Effect of phosphatidylcholine on the stability and lipolysis of nanoemulsion drug delivery systems.

ABSTRACT

Phosphatidylcholines (PCs) have been widely used in pharmaceutical research. Unfortunately, our understanding of how PCs influence the in vivo lipolysis process of drug delivery systems is still limited. In this study, PCs with fatty acid chains of varying lengths and saturability were used as emulsifiers to prepare curcumin-loaded nanoemulsions (Cur-NEs). The differences in particle size as well as drug and free fatty acid release during the lipolysis process were studied in a simulated blood environment. Furthermore, the pharmacokinetics and antitumor efficacy of Cur-NEs were evaluated in mice. The prepared 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)-stabilized Cur-NEs showed similar particle size and stability during storage but exhibited different lipolysis behaviors in vitro and in vivo. Due to the gel state of DPPC in the physiological environment, DPPC-stabilized Cur-NEs had low binding affinity with proteins and maintained their integrity in plasma, leading to sustained drug release, prolonged circulation time and enhanced antitumor efficacy in 4T1 tumor-bearing mice. In contrast, DOPC and DSPC-stabilized Cur-NEs were prone to coalescence in the plasma, resulting in rapid drug release and elimination from circulation. Our findings demonstrated that proper use of PCs is beneficial for obtaining desired transport behavior and drug therapeutic effects, providing guiding principles for rational design of nanodelivery systems.