Use of HPMA copolymers in gene delivery

Effective therapeutic application of gene drugs requires noninvasive and cost-effective methods for gene delivery, which should be safe for repetitive use and provide reproducible therapeutic effect. Systematic research efforts in the area of polyelectrolyte complexes of DNA with polycations (polyplexes) resulted in an increased understanding of the principles governing the biological activity of polyplexes and now permit rational design of increasingly more efficient vectors. Despite this tremendous progress, significant constrains limiting the efficiency of the gene delivery process mediated by polyplexes still remain, particularly when they are administered systemically.1 The growing emphasis on the systemic delivery of genes via intravenous injection reflects the need to gain access to disseminated and widespread disease targets, such as cancer cells, and to expand the available therapeutic modalities. To construct a delivery system suitable for systemic administration, a thorough understanding of the in vivo pharmacokinetic and disposition characteristics of the vector is important.2 The distribution and elimination patterns of systemically administered polyplexes largely follow general behavior observed for other macromolecules and nanoparticles, and depend mainly on the physicochemical properties of the carrier, such as size and molecular weight, electric charge, and hydrophilic/hydrophobic balance.3,4 Based on the accurate understanding of the relationship between the physicochemical properties of macromolecular carriers and their pharmacokinetics, it is often possible to effectively control their disposition properties.