Polysaccharides as Nanomaterials for Therapeutics - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 147

5.5.2 Hyaluronan-CoatedNanoparticles
The HA capsule of group A streptococci enables it to escape the host
immune response [148] and therefore provides long-term circulation.
This trait has been successfully adopted for the delivery of mitomycin
C using HA-coated liposomes (tHA-LIP) (Figure 5.4A) [141]. tHA-
LIP were 7-fold and 70-fold longer circulating in comparison with
uncoated liposomes and free mitomycin C in three murine tumor
models: BALB/c-bearing C-26 solid tumors; C57BL/6-bearing
B16F10.9, or D122 lung metastasis [141]. The HA on the tHA-LIP
was covalently attached using EDC via the glucuronic carboxylate
to phosphatidylethanolamine in the pre-formed liposomes. The
tHA-LIP demonstrated slower drug efflux and higher encapsulation
efficiency. In addition, since the eff ect of tHA-LIP is CD44 dependent,
these nanoparticles demonstrated significantly higher cytotoxicity in
vitro on CD44 overexpressing cells and increased drug accumulation
in tumors in vivo . The later resulted in decreased metastasis,
inhibition of tumor growth, and prolonged survival. These eff ects
were later demonstrated with doxorubicin-loaded tHA-LIP [3]. This
study also compared tHA-LIP with poly(ethylenglycol) (PEG)-coated
liposomes (“stealth” liposomes). This was done since PEGylation, a
common hydrophilic surface modification of drug delivery systems,
has demonstrated prevention of recognition by the immune system.
The tHA-LIP were long circulating more than all tested controls,
including uncoated and PEGylated liposomes in healthy and tumor-
bearing mice.
Recently, HA-coated paclitaxel-clusters (PTX-GAGs) have been
prepared for selective tumor targeting (Figure 5.4B) [149] ( see also
Chapter 1 in this topic). The aqueous insolubility of PTX was utilized
in this preparation by mixing it with lipids that self-assembled into
nano-size clusters. The clusters were then coated with HA to facilitate
targeting of CD44. When tested in vivo , these nanoparticles managed
to induce tumor arrest in a murine model of colon adenocarcinoma
and were significantly more potent than free PTX .
Targeting of CD44 was also demonstrated for liposomes
decorated with HA oligomers [140, 150]. Unlike in the preparation
of the previously described tHA-LIP, the HA oligosaccharides were
conjugated by reductive amination to phosphatidylethanolamine
prior to liposome preparation. The oligosaccharide-decorated
liposomes demonstrated CD44-dependent uptake, that could be