doxorubicin dox

liposomes

therapeutic efficacy

plga nanoparticles

liposomal

micelles

Biophysical Journal

Paclitaxel (PTXL) is a hydrophobic drug that acts as a mitotic inhibitor, inducing apoptosis and halting the proliferation of tumor cells. PTXL is most often administered in hospitals in the patented formulation Taxol® whose solvents cause hypersensitivity reactions in addition to the side-effects of the chemotherapeutic PTXL drug. To improve the therapeutic efficacy of PTXL, it should be administered by a non-toxic delivery agent with tumor cell specificity. Lipid nanoparticles have many advantages as drug delivery vehicles including a diverse set of lipid building blocks to tune physical and chemical properties, low toxicity, and their ease of modular processing. Our recent study [1] revealed that loading PTXL in cationic liposomes (CLs) at a concentration lower than the membrane solubility limit (less than 3 mol%) may have short and long-term benefits for drug delivery outcomes compared to the CL formulation EndoTAG®, which employs CLs at the PTXL membrane solubility limit. In the work presented here, we consider the effects of lipid curvature, hydrophobic tail saturation, and inclusion of PEG-lipid on PTXL solubility in CLs, and we correlate the physical properties of the liposomes to PTXL delivery efficacy observed in in vitro cell studies. [1] Steffes et al. Distinct solubility and cytotoxicity regimes of paclitaxel-loaded cationic liposomes at low and high drug content revealed by kinetic phase behavior and cancer cell viability studies. Biomaterials 2017, 145, 242-255. DOI: 10.1016/j.biomaterials.2017.08.026.

Optimizing Cationic Liposome Composition for Hydrophobic Drug Loading and Delivery to Human Cancer Cells