Lipid-Core Micelles for Targeted Drug Delivery

Vladimir   P.   Torchilin

Abstract

Micelles, self-assembling nanosized colloidal particles with a hydrophobic core and hydrophilic shell are currently successfully used for the solubilization of various poorly soluble pharmaceuticals and demonstrate a series of attractive properties as drug carriers. Polymeric micelles, i.e. micelles formed by amphiphilic block co-polymers possess high stability both in vitro and in vivo and good biocompatibility. Among those micelles, lipid-core micelles, i.e. micelles formed by conjugates of soluble copolymers with lipids (such as polyethylene glycol-phosphatidyl ethanolamine conjugate, PEG-PE) are of special interest. These micelles can effectively solubilize a broad variety of poorly soluble drugs (anticancer drugs in particular) and diagnostic agents. Drug-loaded lipid-core micelles can spontaneously target body areas with compromised vasculature (tumors, infarcts) via the enhanced permeability and retention (EPR) effect. Lipid-core mixed micelles containing certain specific components (such as positively charged lipids) are capable of escaping endosomes delivering incorporated drugs directly into the cell cytoplasm. Various specific targeting ligand molecules (such as antibodies) can be attached to the surface of the lipid-core micelles and bring drug-loaded micelles to and into target cells. Lipid-core micelles carrying various reporter (contrast) groups may become the imaging agents of choice in different imaging modalities.

Keywords: pharmaceutical carriers, nanocarriers, drug targeting, polymeric micelles, poorly soluble drugs, polyethylene glycollipid conjugates, intracellular drug delivery, diagnostic agents