Biomedical Engineering Reference
In-Depth Information
Using poly(b-benzyl L-aspartate) (PBLA) as a macromolecular guest, core-shell
structured spherical nano-assemblies of 90.6 nm can be constructed. The core of
assemblies composed of hydrophobic PBLA chain can accommodate hydrophobic
drugs, while the cationic shell can complex with pDNA. Dexamethasone (DEX), a
potent steroidal anti-inflammatory drug can be efficiently loaded into and released
from the PEI-CD/PBLA nanoparticles in a sustained manner. Gel retardation com-
bined with EtBr exclusion assays demonstrated that the pDNA could be complexed
with PEI-CD/PBLA assemblies to form a condensed structure when the weight
ratio was higher than 0.6. Cell culture experiments suggested that pDNA encoding
red fluorescence protein can be transfected and expressed in osteoblast cells, using
the polyplexes based on the assembled host-guest nanoparticles. Interestingly,
introducing DEX into the polyplexes can increase the transfection efficiency as
well as dramatically decrease the cytotoxicity of assemblies. The decreased cyto-
toxicity was considered to be related to the anti-inflammatory and immunosuppres-
sive activity of DEX that can inhibit proinflammatory cytokines such as tumor
necrosis factor a (TNF-a) and antagonize the activation of the NF-kB pathway by
direct and indirect mechanisms.
7
Nonviral Therapeutics in Clinical Trials
It is clear that most of the clinically studied gene delivery vectors are based on
viruses. Whereas a variety of delivery vectors have been studied for gene therapy,
most of them are still in the laboratory stage. Currently, lipoplexes and polyplexes
are two types of nonviral vectors that have been extensively studied for clinical
trials. Below we list some examples where the nonviral vectors, mainly lipoplex
and polyplex based nanomedicines have, at least in part showed their success in the
therapy of diseases such as cystic fibrosis, HIV, and various cancers.
7.1
Clinical Trials of Lipoplexes Vectors
Among the various nonviral vectors, lipoplexes have been the most intensively
studied carriers. Considerable amount of CL-based vectors have been evaluated in
clinical trials for the therapy of diseases varying from cancer, cystic fibrosis, HIV,
AAT deficiency, to cardiovascular diseases (Dass 2004 ; Davis and Cooper 2007 ;
Rubanyi 2001 ; Edelstein et al. 2004, 2007 ).
In 1993, Nabel et al. reported the first clinical gene therapy of melanoma using
DNA-liposome complexes (Nabel et al. 1993 ). Lipoplexes containing pDNA
encoding a foreign major histocompatibility complex protein (HLA-B7) were
locally injected into the melanoma nodule of HLA-B7-negative patients with
advanced melanoma. No complications were observed during six courses of
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