Membrane/Core Nanoparticles for Delivery of Therapeutic Nucleic Acid - Nanotechnology for the Delivery of Therapeutic Nucleic Acids - page 62

42

albumin, these particles accumulate mostly in the lung and the

liver with a rapid blood clearance when dissociated from the bound
serum proteins.
In the development of a new and efficient delivery system for
therapeutic nucleic acid, physical and chemical properties of NPs
should be carefully considered since the size, shape, and surface
chemistry critically determine the PK profile and biodistribution of
the particles. One may achieve a prolonged circulation in the blood
and a reduction of RES uptake by simply manipulating the size,
charge, and surface chemistry of the NPs. However, there are still
several problems to be resolved for a successful drug delivery even
with improved PK and biodistribution. A challenge then will be how
to achieve sufficient intracellular delivery and release of the drug
cargo from the particles after internalization. These aspects will be
discussed below.

3.3 Current Non-Viral Carrier Systems

There are several different non-viral carriers based on their
material composition. It is important to select a suitable material
based on the nucleic acid cargo in order to effectively incorporate
the cargo and also to enhance the gene silencing effect on the
target gene.

2

The material most extensively studied for the non-
viral delivery system is liposome. Liposomes are spherical vesicles
with an aqueous interior surrounded by a phospholipid bilayer
membrane. Liposomes can efficiently carry the encapsulated cargo
into the cells by endocytosis and enhance drug delivery. Cationic
lipids are usually used to condense negatively charged nucleic acid
to form a nanostructure known as a lipoplex.

43

Cationic lipids not
only sufficiently encapsulate nucleic acid and protect it from serum
degradation but also induce destabilization of the endosomal
membrane in order to release the nucleic acid cargo into the
cytoplasm.

1, 44, 45

Since cationic liposomes display a high transfection
efficiency and are easy to use, several commercially available lipo-
some formulations have already been developed, e.g., Lipofectamine™
and Oligofectamine™.

46

However, these lipoplexes usually have

a short half-life due to their excess positive charges and

are also toxic to the host. Therefore, it is essential to consider the
balance between stability, efficacy, and potential toxicity based on
the electrostatic interactions between nucleic acid and lipids.

in vivo

47