Parenteral Delivery of Peptides and Proteins - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 559

Hence, a method to associate the protein to the preformed nanoparticle surface by adsorp-
tion has been investigated. This technique can be performed in an aqueous solution and
at a low temperature, thus improving the prospects for preserving the activity of sensitive
protein and peptide molecules [261] .
Polymeric materials used for the formulation of nanoparticles include synthetic
polymers such as PLA, PLGA [148,192] , poly(-caprolactone) (PCL), poly(methyl
methacrylates), and poly(alkyl cyanoacrylates) [262,188] , or natural polymers as
albumin, gelatin, alginate, collagen, or chitosan. Research has also been extended
to PEGylation of nanoparticles to achieve prolonged circulation [263,264] . PEG-
coated nanoparticles have been found to be of great potential in therapeutic applica-
tion for controlled release of drugs and site-specific drug delivery, as investigated
with the TNF- delivery using gold nanoparticles [265,266] . These nanoparticles
exhibit stearic repulsion, which results from a loss of configurational entropy of the
bound PEG chains [267] . In addition, the hydrophilic PEG can form a hydrated outer
shell, which protects the nanoparticles from being quickly uptaken by the RES [268] ,
extends the half-life of drugs, and alters their tissue distribution. These nanoparticles
have been highly investigated for protein and peptide encapsulation for therapeutic
delivery [265,266] .
Poly(vinyl alcohol) (PVA) hydrogel nanoparticles have been prepared by using
a water-in-oil emulsion technology plus cyclic freezing-thawing process. The PVA
hydrogel nanoparticles prepared by this method are suitable for P/P drug delivery
because formation of the hydrogel does not require crosslinking agents or other adju-
vants and does not involve any residual monomer. Particularly, there is no emulsifier
involved in this new method [269] . Nanoparticles for hormone delivery can be pre-
pared from smart polymers which shows pH, or temperature-responsive drug release
profile, exemplified by poly(acrylic acid), PMAA, a pH-responsive polymer due to
its pH-dependent ionization and thereby hydration degree. The maximum volume
change in PMAA occurs at a pH around its p K a [270-274] . In vaccine development,
protein-coated, wax-based nanoparticles have also been shown to increase immune
responses significantly [275,276] , thus demonstrating high protein delivery. Table
11.7 summarizes examples of proteins and peptides delivered in various polymeric
nanoparticles discussed in this section.
In general, one of the drawbacks associated with the formulation of nanoparticles
is the initial burst and the incomplete release of the encapsulated protein, which may
influence its potential as a drug delivery system [279] . Although to some extent the
drawback can be controlled by optimizing particle size and the manufacturing tech-
niques applied [279] , it is still a challenge to formulate nanoparticulate drug delivery
systems for parenteral protein administration.
11.5.5 Solid Lipid Nanoparticles
SLNs ( Fig. 11.9 ) are colloidal particles composed of a biocompatible/biodegradable
lipid matrix that is solid at body temperature and exhibits size range between 100 and
400 nm. SLNs combine the advantages of colloidal drug carrier systems like liposomes,
polymeric nanoparticles, and emulsions, but avoid or minimize the drawbacks associated