Targeted polymers for gene delivery.
Over the past decade, significant research has been done in the area of polymer-mediated gene delivery. Synthesis of new polymers and modifications to existing polymers has resulted in polyplexes with improved in vitro and in vivo transfection efficiencies. Targeting has been an important aspect of this research, and various strategies for obtaining selective and enhanced gene delivery to the target site have been evaluated. This review covers the different aspects involved in polyplex targeting. Development of targeted polyplexes involves a careful consideration of the target site, the targeting ligand and the physicochemical properties of the polyplex itself. The need to redirect the polyplexes by using the 'shield and target' approach by reducing nonspecific interactions with negatively charged components, while conferring specificity by incorporating targeting ligands, is discussed. Basic chemistry involved in modifying polymers is covered and examples of targeting strategies used for tissue-specific gene delivery are discussed. Targeting is also discussed in the broader context of developing safe and effective polymeric vectors for in vivo gene delivery. Maximum benefit of targeting can be obtained when it is used as part of a multi-functional complex containing elements designed to improve gene delivery and reduce overall toxicity of the polyplex.
Hughes
Jeffery A
JA
University of Florida, Department of Pharmaceutics, College of Pharmacy, Gainesville, Florida, USA.
Rao
Gururaj A
GA
D000818:Animals; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D008024:Ligands; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D011108:Polymers / Q000737:chemistry; D013499:Surface Properties
D008024:Ligands; D011108:Polymers; D004247:DNA