Dynamic drug release state and PEG length in PEGylated liposomal formulations define the distribution and pharmacological performance of drug

To optimize the therapeutic efficacy of active pharmaceutical ingredients, various lipid-based drug delivery systems have been developed. In particular, due to the various advantages, most of the lipid-based nanoformulation products on the market contain the poly(ethylene glycol) (PEG) block on the carrier. However, the effect of PEG length on pharmacokinetic (PK) profile, nanoparticle distribution, and pharmacological efficacy of the encapsulated drug have not been explored fully. Here, we assessed the effects of PEG length on the distribution and pharmacological efficacy of doxorubicin (Dox)-loaded liposomal formulations. Compared to PEG-Lipo 2 K, PEG-Lipo 10 K increased the drug concentration in blood at 24 and 48 h and the extent of particle accumulation at the tumor site due to the enhanced blood circulation time of the nanoparticles having higher PEG length. However, as the drugs begin to be released from the carrier at the point of administration, the drug concentration at that later time point drops to 4% or less compared to that of the initial time points. Thus, the pharmacological efficacy among the PEG-Lipo formulations did not differ significantly, which could be attributed to their dynamic drug-releasing characteristics during circulation in the blood. These findings suggest that although PEG length plays a critical role in the particle and drug distribution of the formulations, it does not affect the therapeutic efficacy of the incorporated drug because of the dynamic character of drug-loaded PEG-Lipo structures.