Al Lewis

Biocompatible polymer brushes grown from model quartz fibres: synthesis, characterisation and in situ determination of frictional coefficient

Poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC) chains were grown from near-monodisperse 13 µm diameter quartz fibres using surface-initiated atom transfer radical polymerisation (ATRP) at ambient temperature in 1 : 1 methanol–water at 20 °C. A covalently-bound siloxane-based ATRP initiator provided a sufficiently high grafting density to obtain polymer brushes from this model substrate. X-Ray photoelectron spectroscopy indicates that the PMPC brush coverage on this model fibre substrate is both thick and uniform, since the Si signals due to the underlying quartz are obscured. Thermogravimetric analysis (TGA) on selected PMPC-coated quartz fibres indicates a monotonic increase in PMPC brush thickness and reasonably good agreement was obtained with ellipsometry data, which was obtained indirectly for the corresponding PMPC brushes grown in situ from planar silicon wafers placed in the same reaction vessel as the quartz fibres. The dimensions of the thickest PMPC brush grown from the fibres could also be estimated by scanning electron microscopy. FT-IR spectroscopy confirmed a linear increase in the ester carbonyl band intensity for increasing target brush thickness, as expected. Rutherford back-scattering spectrometry (RBS) analyses also reported brush thicknesses that correlated linearly with this ester carbonyl band, but this technique appears to underestimate brush dimensions relative to TGA and ellipsometry. This is presumably due to in situ beam damage during RBS analysis. Friction force microscopy studies were conducted for both PMPC-coated and bare fibres immersed in water. Compared to the bare fibres, the presence of the PMPC chains led to a reduction in the relative frictional coefficient by more than an order of magnitude. A smaller, but still significant, reduction in the friction coefficient was also obtained using ethanol instead of water. This suggests possible applications for PMPC brushes in the context of aqueous lubrication.

Folate conjugated phosphorylcholine-based polycations for specific targeting in nucleic acids delivery

Folic acid has been investigated as a targeting ligand for imaging and therapeutic agent for over a decade; however, studies on its use in targeting of nonviral gene or nucleic acids delivery systems are sparse. This study assesses potential application of a new folic acid conjugate with aminomethacrylate–phosphoryl-choline based copolymer (DMAEMA-MPC–FA) as a targeting gene delivery vector. The folate-conjugated polymers produce colloidally stable polyplexes with a particle size <200 nm and demonstrate the ability to protect DNA from enzymatic degradation to a certain extent. In cells that overexpress folate receptors (MCF-7 and KB cultures), the conjugated systems show a folate-specific association and achieved significantly enhanced transfection efficiency, compared to the nonconjugated control, with a dramatically reduced nonspecific cellular association. The transfection enhancement is achieved without a corresponding increase in cellular association, suggesting that an internal cellular trafficking of folate-conjugated system may be altered, resulting in an increased transfection efficacy. In summary, a new folate-conjugated aminomethacrylate–phosphorylcholine copolymer is capable of forming colloidal complexes with DNA, modulating their specific cell uptake and improving the level of cell transfection in folate expressing cells.

pH-responsive nanoaggregation of diblock phosphorylcholine copolymers

We have characterized three diblock copolymers bearing zwitterionic phosphorylcholine and weak tertiary amine groups, namely, poly[((2-(methacryloyloxy)ethyl)phosphorylcholine)30- block-(2-(dimethylamino)ethyl methacrylate)60] (denoted as MPC30-DMA60, Mn=18,000), poly[((2-(methacryloyloxy)ethyl)phosphorylcholine)30- block-(2-(diethylamino)ethyl methacrylate)60) (denoted as MPC30-DEA60, Mn=20,000), and poly[((2-(methacryloyloxy)ethyl)phosphorylcholine)30- block-(2-(diisopropylamino)ethyl methacrylate)60) (denoted as MPC30-DPA60, Mn=21,000), by studying their surface tension and solution aggregation through a combined approach of surface tension measurement, dynamic light scattering, and small-angle neutron scattering. Our results show that larger tertiary amine substituents lead to an increasing tendency to form micellar aggregates, which is consistent with the increasing copolymer hydrophobicity. Thus, MPC30-DMA60 did not aggregate under the experimental conditions studied. The free chains exist in the form of thin cylinders, whose length decreases with copolymer concentration and solution temperature but increases with solution pH. The diameters of the MPC30-DMA60 cylinders remained almost constant at around 30 A under all the conditions studied. At the lower copolymer concentration of 0.5 wt %, the cylindrical lengths correspond to the persistence length of the copolymer backbone and are close to its full length, indicating a rather high rigidity. Further data analysis showed that, at the two higher concentrations of 2 and 4 wt %, the phosphorylcholine and amine blocks associate, inducing bending of the copolymer backbone. One backbone kink was required to satisfy all the constraints, including the dry volume of the copolymer. MPC30-DEA60 showed a similar trend of pH- and concentration-dependent conformational responses for the free copolymer, but in addition micellar aggregation occurred at pH 9. In contrast, MPC30-DPA60 exhibited significantly reduced solubility associated with strong aggregation, which is consistent with it being the most hydrophobic copolymer in the series.