Targeted Drug Delivery - Nanomaterials for Medical Applications - page 181

dextran-iron oxide and dextran-poly(isobutylcyanoacrylate) NPs are exten-
sively coated with known opsonins such as complement, fibronectin, and fibrin-
ogen 14 , 15 but the significance of these interactions in the NP clearance in vivo
is not known. Others suggested that dextran-iron oxide NPs could be directly
recognized through a receptor mechanism that is still unknown but without
plasma opsonin involvement. 16 This claim in vivo is difficult to prove or dis-
prove because of the presence of plasma proteins in the body.
In general, the drug is dissolved, entrapped, adsorbed, attached, and/or
encapsulated into or onto an NM ( Figure 5.1 ). The NMs can be constructed to
possess different drug loading and release characteristics for the best delivery
of the therapeutic agent. 3,4,17 Various forms of NMs have been used as drug
delivery system. The NMs may be in the form of a nanocapsule where a drug
is confined to a cavity surrounded by a polymer membrane 1 or a nanosphere in
which the drug is physically and or chemically dispersed uniformly inside or
outside the structure. The NMs may be in the form of liposomes, dendrimers,
magnetic NPs, hydrogels, polymers, or semiconductor NMs.
The use of conventional drug carriers (adjuvants) leads to modification of
the drug biodistribution profile as it is mainly delivered to the mononuclear
phagocyte system (MPS), 18 also called reticuloendothelial system (RES) in the
liver, spleen, lungs, and bone marrow. The NMs may be recognized by the host
immune system when i.v. administered, thus, cleared by phagocytes from circu-
lation. 19 Aside from size, the NM hydrophobicity determines the level of blood
components that binds on the particle surface leading to a cascade of events that
result in an immune response. The NMs hydrophobicity influences the in vivo
fate of NMs 20 in such a way that once in the blood stream, nonmodified NMs
are rapidly opsonized and cleared by the MPS. 21
For successful targeted drug delivery in vivo, it is necessary to reduce the
opsonization to prolong the circulation of NMs. One way to achieve this is to
FIGURE 5.1 Schematic diagram of an NM with (A) encapsulated or (B) surface-bound drugs.
The NM drug carrier is modified with a targeting molecule. (For color version of this figure, the
reader is referred to the online version of this topic)