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

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.

Interactions between Food Additive Silica Nanoparticles and Food Matrices

“…Meanwhile, blue shift indicating protein denaturation or deformation was only observed in casein solution at 5 mg/ml NP concentration at 40°C after 48 h. Moreover, overall fluorescence quenching ratios were < 40%, except incubation for 7 d at 25°C. These results suggest that the interactions between SiO 2 NPs and proteins are not strong compared to other NP interactions which induce more than 80% quenching (Iosin et al, 2009 ; Chatterjee et al, 2010 ; Lee et al, 2015 ).…”

Synthesis and Characterization of Gefitinib and Paclitaxel Mono and Dual Drug-Loaded Blood Cockle Shells (Anadara granosa)-Derived Aragonite CaCO3 Nanoparticles

“…In contrast, positively charged calcium carbonate nanoparticles were synthesized by Lee et al where the source of calcium carbonate was ground seashells. The same study gives the striking data of the size measured using SEM and DLS to be~30 nm and 2187 nm [82], where the size measured with SEM is about 72 times lesser than the size obtained by DLS.…”

Pharmacokinetics of Free Oxytetracycline and Oxytetracycline Loaded Cockle Shell Calcium Carbonate-Based Nanoparticle in BALB/c Mice

“…The longer time taken to reach the Tmax of OTC-CNP at 0.167 h may be because of the slow release of OTC from CNP (29). In addition, the absorption of calcium carbonate nanoparticles following administration can be attributed to its size (62.4 ± 20.68 nm) and negative charge (6,31). At this size, it is easily transported from the peritoneum via the stomata and lymphatic system.…”