6533b82dfe1ef96bd1291567

RESEARCH PRODUCT

Synthesis of Novel Folic Acid-Functionalized Biocompatible Block Copolymers by Atom Transfer Radical Polymerization for Gene Delivery and Encapsulation of Hydrophobic Drugs

S. P. ArmesYiqing TangAndrew L. LewisNorman C. BillinghamMariano Licciardi

subject

Polymers and PlasticsTertiary aminePolymersDrug CompoundingBiocompatible MaterialsBioengineeringChloroformateConjugated systemMethacrylateBiomaterialschemistry.chemical_compoundFolic AcidPolymer chemistryMaterials ChemistryCopolymerPOLYMER SYNTHESIS ATRPDrug CarriersMolecular StructureAtom-transfer radical-polymerizationGenetic TherapyHydrogen-Ion ConcentrationEnd-groupchemistrySettore CHIM/09 - Farmaceutico Tecnologico ApplicativoDrug carrierHydrophobic and Hydrophilic Interactions

description

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.

yearjournalcountryeditionlanguage
2005-03-15Biomacromolecules
https://doi.org/10.1021/bm049271i