Design and evaluation of thin and flexible theophylline imprinted polymer membrane materials.

The aim of this work was to produce a thin, flexible and diffusion able molecularly imprinted polymeric matrix with good template accessibility. Membranes were prepared using a non-covalent molecular imprinting approach and their physical characteristics and binding capabilities investigated. Two materials were used, a poly(tri-ethyleneglycol dimethyacrylate-co-methyl methacrylate-co-methacrylic acid) copolymer containing 14% cross-linker and a monomer (g) to porogen (ml) ratio of 1:0.5 (A), and a blend of poly(TEGMA-co-MAA) and polyurethane (B). The polyurethane was added to improve membrane flexiblity and stability. The polymers were characterized using AFM, SEM and nitrogen adsorption, whilst binding was evaluated using batch-rebinding studies. For all membranes the specific surface area was low (<10 m(2)/g). MIP (A) films were shown to bind specifically at low concentrations but specific binding was masked by non-specific interactions at elevated concentrations. Selectivity studies confirmed specificity at low concentrations. K(D) approximations confirmed a difference in the population of binding sites within NIP and MIP films. The data also indicated that at low concentrations the ligand-occupied binding site population approached homogeneity. Scanning electron microscopy images of membrane (B) revealed a complex multi-layered system, however these membranes did not demonstrate specificity for the template. The results described here demonstrate how the fundamental parameters of a non-covalent molecularly imprinted system can be successfully modified in order to generate flexible and physically tolerant molecularly imprinted thin films.

Concentration dependent atrazine-atrazine complex formation promotes selectivity in atrazine imprinted polymers.

An atrazine (ATR) molecularly imprinted polymer (MIP) was prepared using a non-covalent strategy. The affinity and selectivity of the polymer was initially evaluated under non-equilibrium conditions and the polymer was shown to possess good template selectivity. The selectivity of the polymer was further investigated under equilibrium conditions and over a range of concentrations using Scatchard plots and Hill plots and by assessing distribution coefficients and normalised selectivity values. It was observed that both selectivity and affinity were dependent on the concentration of the ligand and that unusually selectivity and affinity were better at higher atrazine concentrations. It was concluded that this phenomenon resulted from the formation of atrazine-atrazine complexes during the pre-polymerisation stage and during rebinding and that the polymer demonstrated improved atrazine affinity when the conditions favoured complex formation.

From 3D to 2D: a review of the molecular imprinting of proteins.

Molecular imprinting is a generic technology that allows for the introduction of sites of specific molecular affinity into otherwise homogeneous polymeric matrices. Commonly this technique has been shown to be effective when targeting small molecules of molecular weight <1500, while extending the technique to larger molecules such as proteins has proven difficult. A number of key inherent problems in protein imprinting have been identified, including permanent entrapment, poor mass transfer, denaturation, and heterogeneity in binding pocket affinity, which have been addressed using a variety of approaches. This review focuses on protein imprinting in its various forms, ranging from conventional bulk techniques to novel thin film and monolayer surface imprinting approaches.

Skin permeation and ex vivo skin metabolism of O-acyl haloperidol ester prodrugs.

Ethyl (HE), propyl (HP), butyl (HB), octyl (HO) and decyl (HD) O-acyl esters of haloperidol (HA) were evaluated for permeation across full-thickness human and guinea pig skin. The inclusion of 0.5mgmL(-1) cetrimide as a receptor phase solubilising agent did not significantly alter the barrier properties of the membranes. The permeation of the parent drug, HA, across guinea pig skin was found to be greater than that of its derivatives. Prodrug hydrolysis by cutaneous esterases was minimal. The permeation of HE, HP and HB across freshly excised guinea pig skin was subsequently investigated, however, prodrug hydrolysis remained low. Hydrolysis studies using a skin extract revealed only limited prodrug metabolism. However, in the presence of a liver extract, hydrolysis of all prodrugs was rapid. It was proposed that GGGX esterases, required for the hydrolysis of tertiary esters, were not present at a sufficiently high concentration within the skin for substantial prodrug hydrolysis to occur. This does not necessarily detract from the system as post-transdermal delivery liberation of HA in vivo is an equally useful mode for delivering this drug to the systemic circulation.

Synthesis of haloperidol prodrugs and their hydrolysis by porcine liver esterase.

In probing enhancement of the transdermal delivery of the anti-psychotic drug haloperidol, five prodrugs (ethanoate, propanoate, butanoate, octanoate and decanoate) were synthesised and their relative rates of hydrolysis determined in the presence of porcine liver esterase (PLE), a model for cutaneous esterases. (1)H NMR, MS and elemental analysis confirmed the successful synthesis of each prodrug in high purity, and each was found to hydrolyse in the presence of PLE with the hydrolytic rate reaching a maximum with haloperidol octanoate (C8) at 2.31 +/- 0.06 nmol ml(-1) h(-1) (p < 0.001).