Design and biological activity of novel stealth polymeric lipid nanoparticles for enhanced delivery of hydrophobic photodynamic therapy drugs.

Abstract Advances in in vivo stability and preferential tumor uptake of cancer nanomedicine are warranted for effective chemotherapy. Here, we describe a novel nanoformulation using an unconventional polymeric tubule-forming phospholipid, DC 8,9 PC. We report that DC 8,9 PC transitions to stable vesicles (LNPs) in the presence of PEGylated lipid (DSPE-PEG2000); the resulting DC 8,9 PC:DSPE-PEG2000 LNPs efficiently included a hydrophobic PDT drug, HPPH. Remarkably, these LNPs incorporated unusually high DSPE-PEG2000 concentrations; LNP 10 -HPPH and LNP 20 -HPPH (10 & 20 mol% PEGylated lipid, respectively) exhibited >90% serum stability at 37 °C. Increased PEGylation in the LNPs correlated with enhanced tumor accumulation in intravenously injected HT29 tumor mouse xenographs. Colon-26 bearing BALB/c mice, intravenously injected with LNP 20 -HPPH showed superior PDT efficacy and animal survival (no tumor recurrence up to 100 days) as compared to a formulation currently used in clinical trials. Taken together, we present a simple stealth binary lipid nanosystem with enhanced efficiency of tumor accumulation and superior therapeutic efficacy. Graphical Abstract Inclusion of a PEG lipid in a non-bilayer forming polymeric lipid, DC8,9PC results in the formation of nano-sized vesicles (LNPs), not reported earlier. These vesicles efficiently incorporate a hydrophobic drug (HPPH) and remain stable upon storage at room temperature, as well as in the presence of serum components. The HPPH-loaded LNPs exhibit better tumor accumulation and show enhanced tumor cure in comparison to currently used formulation in clinical trials for this drug for its PDT efficacy. Unlabelled Image [ABSTRACT FROM AUTHOR]