Synthesis of amphiphilic hyperbranched glyco-polydendrons for potential applications in nanomedicine

• Main Author: Dwyer, A. B.
• Published: University of Liverpool 2016
• Subjects: 610.28
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.706771

The synthesis of amphiphilic hyperbranched glycopolydendrons bearing multivalent surface functionalities has yielded materials with potential nanomedical drug-delivery applications that may also be capable of actively targeting disease sites. The development of the hydrophilic surface functionalities (based on PEG, galactose and mannose moieties) and hydrophobic core functionalities (based on poly(n-butyl methacrylate)) are presented. Despite methanol (MeOH) being widely regarded as an antisolvent for p(nBuMA), Cu-catalysed ATRP of nBuMA has been performed utilising anhydrous MeOH as the reaction solvent. Successful polymerisation was achieved at 60 °C and 25 °C using ethyl 2-bromoisobutyrate as the initiator, yielding well-defined polymers with high molecular weights (up to Mn = 75 880 g mol-1) and low dispersities (as low as D = 1.02). The effect of monomer co-solvency was investigated by determining the cloud point behaviour (upper critical solution temperature) of p(nBuMA) within the methanolic environment, and the effect of the ligand on the control of the polymerisation was also investigated. Successful polymerisation was also extended to RAFT, yielding low dispersity polymers that were analogous to those obtained by ATRP. The methanolic polymerisation by Cu-catalysed ATRP was utilised to exploit the hydrophobic nature of p(nBuMA) as the core functionality of amphiphilic branched copolymer nanoparticles bearing PEG surface functionalities. The nanoparticles were prepared via a rapid nanoprecipitation approach, however, their small hydrodynamic diameters (Dn = 17 nm-27 nm) suggested nanoparticle formation by a solvent-switch rather than a nucleation/growth mechanism that is normally associated with this technique. Dendritic ATRP initiators bearing multivalent protected galactose functionalities, also varying in generation number, were obtained by aza-Michael-type additions and used within the branched methanolic ATRP of nBuMA. Deprotection of the isopropylidene protecting groups was achieved under acidic reaction conditions using para-toluene sulfonic acid monohydrate; nanoprecipitation of the resulting galactosylated hypglycopolydendrons yielded charge-stabilised nanoparticles with Dz = 43-46 nm and highly negative zeta potentials. Comparisons to their protected equivalents were made.