Poly(alkylene oxide) Copolymers for Nucleic Acid Delivery
ARMY INST OF SURGICAL RESEARCH FORT SAM HOUSTON TX
Pagination or Media Count:
The advancement of gene-based therapeutics to the clinic is limited by the ability to deliver physiologically relevant doses of nucleic acids to target tissues safely and effectively. Polymer and lipid based nano-assemblies have been successfully employed over the last couple of decades for the delivery of nucleic acids to treat a variety of disease states. Results of phase III clinical studies to evaluate the efficacy and biosafety of these gene delivery vehicles have been encouraging, thus promoting the design of more efficient and biocompatible systems. Research has focused on designing carriers to achieve biocompatibility, stability in the circulatory system, biodistribution to target the disease site, and intracellular delivery, all of which enhance the resulting therapeutic effect. The family of polyalkylene oxide PAO includes random, block and branched polymers, among which the ABA type triblocks copolymers of ethylene oxide EO and propylene oxide PO commercially known as Pluronic have received the greatest consideration. In this Account, we highlight examples of polycation-PAO conjugates, liposome-PAO formulations, and PAO micelles for nucleic acid delivery. Among the various polymer design consideration, which include molecular weight of polymer, molecular weight of blocks, and length of blocks, it has been found that the overall hydrophobic-lipophilic balance HLB is a critical parameter in defining the behavior of the polymer conjugates for gene delivery. The effects of varying this parameter are discussed in the context of improving gene delivery processes, such as serum stability and association with cell membranes.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research
- Polymer Chemistry