Therapeutic Approaches Using Polyplexes

Table 2 lists an example of therapeutic concepts evaluated in animal models. Using the first targeted in vivo gene delivery system developed,[13] Wu and colleagues demonstrated hepatocyte-specific gene transfer of the LDL receptor in a rabbit animal model for familial hypercho-lesterolemia. This resulted in a temporary amelioration of the disease phenotype.[25] In analogous manner, the albumin serum levels of Nagase analbuminemic rats were transiently raised by human albumin gene delivery.[14]

For cancer, Gautam and colleagues[18] successfully delivered PEI polyplexes expressing the p53 gene as aerosol through the airways to established melanoma lung metastases, which, especially in combination with 9-nitrocamptothecin chemotherapy, resulted in tumor growth inhibition.

Polyplexes with appropriate surface shielding can target the tumor tissue and exploit the unique neo-vasculature for extravasation from the blood stream (compare Fig. 1) and delivery of therapeutic genes into the tumor tissue. Repeated systemic application of transferrin- and/or PEG-shielded polyplexes encoding tumor necrosis factor alpha (TNF-alpha) into tumor-bearing mice induced expression in tumor cells close to the feeding blood vessels, which triggers TNF-mediated destruction of the tumor vasculature, tumor necrosis, and inhibition of tumor growth as demonstrated in several

Table 2 Examples for therapeutic strategies using polyplexes

Polyplex system

Delivery mode

Gene (target organ)

Therapeutic result

Reference

ASOM-polylysine

Intravenous (rat)

Human albumin (liver)

Human albumin in serum

[14]

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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