Targeted Delivery of Nanoparticles
     Elizabeth Chambers- Long-Circulating Nanoparticles
     Sejal Sampat- Targeted Drug Delivery
    

     Long-Circulating Nanoparticles

                Polymeric nanoparticles have been extensively studied for use as intravascular
drug delivery vehicles. Polymeric particles potentially offer many advantages over traditional
intravascular methods of drug delivery. They can be used to encapsulate sensitive therapeutic
agents, thus protecting them from degradation and clearance in the vasculature while
maintaining a steady plasma concentration. Furthermore, sustained drug concentrations in
the blood reduce the required dose thus reducing the possibility of side effects. Sustained
release also decreases the dosing frequency thereby increasing patient compliance.
                Unfortunately polymeric particles are rapidly cleared from circulation by the
reticuloendothelial system (RES) preventing their effective use as sustained drug delivery
vehicles. When polymeric particles are introduced into vascular circulation they are
opsononized and subsequently removed from vascular circulation by macrophages primarily
located in the liver, spleen and lungs. Previous attempts to improve vascular circulation have
focused on coating the particles with polymer brushes, such as polyoxamines, polyoxamers,
and polyethylene glycol, to prevent opsononization. However, circulation lifetimes of surface-
modified particles are still limited.
                We are studying a novel method of increasing intravascular particle circulation by
anchoring the nanoparticles to the surface of red blood cells (RBCs). We have found that
particles adhered to RBCs can indeed escape phagocytosis due to the ability of RBCs to evade
macrophages. This method is motivated by the strategy adopted by certain bacteria, for
example hemobartonella, that adhere to RBCs and can remain in circulation for several weeks.
 

    Targeted Drug Delivery

                The majority of therapeutics in use today are not targeted to the site of disease in the
body. Instead, they are delivered systemically and become evenly distributed throughout the
body due to the lack of a targeting moiety. This method of delivery greatly reduces the efficacy
of therapeutics because there are many biological barriers that must be overcome before
reaching the target site. Non-targeted delivery also causes negative side effects associated with
the delivery of large doses of therapeutics and drug activation in non target sites. Targeting
therapeutics to specific sites in the body will increase the efficacy of drugs while reducing the
dose required along with negative side effects. The delivery of drugs to hard to reach places,
such as the brain, may also be possible.
                It is known that cells, tissues, and organs all display unique markers that may be
useful as targets for drug delivery. The development of microbial peptide display libraries, such
as phage and bacterial cell surface display, has made it easier to exploit the heterogeneity among
the different cell and tissue types. The use of these large peptide libraries allows the identification
of peptide - receptor interactions of the desired affinity and specificity by employing various
in vitro selection methods. These libraries also provide a means to discover novel cell
and tissue markers.
                In this collaborative project with Prof. Patrick Daugherty (Chemical Engineering,
UCSB), we are using bacterial cell surface peptide display libraries to discover peptides that have
strong binding affinity and specificity for various cells, tissues, and organs. These peptides will
then be used as targeting ligands on drug carriers and gene delivery vectors.