Influence of physicochemical properties on pharmacokinetics of non-viral vectors for gene delivery.
The influence of physicochemical properties on the in vivo pharmacokinetics of gene delivery vectors after systemic administration is reviewed based on our studies. We have been studying the development of DNA delivery systems, such as plasmid DNA complexed with cationic polymers (polyplexes) and cationic liposomes (lipoplexes). Even if target-recognizable ligand is incorporated into the system, the overall physicochemical properties, notably size and charge, are predominant factors influencing in vivo disposition characteristics of the vector. Based on this consideration, liver cell-specific carrier systems via receptor-mediated endocytosis were successfully developed by optimizing physicochemical characteristics. In conclusion, rational design of gene delivery vectors requires an understanding of their pharmacokinetics in relation to the physicochemical properties. Optimization of the physicochemical properties is important for successful in vivo gene delivery by non-viral vectors.
Takakura
Yoshinobu
Y
Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
Nishikawa
Makiya
M
Yamashita
Fumiyoshi
F
Hashida
Mitsuru
M
D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004269:DNA, Bacterial / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage / Q000493:pharmacokinetics
D004269:DNA, Bacterial; D008081:Liposomes