Targeted drugs and nanomedicine: present and future.
Packaging small-molecule drugs into nanoparticles improves their bio-availability, 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, chimeric 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.
Debbage
Paul
P
Department of Anatomy, Histology and Embryology, Medical University of Innsbruck, Muellerstrasse 59, Innsbruck, Austria. Paul.Debbage@i-med.ac.at
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000627:therapeutic use; D004333:Drug Administration Routes; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends; D015195:Drug Design; D005544:Forecasting; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use; D050997:Nanomedicine / Q000379:methods* / Q000639:trends; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000138:chemical synthesis; D015202:Protein Engineering / Q000379:methods
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D004364:Pharmaceutical Preparations