Effects of particle size on blood clearance and tissue uptake of lipid emulsions with different triglyceride compositions.

BACKGROUND

Particle size of IV lipid emulsions affects the catabolism of long-chain triglyceride (LCT) emulsions, but little is known about its effect on the catabolism of medium-chain triglyceride (MCT)- and fish oil (FO)-containing emulsions.

METHODS

Large (VLDL size), intermediate, and small (IDL size) emulsions with different triglyceride (TG) compositions were labeled with [3H]cholesteryl oleoyl ether: LCT (triolein 100%), MCT:LCT (trioctanoin:triolein 50%:50%), MCT:LCT:FO (trioctanoin:triolein:triDHA 50%:40%:10%), and FO (triDHA 100%). Emulsions (0.4 mg TG/mouse) were injected into C57BL/6J mice, and blood clearance and tissue uptake of emulsion particles were determined.

RESULTS

Large emulsion particles had 2- to 3-fold faster fractional catabolic rates (FCR) compared with small particles with the same TG content. There was 1.5- to 2.0-fold higher FCR of large FO-containing emulsions (FO and MCT:LCT:FO) compared with large LCT and MCT:LCT emulsions, whereas effects of FO on FCR in small emulsions were not observed. Large FO-containing emulsions were taken up more by adipose tissue compared with small particles with concomitant decreases in hepatic uptake. Preinjection of heparin reduced heart and adipose uptakes of FO and MCT:LCT:FO emulsions with increased uptake by liver, suggesting a role of lipoprotein lipase in catabolism of FO-containing emulsions.

CONCLUSIONS

In a mouse model, FO addition to large emulsions increased blood clearance and changed organ delivery. In contrast, there was no or little effect when particle size became smaller. We hypothesize that in humans, FO addition to lipid emulsions can help target emulsion delivery to certain extrahepatic tissues, a factor that may be of use for delivering specific fatty acids, or even drugs, to specific organs.