Parenteral Delivery of Peptides and Proteins - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 558

The liposomal depot for prolonged delivery of proteins and peptides was also
explored to overcome certain drawbacks of P/P therapeutics, and is discussed else-
where in this chapter.
In maintaining protein integrity and to prolong the effect of a protein, a liposo-
mal formulation is the most attractive choice. Liposomal suspensions are reasonably
sturdy and can be lyophilized and reconstituted, provided that lyoprotectants are
included [236] .

11.5.4 Nanoparticles
Nanotechnology focuses on formulating therapeutic agents in biocompatible nano-
composites such as nanoparticles, nanocapsules, micellar systems, and nanocon-
jugates. Nanoparticles as delivery systems for proteins and peptides have numerous
advantages over microparticles. Due to their subcellular and submicron size, nanopar-
ticles penetrate deeper into tissues through fine capillaries, facilitating delivery to var-
ious target organs such as the liver, spleen, lung, spinal cord, and lymph; they control
the release properties by modulating polymer composition, polymer biodegradability,
pH, ion, and/or temperature sensibility of materials; and they improve the utility of
drugs and reduce toxic side effects. Lipids can also be incorporated in the core of
nanoparticles for the sustained release of proteins, as investigated for lysozyme and
VEGF. Figure 11.8 gives diagrammatic view of core-shell nanoparticles [255,256] .
As a drug delivery system, nanoparticles can entrap drugs or biomolecules into their
interior structures and/or absorb drugs or biomolecules onto their exterior surface.
Further, nanoparticles can be delivered to distant target sites either by localized deliv-
ery using a catheter-based approach with a minimal invasive procedure [257] , or they can
be conjugated to a biospecific ligand that can direct them to the target tissue or organ
[258] . The water-oil-water double emulsion technique has been the most widely used
technique for protein micro- and nanoencapsulation. Many other investigated methods
require high shear forces and organic solvent to prepare nanoparticles, both of which are
usually detrimental to proteins. Solvent displacement has become a popular alternative
method for protein encapsulation, but it results in low encapsulation efficiency [259,260] .

Nanoparticle
interior

Figure 11.8 Schematic representation of
core-shell nanoparticles.

Nanoparticle
surface

Targeting
ligand

Nanoparticle
shell

Shell
payload

Interior
payload

Surface
payload

Surface
coating