Biodegradable polymer matrices for the sustained exogenous delivery of a biologically active c-myc hammerhead ribozyme☆
作者： Andrew J. Hudson , Karen J. Lewis , M.Vaman Rao , Saghir Akhtar
DOI: 10.1016/0378-5173(96)04474-2
关键词:
摘要: Abstract Ribozymes are potent RNA molecules that can inhibit gene expression in a sequence-specific manner by catalysing the trans-cleavage of target mRNA. The ‘hammerhead’ motif is most widely studied ribozyme and currently being developed as potential therapeutic agent for cancers viral diseases. However, poor biological stability chemistries typically requires repeated exogenous administration ribozymes long-term effects. In this study, we have evaluated use biodegradable poly-(L-lactic acid) (PLA) polymer matrices to improve provide sustained delivery biologically active hammerhead designed cleave mRNA c- myc proto-oncogene. vitro release profile showed entrapped was released biphasically from films, characterised an initial rapid burst release, followed more over period several weeks. Release dependent on loading but similar DNA oligonucleotides same length. entrapment within solvent cast PLA film improved its serum seconds (for ‘free’ ribozyme) than 2 weeks when matrices. catalytic cleavage activity polymer-released identical suggesting device fabrication procedure did not adversely affect hybridization properties ribozyme. These data suggest devices appear suitable worthy further investigation.
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