Polysaccharides as Nanomaterials for Therapeutics - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 141

approach for ischemic conditions was shown to generate new
blood vessels in vivo . However, intravenously injected VEGF was
not clinically successful and implantable controlled release devices
have shown that localized and sustained release of VEGF is required
for its favorable action. Nanoparticles of ~250 nm were prepared
in which the heparin-binding domain of VEGF was utilized to bind
the polyanion dextran sulfate. The encapsulation efficiency of VEGF
was high (85%) and controlled release (near linear) of active VEGF
was persisted was persistent for more than 10 days. The activity
of VEGF was determined by ELISA and by the ability to stimulate
endothelial cell proliferation (mitogenic assay). PEC containing
diff erent polycations (polyethylenimine and poly-L-lysine) were also
tested; however, chitosan−dextran sulfate complexes were preferred
because of their biodegradability, desirable particle size, higher
entrapment efficiency, controlled release, and mitogenic activity. In
a following study by the same group [119], Repifermin ® -containing
nanoparticles were prepared in the same manner. Repifermin ® is a
truncated form of fibroblast growth factor-10 that exhibits promise
in wound-healing applications. The challenge of the delivery lies in
the instability of this protein. The resulting 250 nm nanoparticles
showed high encapsulation efficiency and the release of active
Repifermin ® was controlled for more than 10 days. In addition, the
mitogenic activity of Repifermin ® on human umbilical cord vascular
endothelial cells was only demonstrated for encapsulated and not
free Repifermin ® .
Zinc-stabilized complexes of dextran sulfate and polyethylenimine
have been used for the delivery of proteins [62], DNA, and the poorly
water-soluble antifungal agent amphotericin B [120]. The preparation
method of these nanoparticles was complex coacervation, a method
that was usually used for microencapsulation [120]. The eff ects of
preparation conditions and composition on the physicochemical
properties of the particles have been determined [120]. The sizes
of the amphotericin B-containing nanoparticles were 100-600 nm,
a zeta potential of 30 mV and drug recovery efficiency of up to 85%.
Particle size was shown to be controlled by processing parameters
such as the pH of the PEI solutions, the ratio of the two polymers
and the concentrations of dextran sulfate and zinc sulfate. The
amphotericin B-containing nanoparticles displayed no toxicity in
tissue culture in contrast to free drug and were almost as efficacious
as free drug in killing Candida albicans .