ABSTRACT
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.
Subject(s)
Albumins/metabolism , Antibodies/isolation & purification , Antibodies/metabolism , Drug Delivery Systems , Microspheres , Mucins/metabolism , Animals , Cross Reactions , Electrophoresis, Polyacrylamide Gel , Enzyme-Linked Immunosorbent Assay , Gastrointestinal Transit , Humans , Ileum/metabolism , Immunoglobulin G , Male , Mice , Rabbits , Rats , Rats, Wistar , Surface Properties , Swine , Time FactorsABSTRACT
Submicron sized hydrophobic and hydrophilic albumin microspheres (MS) were prepared using a chemical crosslinking technique. Spermine was linked to the surface of the hydrophilic MS. The degree of hydrophobicity for these three types of MS was investigated using a novel technique of sedimentation volume. The surface tension of the hydrophobic MS was 31 mN m-1. The ST of the hydrophilic MS was 68 mN m-1, whereas the surface tension of spermine-linked MS corresponded to 62, 65.5, 69 and 71 mN m-1 indicating heterogeneous hydrophilic characteristics. Ligands can be successfully linked to MS using a water-soluble carbodiimide.
