Packaging small-molecule drugs into nanoparticles improves their bioavailability,
bio-compatibility and safety profiles. Multifunctional particles carrying
large drug payloads for targeted transport, immune evasion and favourable drug release
kinetics at the target site, require a certain minimum size usually 30-300 nm diameter,
so are nanoparticles. Targeting particles to a disease site can signal the presence of the
disease site, block a function there, or deliver a drug to it. Targeted nanocarriers must
navigate through blood-tissue barriers, varying in strength between organs and highest
in the brain, to reach target cells. They must enter target cells to contact cytoplasmic
targets; specific endocytotic and transcytotic transport mechanisms can be used as
trojan horses to ferry nanoparticles across cellular barriers. Specific ligands to cell
surface receptors, antibodies and antibody fragments, and aptamers can all access such
transport mechanisms to ferry nanoparticles to their targets. The pharmacokinetics and
pharmacodynamics of the targeted drug-bearing particle depend critically on particle
size, chemistry, surface charge and other parameters. Particle types for targeting include
liposomes, polymer and protein nanoparticles, dendrimers, carbon-based nanoparticles
e.g. fullerenes, and others. Immunotargeting by use of monoclonal antibodies,
chimaeric antibodies and humanized antibodies has now reached the stage of clinical
application. High-quality targeting groups are emerging: antibody engineering enables
generation of human/like antibody (fragments) and facilitates the search for clinically
relevant biomarkers; conjugation of nanocarriers to specific ligands and to aptamers
enables specific targeting with improved clinical efficacy. Future developments depend
on identification of clinically relevant targets and on raising targeting efficiency of the
multifunctional nanocarriers. The complexity and expense of translational work with
nanoparticles has prompted regulatory agencies and funding organizations to adapt
regulatory frameworks and establish programs to facilitate preclinical testing.
Keywords: Antibody fragments, aptamers, clinical trials, immunotargeting, liposomes,
nanomedicine, nanoparticles, regulatory issues, targeted drugs, tissue barriers.
