Angela Macadam

The effect of gastro-intestinal mucus on drug absorption

Abstract The layer of mucus covering the gastro-intestinal tract has a number of important functions. For example, it provides an unstirred buffering layer adjacent to the mucosal epithelium which protects the underlying membrane from the corrosive elements in the luminal content. Also as a visco-elastic gel, it aids the passage of food over the epithelium, thereby limiting potential erosive damage. The mucus layer is composed mainly of water, but it is the high-molecular-weight glycoprotein component which is responsible for gel formation. Differences in glycoprotein structure can impart varying properties to the mucus gel and attempts have been made to characterise mucus, especially changes which occur in disease states, by both histological and biochemical means. The mucus layer in addition to affording protection is also a potential barrier to drug absorption. Mucus has been shown to retard the diffusion of hydrogen ions when compared with an equivalent thickness of water. Specific drugs have been demonstrated to bind to mucus glycoprotein, thereby reducing the diffusion coefficient. There has been much current interest in the use of bioadhesive formulations and specific binding ligands with the view to decreasing the distance a drug must diffuse through the luminal contents in order to reach the mucosal epithelium. The high rates of mucus turnover may limit the exploitation of such devices within the gastro-intestinal tract.

Preparation of hydrophobic and hydrophilic albumin microspheres and determination of surface carboxylic acid and amino residues

Abstract Albumin microspheres (MS) have been studied extensively as delivery systems for targeting drugs since they are biodegradable, non-toxic, relatively easy to prepare and their size range can be controlled. A method for albumin MS production was developed which was faster, processed larger quantities of starting material than previous methods, and had chemically reactive groupings on the MS surface to which ligands could be attached. Relatively hydrophobic, hydrophilic and also carboxymethylated MS were manufactured. The number of carboxylic acid residues was determined on the surface of these MS using 14 C-glycine ethyl ester hydrochloride as a probe, and the number of amino groups was determined using 14 C-sodium acetate as a probe. The number of carboxylic acid residues per unit surface area for the hydrophobic, hydrophilic and carboxymethylated MS was 2.1 × 10 4 , 4.1 × 10 4 and 8.4 × 10 4 , respectively, and the number of amino acid residues was 2.2 × 10 3 , 5.0 × 10 2 and 5.0 × 10 2 , respectively

Medication Errors in Community Pharmacy: an investigation into the types and potential causes

Objectives To establish the nature of medication errors occurring within community pharmacy and analyse common error patterns. To identify factors which influence the occurrence of medication errors and near misses, with the intention of designing systems or strategies to reduce the occurrence of these events.

Anti-mucus polyclonal antibody production, purification and linkage to the surface of albumin microspheres

This aim of this study was to develop a microparticulate based oral drug delivery system, which could prolong gut transit time by binding via specific interactions to the gut mucus layer. Porcine gastric mucus was semi-purified and used as an antigen to raise a polyclonal antiserum in rabbits. The immunoglobulin fraction of this serum was isolated, purified and tested for homogeneity and cross reactivity. High cross-reactivity was displayed when the antiserum was challenged against types of mucus other than that used as an antigen, but no significant cross-reactivity occurred when challenged against some other common macromolecules. The antibody fraction of this serum was covalently linked to three types of albumin microspheres (MS) using 1-ethyl-3(3-dimethyl aminopropyl) carbodiimide. The MS employed had either a hydrophobic, a hydrophilic or a carboxymethylated surface, and were prepared and characterised as described earlier (MacAdam, A.B., Shafi, Z.B., Martin, G.P. and James, S.L. 1997. Preparation of hydrophobic and hydrophilic MS and determination of surface carboxylic acid and amino residues. Int. J. Pharm. 151, 47-55). Binding of these MS to both radioiodinated mucin in suspension and to isolated gut segments was measured. Hydrophilic and carboxymethylated MS with surface-associated antibody bound significantly more mucin from a suspension than did uncoated controls. Similarly, anti-mucus antibody-coated hydrophilic and carboxymethylated MS bound more strongly to an isolated gut segment than did uncoated controls or controls coated in an antibody specific for albumin. These results suggest anti-mucus antibody coated albumin MS may be a useful model to act as comparators in studies aimed at developing drug delivery systems with delayed gastrointestinal transit.

The potential role of the sodium iodide symporter gene polymorphism in the development of differentiated thyroid cancer

The sodium iodide symporter (NIS) (solute carrier family 5; SLC5A), mediates the active transport of iodine anion (I(-)) into thyroid follicular cells to facilitate thyroid hormone biosynthesis. Considering its fundamental role in thyroid function, our objective in this study is to explore its potential involvement in the pathogenesis of differentiated thyroid cancer (DTC). Following a preliminary sequencing of the gene in a representative sample of the general population, five variants, (1) rs45602038, (2) rs4808708, (3) rs4808709, (4) rs7250346 and (5) rs12327843, were selected for a larger population-based association study consisting of 507 cases and 597 controls, of which only the rs45602038_TT [Odds ratio (95% confidence interval)=1.90 (1.26-2.88); p=0.002] was associated with disease following adjustment for other confounders using the multivariate analysis. Furthermore, a 5-mer haplotype CGAGT constructed from the five studied SNPs conferred a significant risk (χ(2)=10.98; p=0.0009) for DTC. This association trickled down through shorter derivatives, with the 4-mer haplotype CGAG (χ(2)=13.25; p=0.0003) displaying the most significant association and the 3-mer GAG (χ(2)=11.80; p=0.0006) being equally strongly linked to the disease. Comparison of the flanking derivatives of the primary 5-mer haplotype also indicated that the 3-mer CGA (χ(2)=4.04; p=0.045) constructed from SNP block 1-3 was a lot weaker than that of the AGT (χ(2)=6.73; p=0.0095) constructed from the blocks 3-5 from the other end of the gene. Put together, these data implicate the three nucleotide changes at the rs4808708, rs4808709 and rs7250346 loci (blocks 2-4) as the core for this relationship.

Knowledge and beliefs of young people about medicines in the UK.

To investigate knowledge and beliefs regarding medicines among young people in the South‐East of England.