kim YR, Oh JM, Choi SJ - Int J Nanomedicine (2015)

Plasma concentration-time curves (A–D) and tissue distribution (E, F) of calcium carbonates after a single (A, B), or 14 days of daily oral treatment (C–F) to rats.Notes: Biokinetic data are presented as increase in calcium levels after subtracting the basal plasma calcium levels observed in untreated controls; (A) Biokinetics after administering a single dose to male rats; (B) Biokinetics after administering a single dose to female rats; (C) Biokinetics after 14-days of daily oral treatment in male rats; (D) Biokinetics after 14-days of daily oral treatment in female rats; (E) Tissue distribution in male rats; (F) Tissue distribution in female rats. (a) and (b) is used when there is no significant difference between two groups (control and N-Cal/N-Cal and B-Cal), but significant difference is found when three groups (control, N-Cal, B-Cal) are compared.Abbreviations: B-Cal, bulk calcium carbonates; N-Cal, nano calcium carbonates.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4376267&req=5

f3-ijn-10-2273: Plasma concentration-time curves (A–D) and tissue distribution (E, F) of calcium carbonates after a single (A, B), or 14 days of daily oral treatment (C–F) to rats.Notes: Biokinetic data are presented as increase in calcium levels after subtracting the basal plasma calcium levels observed in untreated controls; (A) Biokinetics after administering a single dose to male rats; (B) Biokinetics after administering a single dose to female rats; (C) Biokinetics after 14-days of daily oral treatment in male rats; (D) Biokinetics after 14-days of daily oral treatment in female rats; (E) Tissue distribution in male rats; (F) Tissue distribution in female rats. (a) and (b) is used when there is no significant difference between two groups (control and N-Cal/N-Cal and B-Cal), but significant difference is found when three groups (control, N-Cal, B-Cal) are compared.Abbreviations: B-Cal, bulk calcium carbonates; N-Cal, nano calcium carbonates.
Mentions: The plasma concentration-time profiles of B-Cal and N-Cal in rats after a single oral dose are presented in Figure 3A–D. Increased plasma calcium concentrations were determined by subtracting control plasma calcium levels from total plasma calcium levels, as determined by ICP-AES. Peak concentrations were observed at 1 and 2 hours postadministration for N-Cal and B-Cal, respectively, with no effect due to sex of the animal, and these concentrations then decreased rapidly within 4 hours. Biokinetic parameters, obtained from Figure 3, showed significantly higher Cmax values for N-Cal than B-Cal (Table 4). However, other parameters such as the AUC, T1/2, and MRT values of B-Cal and N-Cal were similar. After 14 days of daily dosing, similar results were obtained (Figure 3; Table 4). Tmax values for N-Cal and B-Cal were 1 and 2 hours, respectively, and high Cmax values were obtained for N-Cal, whereas, T1/2 and MRT values were slightly higher for B-Cal. It should be noted that no abnormal behaviors, symptoms, or body weight changes were observed during the 14-day treatment period. Absorption amounts calculated based on AUC values are presented in Table 4. About 4%–5% of B-Cal and N-Cal entered the blood stream, and this was unaffected by particle size, sex, or number of treatments.

Bottom Line: N-Cal interacted more with biomatrices than bulk materials in vitro and ex vivo, as evidenced by high fluorescence quenching ratios, but it did not interact more actively with biomatrices in vivo.A biokinetic study revealed that orally delivered N-Cal was more rapidly absorbed into the blood stream than B-Cal, but no significant differences were observed between the two in terms of absorption efficiencies or tissue distributions.We conclude that calcium carbonate nanoparticles can act more actively with biological matrices in vitro and ex vivo, but that in vivo, their biological interactions and biokinetics are not affected by particle size.

View Article: PubMed Central - PubMed

Affiliation: Department of Food Science and Technology, Seoul Women's University, Seoul, Republic of Korea.

ABSTRACT

Background: Orally administered particles rapidly interact with biological fluids containing proteins, enzymes, electrolytes, and other biomolecules to eventually form particles covered by a corona, and this corona potentially affects particle uptake, fate, absorption, distribution, and elimination in vivo. This study explored relationships between the biological interactions of calcium carbonate particles and their biokinetics.

Methods: We examined the effects of food grade calcium carbonates of different particle size (nano [N-Cal] and bulk [B-Cal]: specific surface areas of 15.8 and 0.83 m(2)/g, respectively) on biological interactions in in vitro simulated physiological fluids, ex vivo biofluids, and in vivo in gastrointestinal fluid. Moreover, absorption and tissue distribution of calcium carbonates were evaluated following a single dose oral administration to rats.

Results: N-Cal interacted more with biomatrices than bulk materials in vitro and ex vivo, as evidenced by high fluorescence quenching ratios, but it did not interact more actively with biomatrices in vivo. Analysis of coronas revealed that immunoglobulin, apolipoprotein, thrombin, and fibrinogen, were the major corona proteins, regardless of particle size. A biokinetic study revealed that orally delivered N-Cal was more rapidly absorbed into the blood stream than B-Cal, but no significant differences were observed between the two in terms of absorption efficiencies or tissue distributions. Both calcium carbonates were primarily present as particulate forms in gastrointestinal fluids but enter the circulatory system in dissolved Ca(2+), although both types showed partial phase transformation to dicalcium phosphate dihydrate. Relatively low dissolution (about 4%), no remarkable protein-particle interaction, and the major particulate fate of calcium carbonate in vivo gastrointestinal fluids can explain its low oral absorption (about 4%) regardless of particle size.

Conclusion: We conclude that calcium carbonate nanoparticles can act more actively with biological matrices in vitro and ex vivo, but that in vivo, their biological interactions and biokinetics are not affected by particle size.

No MeSH data available.


Related in: MedlinePlus