Synthesis of novel folic acid-functionalized biocompatible block copolymers by atom transfer radical polymerization for gene delivery and encapsulation of hydrophobic drugs.
Two synthetic routes to folic acid (FA)-functionalized diblock copolymers based on 2-(methacryloyloxy)ethyl phosphorylcholine [MPC] and either 2-(dimethylamino)ethyl methacrylate [DMA] or 2-(diisopropylamino)ethyl methacrylate [DPA] were explored. The most successful route involved atom transfer radical polymerization (ATRP) of MPC followed by the tertiary amine methacrylate using a 9-fluorenylmethyl chloroformate (Fmoc)-protected ATRP initiator. Deprotection of the Fmoc groups produced terminal primary amine groups, which were conjugated with FA to produce two series of novel FA-functionalized biocompatible block copolymers. Nonfunctionalized MPC-DMA diblock copolymers have been previously shown to be effective synthetic vectors for DNA condensation; thus, these FA-functionalized MPC-DMA diblock copolymers appear to be well suited to gene therapy applications based on cell targeting strategies. In contrast, the FA-MPC-DPA copolymers are currently being evaluated as pH-responsive micellar vehicles for the delivery of highly hydrophobic anticancer drugs.
Licciardi
M
M
Department of Chemistry, University of Sussex, Falmer, Brighton, BN1 9QJ East Sussex, United Kingdom. m.licciardi@unipa.it
Tang
Y
Y
Billingham
N C
NC
Armes
S P
SP
Lewis
A L
AL
D001672:Biocompatible Materials / Q000138:chemical synthesis*; D004337:Drug Carriers / Q000138:chemical synthesis*; D004339:Drug Compounding; D005492:Folic Acid; D015316:Genetic Therapy; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D015394:Molecular Structure; D011108:Polymers / Q000138:chemical synthesis* / Q000627:therapeutic use
D001672:Biocompatible Materials; D004337:Drug Carriers; D011108:Polymers; D005492:Folic Acid