Tissue affinity of the infusate affects the distribution volume during convection-enhanced delivery into rodent brains: Implications for local drug delivery

Ryuta Saito, Michal T. Krauze, Charles O. Noble, Matyas Tamas, Daryl C. Drummond, Dimitri B. Kirpotin, Mitchel S. Berger, John W. Park, Krystof S. Bankiewicz

研究成果: Article

75 引用 (Scopus)

抜粋

Convection-enhanced delivery (CED) is a recently developed technique for local delivery of agents to a large volume of tissue in the central nervous system (CNS). We have previously reported that this technique can be applied to CNS delivery of nanoparticles including viruses and liposomes. In this paper, we describe the impact of key physical and chemical properties of infused molecules on the extent of CED-mediated delivery. For simple infusates, CED distribution was significantly increased if the infusate was more hydrophilic or had less tissue affinity. Encapsulation of tissue-affinitive molecules by neutral liposomes significantly increased their tissue distribution. The poorer brain distribution observed with cationic liposomes, due to their greater tissue affinity, was completely overcome by PEGylation, which provides steric stabilization and reduced surface charge. Finally, liposomal encapsulation of doxorubicin reduced its tissue affinity and substantially increased its distribution within brain tumor tissue. Taken together, the physical and chemical properties of drugs, small molecules and macromolecular carriers determine the tissue affinity of the infusate and strongly affect the distribution of locally applied agents. Thus, an increased and more predictable tissue distribution can be achieved by reducing the tissue affinity of the infusate using appropriately engineered liposomes or other nanoparticles.

元の言語English
ページ(範囲)225-232
ページ数8
ジャーナルJournal of Neuroscience Methods
154
発行部数1-2
DOI
出版物ステータスPublished - 2006 6 30
外部発表Yes

ASJC Scopus subject areas

  • Neuroscience(all)

フィンガープリント Tissue affinity of the infusate affects the distribution volume during convection-enhanced delivery into rodent brains: Implications for local drug delivery' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用