Achieving Effective Vascular and Extravascular Targeted Drug Delivery with Lipid Nanoparticles and Micelles

G. Lanza
Washington University School of Medicine,
United States

Keywords: cancer nanotechnolgy, Lipid Nanoparticles, Micelles


Many drugs incorporated into nanosystems, targeted or not, are substantially lost during circulation to the target. However, favorably altering the pharmacokinetics and volume of distribution of systemic drug delivery can offer greater efficacy with lower toxicity, leading to new prolonged-release nanoexcipients. The concept of achieving Paul Erhlich’s inspired vision of a “magic bullet” to treat disease has been largely unrealized due to unstable nanomedicines, nanosystems achieving low drug delivery to target cells, poor intracellular bioavailability of endocytosed nanoparticle payloads, and the substantial biological barriers of extravascular particle penetration into pathological sites. Sn2 phospholipid prodrugs in conjunction with contact-facilitated drug delivery prevent premature drug diffusional loss during circulation and increase target cell bioavailability. The Sn2 phospholipid prodrug approach applies equally well for vascular constrained lipid-encapsulated particles and for micelles the size of proteins that penetrate in the bone. At one time Nanomedicine was considered a “Grail Quest” by its loyal opposition and even many in the field adsorbing the pains of a long learning curve about human biology and particles. However, Nanomedicine with innovations like Sn2 phospholipid prodrugs has finally made “made the turn” toward meaningful translational success.