Controlled release systems for DNA delivery

Abstract

Adapting controlled release technologies to the delivery of DNA has the potential to overcome extracellular barriers that limit gene therapy. Controlled release systems can enhance gene delivery and increase the extent and duration of transgene expression relative to more traditional delivery methods (e.g., injection). These systems typically deliver vectors locally, which can avoid distribution to distant tissues, decrease toxicity to nontarget cells, and reduce the immune response to the vector. Delivery vehicles for controlled release are fabricated from natural and synthetic polymers, which function either by releasing the vector into the local tissue environment or by maintaining the vector at the polymer surface. Vector release or binding is regulated by the effective affinity of the vector for the polymer, which depends upon the strength of molecular interactions. These interactions occur through nonspecific binding based on vector and polymer composition or through the incorporation of complementary binding sites (e.g., biotin -avidin). This review examines the delivery of nonviral and viral vectors from natural and synthetic polymers and presents opportunities for continuing developments to increase their applicability.

Dynamic analysis of DNA nanoparticle immobilization to model biomaterial substrates using combinatorial spectroscopic ellipsometry and quartz crystal microbalance with dissipation

“…Nonviral gene delivery approaches differ from the use of viral vectors in that they not only are less toxic, less immunogenic, and less costly to produce, but also suffer from being less efficient in gene delivery [3,4]. Nonviral gene complexes typically consist of circular, plasmid DNA, which is highly negatively charged, electrostatically complexed with cationic lipids or polymers to form lipoplex and polyplex DNA-nanoparticles (DNA-NPs), respectively [4][5][6]. There have been many efforts to increase the efficiency of nonviral complex delivery, including alternative delivery strategies like substrate-mediated gene delivery (SMD).…”

Evaluation of fibrin-based gene-activated matrices for BMP2/7 plasmid codelivery in a rat nonunion model

“…Therefore, several strategies have been developed to overcome barriers to non-viral gene delivery and to enhance transfection efficacies [14,15]. The use of cationic polymers or lipoplexes and other reagents for non-viral gene delivery is a well established method which can significantly increase transfection efficacies in vitro and in vivo [16][17][18].…”

Physicochemical properties of polymers: An important system to overcome the cell barriers in gene transfection

“…The scaffold acts as a mechanical vehicle for cell growth and controlled release of gene 42,43 . In substrate-mediated delivery or so-called 'solid-phase transfection" for localizing gene delivery, the DNA was condensed with cationic polymers earlier than encapsulation in the polymer matrix, which reduced the particle size, protected DNA from degradation, and increased the cell internalization 44 .…”